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idK151917_s0_e2000

K151917.txt

product code

OOI – Real-time nucleic acid amplification

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY INSTRUMENT ONLY TEMPLATE A. 510(k) Number: k151917 B. Purpose for Submission: New instrument for use with the ARIES® HSV 1&2 Assay cleared under k151906 C. Manufacturer and Instrument Name: Luminex Corporation, ARIES® System D. Type of Test or Tests Performed: Nucleic-acid amplification testing E. System Descriptions: 1. Device Description: The ARIES® System is a clinical multiplex test system that automates and integrates extraction of nucleic acid from a clinical sample, performs real -time PCR, and measuring and sorting multiple signals generated in an in vitro diagnostic assay. The instrument system is used with specific IVD assays to measure multiple analytes. The device includes a signal reader unit, raw data storage mechanisms, data acquisition software and software to process detected signals. The ARIES® System is for in vitro diagnostic use by trained laboratory professionals in a controlled laboratory environment and is not intended for patient contact. The ARIES® System consists of the following; · a bench top instrument with two separate modules each with a magazine rack to accommodate six disposable single-use assay cassettes · methods for manipulating sample and reagent movement within the cassette · heaters for lysis, elution and nucleic acid amplification · 6 optical channels · fluorometer for real-time PCR fluorescence detection and melt analysis · methods for thermal and optical calibration · software for running and analyzing IVD assays 2. Principles of Operation: a. Device Features Controlled by Software: 2 The ARIES® SYSTEM instrument uses the ARIES® Software 1.0 software and the ARIES® Assay Protocol file for data acquisition, analysis, and reporting. The ARIES® instrument software is installed on the embedded PC and controls the two modules housed in the instrument. The ARIES® Instrument is a Real Time PCR Instrument. The ARIES® instrument software provides the interface between the ARIES® Software 1.0 and the ARIES® system hardware. The ARIES® system software communicates to the instrument software to manage operations of the system, including manipulation of sample and reagent movement within the cassette, control of heaters for lysis, elution and nucleic acid amplification, controlling the fluorimeter for real-time PCR bulk fluorescence detection and melt analysis, controlling thermal and optical calibration and data analysis for IVD assays run on the system. The ARIES® Software 1.0 software is installed in an embedded computer and provides the graphical user interface (GUI) application that is intended to be the end- user interface to the ARIES® instrument. The ARIES® Software 1.0 software is responsible for providing the environment in which an end-user runs and reports assays, administers, maintains, and sets default settings for the system. The ARIES® Assay Protocol Software is a framework that allows running assays and generating reports on an ARIES® instrument. The ARIES® Assay Protocol Software is contained within an assay protocol template. This template is a read-only type of assay protocol file that contains a specific script, data reduction, assay editor tool, and reports, and default assay parameters and blank call logic. The ARIES® Assay Protocol file that is generated contains assay logic (rules that specify clinical outcomes), data reduction runtime files (DLL), and assay configuration parameters (script parameters that control the instrument for running a sample in a cassette and data reduction algorithm parameters). b. Operational Environment (Off-the-Shelf Software): The ARIES® Software 1.0 software uses some commercial off-the-shelf software components. The sponsor provided detailed documentation for the OTS used, including validation, for both the ARIES® Software 1.0 software and the ARIES® Assay Protocol Software. For the ARIES® Assay Protocol Software used by Luminex, the recommended configuration for each computer is: • Windows 7 Professional SP1 (US English, 32 bit or 64 bit) • 2.8 GHz Intel Dual Core (or higher) • 4 Gb RAM (or higher) • 160 GB hard drive (or higher) The programming language used to develop the ARIES® Software 1.0 software was 3 Microsoft Visual C#. Instrument control software was written in a combination and C# and C++. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___x_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___x_____ 4. Specimen Identification: A barcode reader may be used for entry of sample IDs, or they may be entered manually. 5. Specimen Sampling and Handling: Samples are manually prepared according to assay manufacturer’s suggestions and are transferred to an assay specific cassette for analysis. 6. Calibration: Calibration is performed by Luminex service personnel using ARIES® System Verification Cassettes. 7. Quality Control: Each ARIES® assay cassette includes a Sample Process Control (SPC). The SPC has a known melting temperature (Tm) range and cycle threshold (Ct) range. Each time an assay is run, the system measures the temperature and fluorescence intensity of the SPC control to ensure the thermal and optical subsystems have remained in calibration. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes_____x___ or No________ 4 F. Regulatory Information: 1. Regulation section: 21 CFR 862.2570 Instrumentation for clinical multiplex test systems 2. Classification: Class II (special controls) 3 Product code: OOI – Real-time nucleic acid amplification 4. Panel: Chemistry (75) G. Intended Use: 1. Indication(s) for Use: The Luminex ARIES® System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: BD Diagnostics (Becton, Dickinson and Company), BD MAX System K111860 2. Comparison with Predicate Device: Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Intended Use The Luminex ARIES® System is an in vitro Same 5 Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence- based PCR. Sample Preparation Method Automated nucleic acid lysis and extraction by the ARIES® system Same Assay Format Amplification: Real Time PCR Detection: Fluorgenic Same Interpretation of Test Results Automated (Diagnostic software of Luminex ARIES® System) Same Differences Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Fluidics Self-contained Manual sample preparation Assay Cartridge · Cartridge is closed to the environment · Single Use · Reagent strips are open to the environment · Can be used twice Fluorescence Channels Six (6) channels Five (5) channels Software Software resides on the ARIES® System Software resides on an all- in-one computer I. Special Control/Guidance Document Referenced (if applicable): · IEC60825 – Safety of laser products, 2nd edition, 2007 · IEC62304, - Medical Device Software – Software Life Cycle Processes, 2006 · ISO 14971 – Medical Devices – Applications of Risk Management, 2007 · ISO15223-1 – Medical Devices – Symbols to be used with Medical Device Labels, Labelling, and Information to be Supplied, 2007 6 J. Performance Characteristics: 1. Analytical Performance: Performance for the ARIES® System was established in the clearance of the assay, the ARIES® HSV1&2 Assay (k151906). a. Accuracy: See k151906 b. Precision/Reproducibility: See k151906 c. Linearity: See k151906 d. Carryover: See k151906 e. Interfering Substances: See k151906 2. Other Supportive Instrument Performance Data Not Covered Above: Not applicable K. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Product code:

idK151917_s0_e2000

K151917.txt

panel

Chemistry (75)

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY INSTRUMENT ONLY TEMPLATE A. 510(k) Number: k151917 B. Purpose for Submission: New instrument for use with the ARIES® HSV 1&2 Assay cleared under k151906 C. Manufacturer and Instrument Name: Luminex Corporation, ARIES® System D. Type of Test or Tests Performed: Nucleic-acid amplification testing E. System Descriptions: 1. Device Description: The ARIES® System is a clinical multiplex test system that automates and integrates extraction of nucleic acid from a clinical sample, performs real -time PCR, and measuring and sorting multiple signals generated in an in vitro diagnostic assay. The instrument system is used with specific IVD assays to measure multiple analytes. The device includes a signal reader unit, raw data storage mechanisms, data acquisition software and software to process detected signals. The ARIES® System is for in vitro diagnostic use by trained laboratory professionals in a controlled laboratory environment and is not intended for patient contact. The ARIES® System consists of the following; · a bench top instrument with two separate modules each with a magazine rack to accommodate six disposable single-use assay cassettes · methods for manipulating sample and reagent movement within the cassette · heaters for lysis, elution and nucleic acid amplification · 6 optical channels · fluorometer for real-time PCR fluorescence detection and melt analysis · methods for thermal and optical calibration · software for running and analyzing IVD assays 2. Principles of Operation: a. Device Features Controlled by Software: 2 The ARIES® SYSTEM instrument uses the ARIES® Software 1.0 software and the ARIES® Assay Protocol file for data acquisition, analysis, and reporting. The ARIES® instrument software is installed on the embedded PC and controls the two modules housed in the instrument. The ARIES® Instrument is a Real Time PCR Instrument. The ARIES® instrument software provides the interface between the ARIES® Software 1.0 and the ARIES® system hardware. The ARIES® system software communicates to the instrument software to manage operations of the system, including manipulation of sample and reagent movement within the cassette, control of heaters for lysis, elution and nucleic acid amplification, controlling the fluorimeter for real-time PCR bulk fluorescence detection and melt analysis, controlling thermal and optical calibration and data analysis for IVD assays run on the system. The ARIES® Software 1.0 software is installed in an embedded computer and provides the graphical user interface (GUI) application that is intended to be the end- user interface to the ARIES® instrument. The ARIES® Software 1.0 software is responsible for providing the environment in which an end-user runs and reports assays, administers, maintains, and sets default settings for the system. The ARIES® Assay Protocol Software is a framework that allows running assays and generating reports on an ARIES® instrument. The ARIES® Assay Protocol Software is contained within an assay protocol template. This template is a read-only type of assay protocol file that contains a specific script, data reduction, assay editor tool, and reports, and default assay parameters and blank call logic. The ARIES® Assay Protocol file that is generated contains assay logic (rules that specify clinical outcomes), data reduction runtime files (DLL), and assay configuration parameters (script parameters that control the instrument for running a sample in a cassette and data reduction algorithm parameters). b. Operational Environment (Off-the-Shelf Software): The ARIES® Software 1.0 software uses some commercial off-the-shelf software components. The sponsor provided detailed documentation for the OTS used, including validation, for both the ARIES® Software 1.0 software and the ARIES® Assay Protocol Software. For the ARIES® Assay Protocol Software used by Luminex, the recommended configuration for each computer is: • Windows 7 Professional SP1 (US English, 32 bit or 64 bit) • 2.8 GHz Intel Dual Core (or higher) • 4 Gb RAM (or higher) • 160 GB hard drive (or higher) The programming language used to develop the ARIES® Software 1.0 software was 3 Microsoft Visual C#. Instrument control software was written in a combination and C# and C++. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___x_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___x_____ 4. Specimen Identification: A barcode reader may be used for entry of sample IDs, or they may be entered manually. 5. Specimen Sampling and Handling: Samples are manually prepared according to assay manufacturer’s suggestions and are transferred to an assay specific cassette for analysis. 6. Calibration: Calibration is performed by Luminex service personnel using ARIES® System Verification Cassettes. 7. Quality Control: Each ARIES® assay cassette includes a Sample Process Control (SPC). The SPC has a known melting temperature (Tm) range and cycle threshold (Ct) range. Each time an assay is run, the system measures the temperature and fluorescence intensity of the SPC control to ensure the thermal and optical subsystems have remained in calibration. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes_____x___ or No________ 4 F. Regulatory Information: 1. Regulation section: 21 CFR 862.2570 Instrumentation for clinical multiplex test systems 2. Classification: Class II (special controls) 3 Product code: OOI – Real-time nucleic acid amplification 4. Panel: Chemistry (75) G. Intended Use: 1. Indication(s) for Use: The Luminex ARIES® System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: BD Diagnostics (Becton, Dickinson and Company), BD MAX System K111860 2. Comparison with Predicate Device: Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Intended Use The Luminex ARIES® System is an in vitro Same 5 Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence- based PCR. Sample Preparation Method Automated nucleic acid lysis and extraction by the ARIES® system Same Assay Format Amplification: Real Time PCR Detection: Fluorgenic Same Interpretation of Test Results Automated (Diagnostic software of Luminex ARIES® System) Same Differences Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Fluidics Self-contained Manual sample preparation Assay Cartridge · Cartridge is closed to the environment · Single Use · Reagent strips are open to the environment · Can be used twice Fluorescence Channels Six (6) channels Five (5) channels Software Software resides on the ARIES® System Software resides on an all- in-one computer I. Special Control/Guidance Document Referenced (if applicable): · IEC60825 – Safety of laser products, 2nd edition, 2007 · IEC62304, - Medical Device Software – Software Life Cycle Processes, 2006 · ISO 14971 – Medical Devices – Applications of Risk Management, 2007 · ISO15223-1 – Medical Devices – Symbols to be used with Medical Device Labels, Labelling, and Information to be Supplied, 2007 6 J. Performance Characteristics: 1. Analytical Performance: Performance for the ARIES® System was established in the clearance of the assay, the ARIES® HSV1&2 Assay (k151906). a. Accuracy: See k151906 b. Precision/Reproducibility: See k151906 c. Linearity: See k151906 d. Carryover: See k151906 e. Interfering Substances: See k151906 2. Other Supportive Instrument Performance Data Not Covered Above: Not applicable K. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Panel:

idK151917_s0_e2000

K151917.txt

predicate device name

BD Diagnostics (Becton, Dickinson and Company), BD MAX System

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY INSTRUMENT ONLY TEMPLATE A. 510(k) Number: k151917 B. Purpose for Submission: New instrument for use with the ARIES® HSV 1&2 Assay cleared under k151906 C. Manufacturer and Instrument Name: Luminex Corporation, ARIES® System D. Type of Test or Tests Performed: Nucleic-acid amplification testing E. System Descriptions: 1. Device Description: The ARIES® System is a clinical multiplex test system that automates and integrates extraction of nucleic acid from a clinical sample, performs real -time PCR, and measuring and sorting multiple signals generated in an in vitro diagnostic assay. The instrument system is used with specific IVD assays to measure multiple analytes. The device includes a signal reader unit, raw data storage mechanisms, data acquisition software and software to process detected signals. The ARIES® System is for in vitro diagnostic use by trained laboratory professionals in a controlled laboratory environment and is not intended for patient contact. The ARIES® System consists of the following; · a bench top instrument with two separate modules each with a magazine rack to accommodate six disposable single-use assay cassettes · methods for manipulating sample and reagent movement within the cassette · heaters for lysis, elution and nucleic acid amplification · 6 optical channels · fluorometer for real-time PCR fluorescence detection and melt analysis · methods for thermal and optical calibration · software for running and analyzing IVD assays 2. Principles of Operation: a. Device Features Controlled by Software: 2 The ARIES® SYSTEM instrument uses the ARIES® Software 1.0 software and the ARIES® Assay Protocol file for data acquisition, analysis, and reporting. The ARIES® instrument software is installed on the embedded PC and controls the two modules housed in the instrument. The ARIES® Instrument is a Real Time PCR Instrument. The ARIES® instrument software provides the interface between the ARIES® Software 1.0 and the ARIES® system hardware. The ARIES® system software communicates to the instrument software to manage operations of the system, including manipulation of sample and reagent movement within the cassette, control of heaters for lysis, elution and nucleic acid amplification, controlling the fluorimeter for real-time PCR bulk fluorescence detection and melt analysis, controlling thermal and optical calibration and data analysis for IVD assays run on the system. The ARIES® Software 1.0 software is installed in an embedded computer and provides the graphical user interface (GUI) application that is intended to be the end- user interface to the ARIES® instrument. The ARIES® Software 1.0 software is responsible for providing the environment in which an end-user runs and reports assays, administers, maintains, and sets default settings for the system. The ARIES® Assay Protocol Software is a framework that allows running assays and generating reports on an ARIES® instrument. The ARIES® Assay Protocol Software is contained within an assay protocol template. This template is a read-only type of assay protocol file that contains a specific script, data reduction, assay editor tool, and reports, and default assay parameters and blank call logic. The ARIES® Assay Protocol file that is generated contains assay logic (rules that specify clinical outcomes), data reduction runtime files (DLL), and assay configuration parameters (script parameters that control the instrument for running a sample in a cassette and data reduction algorithm parameters). b. Operational Environment (Off-the-Shelf Software): The ARIES® Software 1.0 software uses some commercial off-the-shelf software components. The sponsor provided detailed documentation for the OTS used, including validation, for both the ARIES® Software 1.0 software and the ARIES® Assay Protocol Software. For the ARIES® Assay Protocol Software used by Luminex, the recommended configuration for each computer is: • Windows 7 Professional SP1 (US English, 32 bit or 64 bit) • 2.8 GHz Intel Dual Core (or higher) • 4 Gb RAM (or higher) • 160 GB hard drive (or higher) The programming language used to develop the ARIES® Software 1.0 software was 3 Microsoft Visual C#. Instrument control software was written in a combination and C# and C++. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___x_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___x_____ 4. Specimen Identification: A barcode reader may be used for entry of sample IDs, or they may be entered manually. 5. Specimen Sampling and Handling: Samples are manually prepared according to assay manufacturer’s suggestions and are transferred to an assay specific cassette for analysis. 6. Calibration: Calibration is performed by Luminex service personnel using ARIES® System Verification Cassettes. 7. Quality Control: Each ARIES® assay cassette includes a Sample Process Control (SPC). The SPC has a known melting temperature (Tm) range and cycle threshold (Ct) range. Each time an assay is run, the system measures the temperature and fluorescence intensity of the SPC control to ensure the thermal and optical subsystems have remained in calibration. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes_____x___ or No________ 4 F. Regulatory Information: 1. Regulation section: 21 CFR 862.2570 Instrumentation for clinical multiplex test systems 2. Classification: Class II (special controls) 3 Product code: OOI – Real-time nucleic acid amplification 4. Panel: Chemistry (75) G. Intended Use: 1. Indication(s) for Use: The Luminex ARIES® System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: BD Diagnostics (Becton, Dickinson and Company), BD MAX System K111860 2. Comparison with Predicate Device: Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Intended Use The Luminex ARIES® System is an in vitro Same 5 Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence- based PCR. Sample Preparation Method Automated nucleic acid lysis and extraction by the ARIES® system Same Assay Format Amplification: Real Time PCR Detection: Fluorgenic Same Interpretation of Test Results Automated (Diagnostic software of Luminex ARIES® System) Same Differences Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Fluidics Self-contained Manual sample preparation Assay Cartridge · Cartridge is closed to the environment · Single Use · Reagent strips are open to the environment · Can be used twice Fluorescence Channels Six (6) channels Five (5) channels Software Software resides on the ARIES® System Software resides on an all- in-one computer I. Special Control/Guidance Document Referenced (if applicable): · IEC60825 – Safety of laser products, 2nd edition, 2007 · IEC62304, - Medical Device Software – Software Life Cycle Processes, 2006 · ISO 14971 – Medical Devices – Applications of Risk Management, 2007 · ISO15223-1 – Medical Devices – Symbols to be used with Medical Device Labels, Labelling, and Information to be Supplied, 2007 6 J. Performance Characteristics: 1. Analytical Performance: Performance for the ARIES® System was established in the clearance of the assay, the ARIES® HSV1&2 Assay (k151906). a. Accuracy: See k151906 b. Precision/Reproducibility: See k151906 c. Linearity: See k151906 d. Carryover: See k151906 e. Interfering Substances: See k151906 2. Other Supportive Instrument Performance Data Not Covered Above: Not applicable K. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Predicate device name:

idK151917_s0_e2000

K151917.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY INSTRUMENT ONLY TEMPLATE A. 510(k) Number: k151917 B. Purpose for Submission: New instrument for use with the ARIES® HSV 1&2 Assay cleared under k151906 C. Manufacturer and Instrument Name: Luminex Corporation, ARIES® System D. Type of Test or Tests Performed: Nucleic-acid amplification testing E. System Descriptions: 1. Device Description: The ARIES® System is a clinical multiplex test system that automates and integrates extraction of nucleic acid from a clinical sample, performs real -time PCR, and measuring and sorting multiple signals generated in an in vitro diagnostic assay. The instrument system is used with specific IVD assays to measure multiple analytes. The device includes a signal reader unit, raw data storage mechanisms, data acquisition software and software to process detected signals. The ARIES® System is for in vitro diagnostic use by trained laboratory professionals in a controlled laboratory environment and is not intended for patient contact. The ARIES® System consists of the following; · a bench top instrument with two separate modules each with a magazine rack to accommodate six disposable single-use assay cassettes · methods for manipulating sample and reagent movement within the cassette · heaters for lysis, elution and nucleic acid amplification · 6 optical channels · fluorometer for real-time PCR fluorescence detection and melt analysis · methods for thermal and optical calibration · software for running and analyzing IVD assays 2. Principles of Operation: a. Device Features Controlled by Software: 2 The ARIES® SYSTEM instrument uses the ARIES® Software 1.0 software and the ARIES® Assay Protocol file for data acquisition, analysis, and reporting. The ARIES® instrument software is installed on the embedded PC and controls the two modules housed in the instrument. The ARIES® Instrument is a Real Time PCR Instrument. The ARIES® instrument software provides the interface between the ARIES® Software 1.0 and the ARIES® system hardware. The ARIES® system software communicates to the instrument software to manage operations of the system, including manipulation of sample and reagent movement within the cassette, control of heaters for lysis, elution and nucleic acid amplification, controlling the fluorimeter for real-time PCR bulk fluorescence detection and melt analysis, controlling thermal and optical calibration and data analysis for IVD assays run on the system. The ARIES® Software 1.0 software is installed in an embedded computer and provides the graphical user interface (GUI) application that is intended to be the end- user interface to the ARIES® instrument. The ARIES® Software 1.0 software is responsible for providing the environment in which an end-user runs and reports assays, administers, maintains, and sets default settings for the system. The ARIES® Assay Protocol Software is a framework that allows running assays and generating reports on an ARIES® instrument. The ARIES® Assay Protocol Software is contained within an assay protocol template. This template is a read-only type of assay protocol file that contains a specific script, data reduction, assay editor tool, and reports, and default assay parameters and blank call logic. The ARIES® Assay Protocol file that is generated contains assay logic (rules that specify clinical outcomes), data reduction runtime files (DLL), and assay configuration parameters (script parameters that control the instrument for running a sample in a cassette and data reduction algorithm parameters). b. Operational Environment (Off-the-Shelf Software): The ARIES® Software 1.0 software uses some commercial off-the-shelf software components. The sponsor provided detailed documentation for the OTS used, including validation, for both the ARIES® Software 1.0 software and the ARIES® Assay Protocol Software. For the ARIES® Assay Protocol Software used by Luminex, the recommended configuration for each computer is: • Windows 7 Professional SP1 (US English, 32 bit or 64 bit) • 2.8 GHz Intel Dual Core (or higher) • 4 Gb RAM (or higher) • 160 GB hard drive (or higher) The programming language used to develop the ARIES® Software 1.0 software was 3 Microsoft Visual C#. Instrument control software was written in a combination and C# and C++. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___x_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___x_____ 4. Specimen Identification: A barcode reader may be used for entry of sample IDs, or they may be entered manually. 5. Specimen Sampling and Handling: Samples are manually prepared according to assay manufacturer’s suggestions and are transferred to an assay specific cassette for analysis. 6. Calibration: Calibration is performed by Luminex service personnel using ARIES® System Verification Cassettes. 7. Quality Control: Each ARIES® assay cassette includes a Sample Process Control (SPC). The SPC has a known melting temperature (Tm) range and cycle threshold (Ct) range. Each time an assay is run, the system measures the temperature and fluorescence intensity of the SPC control to ensure the thermal and optical subsystems have remained in calibration. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes_____x___ or No________ 4 F. Regulatory Information: 1. Regulation section: 21 CFR 862.2570 Instrumentation for clinical multiplex test systems 2. Classification: Class II (special controls) 3 Product code: OOI – Real-time nucleic acid amplification 4. Panel: Chemistry (75) G. Intended Use: 1. Indication(s) for Use: The Luminex ARIES® System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: BD Diagnostics (Becton, Dickinson and Company), BD MAX System K111860 2. Comparison with Predicate Device: Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Intended Use The Luminex ARIES® System is an in vitro Same 5 Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence- based PCR. Sample Preparation Method Automated nucleic acid lysis and extraction by the ARIES® system Same Assay Format Amplification: Real Time PCR Detection: Fluorgenic Same Interpretation of Test Results Automated (Diagnostic software of Luminex ARIES® System) Same Differences Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Fluidics Self-contained Manual sample preparation Assay Cartridge · Cartridge is closed to the environment · Single Use · Reagent strips are open to the environment · Can be used twice Fluorescence Channels Six (6) channels Five (5) channels Software Software resides on the ARIES® System Software resides on an all- in-one computer I. Special Control/Guidance Document Referenced (if applicable): · IEC60825 – Safety of laser products, 2nd edition, 2007 · IEC62304, - Medical Device Software – Software Life Cycle Processes, 2006 · ISO 14971 – Medical Devices – Applications of Risk Management, 2007 · ISO15223-1 – Medical Devices – Symbols to be used with Medical Device Labels, Labelling, and Information to be Supplied, 2007 6 J. Performance Characteristics: 1. Analytical Performance: Performance for the ARIES® System was established in the clearance of the assay, the ARIES® HSV1&2 Assay (k151906). a. Accuracy: See k151906 b. Precision/Reproducibility: See k151906 c. Linearity: See k151906 d. Carryover: See k151906 e. Interfering Substances: See k151906 2. Other Supportive Instrument Performance Data Not Covered Above: Not applicable K. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK151917_s0_e2000

K151917.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY INSTRUMENT ONLY TEMPLATE A. 510(k) Number: k151917 B. Purpose for Submission: New instrument for use with the ARIES® HSV 1&2 Assay cleared under k151906 C. Manufacturer and Instrument Name: Luminex Corporation, ARIES® System D. Type of Test or Tests Performed: Nucleic-acid amplification testing E. System Descriptions: 1. Device Description: The ARIES® System is a clinical multiplex test system that automates and integrates extraction of nucleic acid from a clinical sample, performs real -time PCR, and measuring and sorting multiple signals generated in an in vitro diagnostic assay. The instrument system is used with specific IVD assays to measure multiple analytes. The device includes a signal reader unit, raw data storage mechanisms, data acquisition software and software to process detected signals. The ARIES® System is for in vitro diagnostic use by trained laboratory professionals in a controlled laboratory environment and is not intended for patient contact. The ARIES® System consists of the following; · a bench top instrument with two separate modules each with a magazine rack to accommodate six disposable single-use assay cassettes · methods for manipulating sample and reagent movement within the cassette · heaters for lysis, elution and nucleic acid amplification · 6 optical channels · fluorometer for real-time PCR fluorescence detection and melt analysis · methods for thermal and optical calibration · software for running and analyzing IVD assays 2. Principles of Operation: a. Device Features Controlled by Software: 2 The ARIES® SYSTEM instrument uses the ARIES® Software 1.0 software and the ARIES® Assay Protocol file for data acquisition, analysis, and reporting. The ARIES® instrument software is installed on the embedded PC and controls the two modules housed in the instrument. The ARIES® Instrument is a Real Time PCR Instrument. The ARIES® instrument software provides the interface between the ARIES® Software 1.0 and the ARIES® system hardware. The ARIES® system software communicates to the instrument software to manage operations of the system, including manipulation of sample and reagent movement within the cassette, control of heaters for lysis, elution and nucleic acid amplification, controlling the fluorimeter for real-time PCR bulk fluorescence detection and melt analysis, controlling thermal and optical calibration and data analysis for IVD assays run on the system. The ARIES® Software 1.0 software is installed in an embedded computer and provides the graphical user interface (GUI) application that is intended to be the end- user interface to the ARIES® instrument. The ARIES® Software 1.0 software is responsible for providing the environment in which an end-user runs and reports assays, administers, maintains, and sets default settings for the system. The ARIES® Assay Protocol Software is a framework that allows running assays and generating reports on an ARIES® instrument. The ARIES® Assay Protocol Software is contained within an assay protocol template. This template is a read-only type of assay protocol file that contains a specific script, data reduction, assay editor tool, and reports, and default assay parameters and blank call logic. The ARIES® Assay Protocol file that is generated contains assay logic (rules that specify clinical outcomes), data reduction runtime files (DLL), and assay configuration parameters (script parameters that control the instrument for running a sample in a cassette and data reduction algorithm parameters). b. Operational Environment (Off-the-Shelf Software): The ARIES® Software 1.0 software uses some commercial off-the-shelf software components. The sponsor provided detailed documentation for the OTS used, including validation, for both the ARIES® Software 1.0 software and the ARIES® Assay Protocol Software. For the ARIES® Assay Protocol Software used by Luminex, the recommended configuration for each computer is: • Windows 7 Professional SP1 (US English, 32 bit or 64 bit) • 2.8 GHz Intel Dual Core (or higher) • 4 Gb RAM (or higher) • 160 GB hard drive (or higher) The programming language used to develop the ARIES® Software 1.0 software was 3 Microsoft Visual C#. Instrument control software was written in a combination and C# and C++. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___x_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___x_____ 4. Specimen Identification: A barcode reader may be used for entry of sample IDs, or they may be entered manually. 5. Specimen Sampling and Handling: Samples are manually prepared according to assay manufacturer’s suggestions and are transferred to an assay specific cassette for analysis. 6. Calibration: Calibration is performed by Luminex service personnel using ARIES® System Verification Cassettes. 7. Quality Control: Each ARIES® assay cassette includes a Sample Process Control (SPC). The SPC has a known melting temperature (Tm) range and cycle threshold (Ct) range. Each time an assay is run, the system measures the temperature and fluorescence intensity of the SPC control to ensure the thermal and optical subsystems have remained in calibration. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes_____x___ or No________ 4 F. Regulatory Information: 1. Regulation section: 21 CFR 862.2570 Instrumentation for clinical multiplex test systems 2. Classification: Class II (special controls) 3 Product code: OOI – Real-time nucleic acid amplification 4. Panel: Chemistry (75) G. Intended Use: 1. Indication(s) for Use: The Luminex ARIES® System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: BD Diagnostics (Becton, Dickinson and Company), BD MAX System K111860 2. Comparison with Predicate Device: Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Intended Use The Luminex ARIES® System is an in vitro Same 5 Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence- based PCR. Sample Preparation Method Automated nucleic acid lysis and extraction by the ARIES® system Same Assay Format Amplification: Real Time PCR Detection: Fluorgenic Same Interpretation of Test Results Automated (Diagnostic software of Luminex ARIES® System) Same Differences Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Fluidics Self-contained Manual sample preparation Assay Cartridge · Cartridge is closed to the environment · Single Use · Reagent strips are open to the environment · Can be used twice Fluorescence Channels Six (6) channels Five (5) channels Software Software resides on the ARIES® System Software resides on an all- in-one computer I. Special Control/Guidance Document Referenced (if applicable): · IEC60825 – Safety of laser products, 2nd edition, 2007 · IEC62304, - Medical Device Software – Software Life Cycle Processes, 2006 · ISO 14971 – Medical Devices – Applications of Risk Management, 2007 · ISO15223-1 – Medical Devices – Symbols to be used with Medical Device Labels, Labelling, and Information to be Supplied, 2007 6 J. Performance Characteristics: 1. Analytical Performance: Performance for the ARIES® System was established in the clearance of the assay, the ARIES® HSV1&2 Assay (k151906). a. Accuracy: See k151906 b. Precision/Reproducibility: See k151906 c. Linearity: See k151906 d. Carryover: See k151906 e. Interfering Substances: See k151906 2. Other Supportive Instrument Performance Data Not Covered Above: Not applicable K. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK151917_s0_e2000

K151917.txt

applicant

Luminex Corporation

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY INSTRUMENT ONLY TEMPLATE A. 510(k) Number: k151917 B. Purpose for Submission: New instrument for use with the ARIES® HSV 1&2 Assay cleared under k151906 C. Manufacturer and Instrument Name: Luminex Corporation, ARIES® System D. Type of Test or Tests Performed: Nucleic-acid amplification testing E. System Descriptions: 1. Device Description: The ARIES® System is a clinical multiplex test system that automates and integrates extraction of nucleic acid from a clinical sample, performs real -time PCR, and measuring and sorting multiple signals generated in an in vitro diagnostic assay. The instrument system is used with specific IVD assays to measure multiple analytes. The device includes a signal reader unit, raw data storage mechanisms, data acquisition software and software to process detected signals. The ARIES® System is for in vitro diagnostic use by trained laboratory professionals in a controlled laboratory environment and is not intended for patient contact. The ARIES® System consists of the following; · a bench top instrument with two separate modules each with a magazine rack to accommodate six disposable single-use assay cassettes · methods for manipulating sample and reagent movement within the cassette · heaters for lysis, elution and nucleic acid amplification · 6 optical channels · fluorometer for real-time PCR fluorescence detection and melt analysis · methods for thermal and optical calibration · software for running and analyzing IVD assays 2. Principles of Operation: a. Device Features Controlled by Software: 2 The ARIES® SYSTEM instrument uses the ARIES® Software 1.0 software and the ARIES® Assay Protocol file for data acquisition, analysis, and reporting. The ARIES® instrument software is installed on the embedded PC and controls the two modules housed in the instrument. The ARIES® Instrument is a Real Time PCR Instrument. The ARIES® instrument software provides the interface between the ARIES® Software 1.0 and the ARIES® system hardware. The ARIES® system software communicates to the instrument software to manage operations of the system, including manipulation of sample and reagent movement within the cassette, control of heaters for lysis, elution and nucleic acid amplification, controlling the fluorimeter for real-time PCR bulk fluorescence detection and melt analysis, controlling thermal and optical calibration and data analysis for IVD assays run on the system. The ARIES® Software 1.0 software is installed in an embedded computer and provides the graphical user interface (GUI) application that is intended to be the end- user interface to the ARIES® instrument. The ARIES® Software 1.0 software is responsible for providing the environment in which an end-user runs and reports assays, administers, maintains, and sets default settings for the system. The ARIES® Assay Protocol Software is a framework that allows running assays and generating reports on an ARIES® instrument. The ARIES® Assay Protocol Software is contained within an assay protocol template. This template is a read-only type of assay protocol file that contains a specific script, data reduction, assay editor tool, and reports, and default assay parameters and blank call logic. The ARIES® Assay Protocol file that is generated contains assay logic (rules that specify clinical outcomes), data reduction runtime files (DLL), and assay configuration parameters (script parameters that control the instrument for running a sample in a cassette and data reduction algorithm parameters). b. Operational Environment (Off-the-Shelf Software): The ARIES® Software 1.0 software uses some commercial off-the-shelf software components. The sponsor provided detailed documentation for the OTS used, including validation, for both the ARIES® Software 1.0 software and the ARIES® Assay Protocol Software. For the ARIES® Assay Protocol Software used by Luminex, the recommended configuration for each computer is: • Windows 7 Professional SP1 (US English, 32 bit or 64 bit) • 2.8 GHz Intel Dual Core (or higher) • 4 Gb RAM (or higher) • 160 GB hard drive (or higher) The programming language used to develop the ARIES® Software 1.0 software was 3 Microsoft Visual C#. Instrument control software was written in a combination and C# and C++. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___x_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___x_____ 4. Specimen Identification: A barcode reader may be used for entry of sample IDs, or they may be entered manually. 5. Specimen Sampling and Handling: Samples are manually prepared according to assay manufacturer’s suggestions and are transferred to an assay specific cassette for analysis. 6. Calibration: Calibration is performed by Luminex service personnel using ARIES® System Verification Cassettes. 7. Quality Control: Each ARIES® assay cassette includes a Sample Process Control (SPC). The SPC has a known melting temperature (Tm) range and cycle threshold (Ct) range. Each time an assay is run, the system measures the temperature and fluorescence intensity of the SPC control to ensure the thermal and optical subsystems have remained in calibration. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes_____x___ or No________ 4 F. Regulatory Information: 1. Regulation section: 21 CFR 862.2570 Instrumentation for clinical multiplex test systems 2. Classification: Class II (special controls) 3 Product code: OOI – Real-time nucleic acid amplification 4. Panel: Chemistry (75) G. Intended Use: 1. Indication(s) for Use: The Luminex ARIES® System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: BD Diagnostics (Becton, Dickinson and Company), BD MAX System K111860 2. Comparison with Predicate Device: Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Intended Use The Luminex ARIES® System is an in vitro Same 5 Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence- based PCR. Sample Preparation Method Automated nucleic acid lysis and extraction by the ARIES® system Same Assay Format Amplification: Real Time PCR Detection: Fluorgenic Same Interpretation of Test Results Automated (Diagnostic software of Luminex ARIES® System) Same Differences Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Fluidics Self-contained Manual sample preparation Assay Cartridge · Cartridge is closed to the environment · Single Use · Reagent strips are open to the environment · Can be used twice Fluorescence Channels Six (6) channels Five (5) channels Software Software resides on the ARIES® System Software resides on an all- in-one computer I. Special Control/Guidance Document Referenced (if applicable): · IEC60825 – Safety of laser products, 2nd edition, 2007 · IEC62304, - Medical Device Software – Software Life Cycle Processes, 2006 · ISO 14971 – Medical Devices – Applications of Risk Management, 2007 · ISO15223-1 – Medical Devices – Symbols to be used with Medical Device Labels, Labelling, and Information to be Supplied, 2007 6 J. Performance Characteristics: 1. Analytical Performance: Performance for the ARIES® System was established in the clearance of the assay, the ARIES® HSV1&2 Assay (k151906). a. Accuracy: See k151906 b. Precision/Reproducibility: See k151906 c. Linearity: See k151906 d. Carryover: See k151906 e. Interfering Substances: See k151906 2. Other Supportive Instrument Performance Data Not Covered Above: Not applicable K. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Applicant:

idK151917_s0_e2000

K151917.txt

regulation section

21 CFR 862.2570 Instrumentation for clinical multiplex test systems

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY INSTRUMENT ONLY TEMPLATE A. 510(k) Number: k151917 B. Purpose for Submission: New instrument for use with the ARIES® HSV 1&2 Assay cleared under k151906 C. Manufacturer and Instrument Name: Luminex Corporation, ARIES® System D. Type of Test or Tests Performed: Nucleic-acid amplification testing E. System Descriptions: 1. Device Description: The ARIES® System is a clinical multiplex test system that automates and integrates extraction of nucleic acid from a clinical sample, performs real -time PCR, and measuring and sorting multiple signals generated in an in vitro diagnostic assay. The instrument system is used with specific IVD assays to measure multiple analytes. The device includes a signal reader unit, raw data storage mechanisms, data acquisition software and software to process detected signals. The ARIES® System is for in vitro diagnostic use by trained laboratory professionals in a controlled laboratory environment and is not intended for patient contact. The ARIES® System consists of the following; · a bench top instrument with two separate modules each with a magazine rack to accommodate six disposable single-use assay cassettes · methods for manipulating sample and reagent movement within the cassette · heaters for lysis, elution and nucleic acid amplification · 6 optical channels · fluorometer for real-time PCR fluorescence detection and melt analysis · methods for thermal and optical calibration · software for running and analyzing IVD assays 2. Principles of Operation: a. Device Features Controlled by Software: 2 The ARIES® SYSTEM instrument uses the ARIES® Software 1.0 software and the ARIES® Assay Protocol file for data acquisition, analysis, and reporting. The ARIES® instrument software is installed on the embedded PC and controls the two modules housed in the instrument. The ARIES® Instrument is a Real Time PCR Instrument. The ARIES® instrument software provides the interface between the ARIES® Software 1.0 and the ARIES® system hardware. The ARIES® system software communicates to the instrument software to manage operations of the system, including manipulation of sample and reagent movement within the cassette, control of heaters for lysis, elution and nucleic acid amplification, controlling the fluorimeter for real-time PCR bulk fluorescence detection and melt analysis, controlling thermal and optical calibration and data analysis for IVD assays run on the system. The ARIES® Software 1.0 software is installed in an embedded computer and provides the graphical user interface (GUI) application that is intended to be the end- user interface to the ARIES® instrument. The ARIES® Software 1.0 software is responsible for providing the environment in which an end-user runs and reports assays, administers, maintains, and sets default settings for the system. The ARIES® Assay Protocol Software is a framework that allows running assays and generating reports on an ARIES® instrument. The ARIES® Assay Protocol Software is contained within an assay protocol template. This template is a read-only type of assay protocol file that contains a specific script, data reduction, assay editor tool, and reports, and default assay parameters and blank call logic. The ARIES® Assay Protocol file that is generated contains assay logic (rules that specify clinical outcomes), data reduction runtime files (DLL), and assay configuration parameters (script parameters that control the instrument for running a sample in a cassette and data reduction algorithm parameters). b. Operational Environment (Off-the-Shelf Software): The ARIES® Software 1.0 software uses some commercial off-the-shelf software components. The sponsor provided detailed documentation for the OTS used, including validation, for both the ARIES® Software 1.0 software and the ARIES® Assay Protocol Software. For the ARIES® Assay Protocol Software used by Luminex, the recommended configuration for each computer is: • Windows 7 Professional SP1 (US English, 32 bit or 64 bit) • 2.8 GHz Intel Dual Core (or higher) • 4 Gb RAM (or higher) • 160 GB hard drive (or higher) The programming language used to develop the ARIES® Software 1.0 software was 3 Microsoft Visual C#. Instrument control software was written in a combination and C# and C++. 3. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___x_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ___x_____ 4. Specimen Identification: A barcode reader may be used for entry of sample IDs, or they may be entered manually. 5. Specimen Sampling and Handling: Samples are manually prepared according to assay manufacturer’s suggestions and are transferred to an assay specific cassette for analysis. 6. Calibration: Calibration is performed by Luminex service personnel using ARIES® System Verification Cassettes. 7. Quality Control: Each ARIES® assay cassette includes a Sample Process Control (SPC). The SPC has a known melting temperature (Tm) range and cycle threshold (Ct) range. Each time an assay is run, the system measures the temperature and fluorescence intensity of the SPC control to ensure the thermal and optical subsystems have remained in calibration. 8. Software: FDA has reviewed applicant’s Hazard Analysis and Software Development processes for this line of product types: Yes_____x___ or No________ 4 F. Regulatory Information: 1. Regulation section: 21 CFR 862.2570 Instrumentation for clinical multiplex test systems 2. Classification: Class II (special controls) 3 Product code: OOI – Real-time nucleic acid amplification 4. Panel: Chemistry (75) G. Intended Use: 1. Indication(s) for Use: The Luminex ARIES® System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR. 2. Special Conditions for Use Statement(s): For prescription use only. H. Substantial Equivalence Information: 1. Predicate Device Name(s) and 510(k) numbers: BD Diagnostics (Becton, Dickinson and Company), BD MAX System K111860 2. Comparison with Predicate Device: Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Intended Use The Luminex ARIES® System is an in vitro Same 5 Similarities Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence- based PCR. Sample Preparation Method Automated nucleic acid lysis and extraction by the ARIES® system Same Assay Format Amplification: Real Time PCR Detection: Fluorgenic Same Interpretation of Test Results Automated (Diagnostic software of Luminex ARIES® System) Same Differences Item New Device: Luminex ARIES® System Predicate Device: BD Max System (k111860) Fluidics Self-contained Manual sample preparation Assay Cartridge · Cartridge is closed to the environment · Single Use · Reagent strips are open to the environment · Can be used twice Fluorescence Channels Six (6) channels Five (5) channels Software Software resides on the ARIES® System Software resides on an all- in-one computer I. Special Control/Guidance Document Referenced (if applicable): · IEC60825 – Safety of laser products, 2nd edition, 2007 · IEC62304, - Medical Device Software – Software Life Cycle Processes, 2006 · ISO 14971 – Medical Devices – Applications of Risk Management, 2007 · ISO15223-1 – Medical Devices – Symbols to be used with Medical Device Labels, Labelling, and Information to be Supplied, 2007 6 J. Performance Characteristics: 1. Analytical Performance: Performance for the ARIES® System was established in the clearance of the assay, the ARIES® HSV1&2 Assay (k151906). a. Accuracy: See k151906 b. Precision/Reproducibility: See k151906 c. Linearity: See k151906 d. Carryover: See k151906 e. Interfering Substances: See k151906 2. Other Supportive Instrument Performance Data Not Covered Above: Not applicable K. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. L. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Regulation section:

idK193393_s0_e2000

K193393.txt

purpose for submission

Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL)

New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY I. Background Information: A. 510(k) Number K193393 B. Applicant Leica Biosystems Newcastle Ltd. C. Proprietary and Established Names BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) D. Regulatory Information Product Code(s) Classification Regulation Section Panel MXZ Class II 21 CFR 864.1860 - Immunohistochemistry Reagents and Kits II. Submission/Device Overview: A. Purpose for Submission: Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL) B. Measurand: K193393 - Page 2 of 14 Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue. C. Type of Test: Immunohistochemistry (IHC) III. Intended Use/Indications for Use: A. Intended Use(s): See Indications for Use below. B. Indication(s) for Use: Ready-to-Use Format For in vitro diagnostic use. BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX or BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterne Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit. Concentrated Liquid Antibody Format For in vitro diagnostic use. Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be K193393 - Page 3 of 14 complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. C. Special Conditions for Use Statement(s): Rx - For Prescription Use Only D. Special Instrument Requirements: BOND-MAX and BOND-III staining platforms. IV. Device/System Characteristics: A. Device Description: BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) • Progesterone Receptor Clone (16) or PR (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and supplied in Tris buffered saline with carrier protein containing 0.35% ProClin 950 as preservative. This antibody is utilized to perform a qualitative IHC assay to identify Progesterone Receptor (PR) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination. There are two configurations of the RTU antibody: 7 mL and 30 mL. • PR (16) Primary Antibody is provided in a Ready-to- Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection kit. The concentrated liquid format is for manual staining protocols. • The concentrated liquid antibody format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA. BOND-III Instrument • The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, IHC staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND K193393 - Page 4 of 14 application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP). B. Principle of Operation: Immunohistochemical techniques are used to demonstrate the presence of antigens in tissue and cells. The recommended staining protocol for PR (16) primary antibody is IHC Protocol F: Heat induced epitope retrieval is recommended using Bond Epitope Retrieval Solution 2 for 20 minutes. Bond Polymer Refine Detection utilizes a novel controlled polymerization technology to prepare polymeric HRP-linker antibody conjugates. Bond Polymer Refine Detection works as follows: • The specimen is incubated with hydrogen peroxide to quench endogenous peroxidase activity. • Bond RTU Primary Antibody PR (16) is applied. • A post primary antibody solution enhances penetration of the subsequent polymer reagent • A poly-HRP anti-mouse/rabbit IgG reagent localizes the primary antibody. • The substrate chromogen, 3,3’- diaminobenzidine (DAB), visualizes the complex via a brown precipitate. • Hematoxylin (blue) counterstaining allows the visualization of cell nuclei using Bond Polymer Refine Detection in combination with the automated BOND-MAX system reduces the possibility of human error and inherent variability resulting from individual reagent dilution, manual pipetting and reagent application. Table 1: PR IHC Staining Protocol F on BOND-III and BOND-MAX Instruments BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) IHC Protocol F 1 Peroxide Block Ambient 05:00 2 BOND Wash Solution Ambient 00:00 3 BOND Wash Solution Ambient 00:00 4 BOND Wash Solution Ambient 00:00 5 PRIMARY Antibody (PGR) Ambient 15:00 6 BOND Wash Solution Ambient 00:00 7 BOND Wash Solution Ambient 00:00 8 BOND Wash Solution Ambient 00:00 9 Post Primary Ambient 08:00 10 BOND Wash Solution Ambient 02:00 11 BOND Wash Solution Ambient 02:00 12 BOND Wash Solution Ambient 02:00 13 Polymer Detection Ambient 08:00 14 BOND Wash Solution Ambient 02:00 15 BOND Wash Solution Ambient 02:00 K193393 - Page 5 of 14 BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) 16 Deionized Water Ambient 00:00 17 Mixed DAB Refine Ambient 00:00 18 Mixed DAB Refine Ambient 10:00 19 Deionized Water Ambient 00:00 20 Deionized Water Ambient 00:00 Purpose for submission:

idK193393_s0_e2000

K193393.txt

measurand

Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue.

New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY I. Background Information: A. 510(k) Number K193393 B. Applicant Leica Biosystems Newcastle Ltd. C. Proprietary and Established Names BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) D. Regulatory Information Product Code(s) Classification Regulation Section Panel MXZ Class II 21 CFR 864.1860 - Immunohistochemistry Reagents and Kits II. Submission/Device Overview: A. Purpose for Submission: Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL) B. Measurand: K193393 - Page 2 of 14 Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue. C. Type of Test: Immunohistochemistry (IHC) III. Intended Use/Indications for Use: A. Intended Use(s): See Indications for Use below. B. Indication(s) for Use: Ready-to-Use Format For in vitro diagnostic use. BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX or BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterne Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit. Concentrated Liquid Antibody Format For in vitro diagnostic use. Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be K193393 - Page 3 of 14 complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. C. Special Conditions for Use Statement(s): Rx - For Prescription Use Only D. Special Instrument Requirements: BOND-MAX and BOND-III staining platforms. IV. Device/System Characteristics: A. Device Description: BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) • Progesterone Receptor Clone (16) or PR (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and supplied in Tris buffered saline with carrier protein containing 0.35% ProClin 950 as preservative. This antibody is utilized to perform a qualitative IHC assay to identify Progesterone Receptor (PR) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination. There are two configurations of the RTU antibody: 7 mL and 30 mL. • PR (16) Primary Antibody is provided in a Ready-to- Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection kit. The concentrated liquid format is for manual staining protocols. • The concentrated liquid antibody format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA. BOND-III Instrument • The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, IHC staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND K193393 - Page 4 of 14 application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP). B. Principle of Operation: Immunohistochemical techniques are used to demonstrate the presence of antigens in tissue and cells. The recommended staining protocol for PR (16) primary antibody is IHC Protocol F: Heat induced epitope retrieval is recommended using Bond Epitope Retrieval Solution 2 for 20 minutes. Bond Polymer Refine Detection utilizes a novel controlled polymerization technology to prepare polymeric HRP-linker antibody conjugates. Bond Polymer Refine Detection works as follows: • The specimen is incubated with hydrogen peroxide to quench endogenous peroxidase activity. • Bond RTU Primary Antibody PR (16) is applied. • A post primary antibody solution enhances penetration of the subsequent polymer reagent • A poly-HRP anti-mouse/rabbit IgG reagent localizes the primary antibody. • The substrate chromogen, 3,3’- diaminobenzidine (DAB), visualizes the complex via a brown precipitate. • Hematoxylin (blue) counterstaining allows the visualization of cell nuclei using Bond Polymer Refine Detection in combination with the automated BOND-MAX system reduces the possibility of human error and inherent variability resulting from individual reagent dilution, manual pipetting and reagent application. Table 1: PR IHC Staining Protocol F on BOND-III and BOND-MAX Instruments BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) IHC Protocol F 1 Peroxide Block Ambient 05:00 2 BOND Wash Solution Ambient 00:00 3 BOND Wash Solution Ambient 00:00 4 BOND Wash Solution Ambient 00:00 5 PRIMARY Antibody (PGR) Ambient 15:00 6 BOND Wash Solution Ambient 00:00 7 BOND Wash Solution Ambient 00:00 8 BOND Wash Solution Ambient 00:00 9 Post Primary Ambient 08:00 10 BOND Wash Solution Ambient 02:00 11 BOND Wash Solution Ambient 02:00 12 BOND Wash Solution Ambient 02:00 13 Polymer Detection Ambient 08:00 14 BOND Wash Solution Ambient 02:00 15 BOND Wash Solution Ambient 02:00 K193393 - Page 5 of 14 BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) 16 Deionized Water Ambient 00:00 17 Mixed DAB Refine Ambient 00:00 18 Mixed DAB Refine Ambient 10:00 19 Deionized Water Ambient 00:00 20 Deionized Water Ambient 00:00 Measurand:

idK193393_s0_e2000

K193393.txt

type of test

Immunohistochemistry (IHC)

03 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY I. Background Information: A. 510(k) Number K193393 B. Applicant Leica Biosystems Newcastle Ltd. C. Proprietary and Established Names BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) D. Regulatory Information Product Code(s) Classification Regulation Section Panel MXZ Class II 21 CFR 864.1860 - Immunohistochemistry Reagents and Kits II. Submission/Device Overview: A. Purpose for Submission: Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL) B. Measurand: K193393 - Page 2 of 14 Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue. C. Type of Test: Immunohistochemistry (IHC) III. Intended Use/Indications for Use: A. Intended Use(s): See Indications for Use below. B. Indication(s) for Use: Ready-to-Use Format For in vitro diagnostic use. BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX or BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterne Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit. Concentrated Liquid Antibody Format For in vitro diagnostic use. Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be K193393 - Page 3 of 14 complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. C. Special Conditions for Use Statement(s): Rx - For Prescription Use Only D. Special Instrument Requirements: BOND-MAX and BOND-III staining platforms. IV. Device/System Characteristics: A. Device Description: BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) • Progesterone Receptor Clone (16) or PR (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and supplied in Tris buffered saline with carrier protein containing 0.35% ProClin 950 as preservative. This antibody is utilized to perform a qualitative IHC assay to identify Progesterone Receptor (PR) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination. There are two configurations of the RTU antibody: 7 mL and 30 mL. • PR (16) Primary Antibody is provided in a Ready-to- Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection kit. The concentrated liquid format is for manual staining protocols. • The concentrated liquid antibody format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA. BOND-III Instrument • The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, IHC staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND K193393 - Page 4 of 14 application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP). B. Principle of Operation: Immunohistochemical techniques are used to demonstrate the presence of antigens in tissue and cells. The recommended staining protocol for PR (16) primary antibody is IHC Protocol F: Heat induced epitope retrieval is recommended using Bond Epitope Retrieval Solution 2 for 20 minutes. Bond Polymer Refine Detection utilizes a novel controlled polymerization technology to prepare polymeric HRP-linker antibody conjugates. Bond Polymer Refine Detection works as follows: • The specimen is incubated with hydrogen peroxide to quench endogenous peroxidase activity. • Bond RTU Primary Antibody PR (16) is applied. • A post primary antibody solution enhances penetration of the subsequent polymer reagent • A poly-HRP anti-mouse/rabbit IgG reagent localizes the primary antibody. • The substrate chromogen, 3,3’- diaminobenzidine (DAB), visualizes the complex via a brown precipitate. • Hematoxylin (blue) counterstaining allows the visualization of cell nuclei using Bond Polymer Refine Detection in combination with the automated BOND-MAX system reduces the possibility of human error and inherent variability resulting from individual reagent dilution, manual pipetting and reagent application. Table 1: PR IHC Staining Protocol F on BOND-III and BOND-MAX Instruments BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) IHC Protocol F 1 Peroxide Block Ambient 05:00 2 BOND Wash Solution Ambient 00:00 3 BOND Wash Solution Ambient 00:00 4 BOND Wash Solution Ambient 00:00 5 PRIMARY Antibody (PGR) Ambient 15:00 6 BOND Wash Solution Ambient 00:00 7 BOND Wash Solution Ambient 00:00 8 BOND Wash Solution Ambient 00:00 9 Post Primary Ambient 08:00 10 BOND Wash Solution Ambient 02:00 11 BOND Wash Solution Ambient 02:00 12 BOND Wash Solution Ambient 02:00 13 Polymer Detection Ambient 08:00 14 BOND Wash Solution Ambient 02:00 15 BOND Wash Solution Ambient 02:00 K193393 - Page 5 of 14 BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) 16 Deionized Water Ambient 00:00 17 Mixed DAB Refine Ambient 00:00 18 Mixed DAB Refine Ambient 10:00 19 Deionized Water Ambient 00:00 20 Deionized Water Ambient 00:00 Type of test:

idK193393_s0_e2000

K193393.txt

classification

Class II

10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY I. Background Information: A. 510(k) Number K193393 B. Applicant Leica Biosystems Newcastle Ltd. C. Proprietary and Established Names BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) D. Regulatory Information Product Code(s) Classification Regulation Section Panel MXZ Class II 21 CFR 864.1860 - Immunohistochemistry Reagents and Kits II. Submission/Device Overview: A. Purpose for Submission: Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL) B. Measurand: K193393 - Page 2 of 14 Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue. C. Type of Test: Immunohistochemistry (IHC) III. Intended Use/Indications for Use: A. Intended Use(s): See Indications for Use below. B. Indication(s) for Use: Ready-to-Use Format For in vitro diagnostic use. BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX or BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterne Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit. Concentrated Liquid Antibody Format For in vitro diagnostic use. Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be K193393 - Page 3 of 14 complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. C. Special Conditions for Use Statement(s): Rx - For Prescription Use Only D. Special Instrument Requirements: BOND-MAX and BOND-III staining platforms. IV. Device/System Characteristics: A. Device Description: BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) • Progesterone Receptor Clone (16) or PR (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and supplied in Tris buffered saline with carrier protein containing 0.35% ProClin 950 as preservative. This antibody is utilized to perform a qualitative IHC assay to identify Progesterone Receptor (PR) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination. There are two configurations of the RTU antibody: 7 mL and 30 mL. • PR (16) Primary Antibody is provided in a Ready-to- Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection kit. The concentrated liquid format is for manual staining protocols. • The concentrated liquid antibody format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA. BOND-III Instrument • The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, IHC staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND K193393 - Page 4 of 14 application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP). B. Principle of Operation: Immunohistochemical techniques are used to demonstrate the presence of antigens in tissue and cells. The recommended staining protocol for PR (16) primary antibody is IHC Protocol F: Heat induced epitope retrieval is recommended using Bond Epitope Retrieval Solution 2 for 20 minutes. Bond Polymer Refine Detection utilizes a novel controlled polymerization technology to prepare polymeric HRP-linker antibody conjugates. Bond Polymer Refine Detection works as follows: • The specimen is incubated with hydrogen peroxide to quench endogenous peroxidase activity. • Bond RTU Primary Antibody PR (16) is applied. • A post primary antibody solution enhances penetration of the subsequent polymer reagent • A poly-HRP anti-mouse/rabbit IgG reagent localizes the primary antibody. • The substrate chromogen, 3,3’- diaminobenzidine (DAB), visualizes the complex via a brown precipitate. • Hematoxylin (blue) counterstaining allows the visualization of cell nuclei using Bond Polymer Refine Detection in combination with the automated BOND-MAX system reduces the possibility of human error and inherent variability resulting from individual reagent dilution, manual pipetting and reagent application. Table 1: PR IHC Staining Protocol F on BOND-III and BOND-MAX Instruments BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) IHC Protocol F 1 Peroxide Block Ambient 05:00 2 BOND Wash Solution Ambient 00:00 3 BOND Wash Solution Ambient 00:00 4 BOND Wash Solution Ambient 00:00 5 PRIMARY Antibody (PGR) Ambient 15:00 6 BOND Wash Solution Ambient 00:00 7 BOND Wash Solution Ambient 00:00 8 BOND Wash Solution Ambient 00:00 9 Post Primary Ambient 08:00 10 BOND Wash Solution Ambient 02:00 11 BOND Wash Solution Ambient 02:00 12 BOND Wash Solution Ambient 02:00 13 Polymer Detection Ambient 08:00 14 BOND Wash Solution Ambient 02:00 15 BOND Wash Solution Ambient 02:00 K193393 - Page 5 of 14 BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) 16 Deionized Water Ambient 00:00 17 Mixed DAB Refine Ambient 00:00 18 Mixed DAB Refine Ambient 10:00 19 Deionized Water Ambient 00:00 20 Deionized Water Ambient 00:00 Classification:

idK193393_s0_e2000

K193393.txt

product code

MXZ

10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY I. Background Information: A. 510(k) Number K193393 B. Applicant Leica Biosystems Newcastle Ltd. C. Proprietary and Established Names BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) D. Regulatory Information Product Code(s) Classification Regulation Section Panel MXZ Class II 21 CFR 864.1860 - Immunohistochemistry Reagents and Kits II. Submission/Device Overview: A. Purpose for Submission: Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL) B. Measurand: K193393 - Page 2 of 14 Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue. C. Type of Test: Immunohistochemistry (IHC) III. Intended Use/Indications for Use: A. Intended Use(s): See Indications for Use below. B. Indication(s) for Use: Ready-to-Use Format For in vitro diagnostic use. BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX or BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterne Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit. Concentrated Liquid Antibody Format For in vitro diagnostic use. Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be K193393 - Page 3 of 14 complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. C. Special Conditions for Use Statement(s): Rx - For Prescription Use Only D. Special Instrument Requirements: BOND-MAX and BOND-III staining platforms. IV. Device/System Characteristics: A. Device Description: BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) • Progesterone Receptor Clone (16) or PR (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and supplied in Tris buffered saline with carrier protein containing 0.35% ProClin 950 as preservative. This antibody is utilized to perform a qualitative IHC assay to identify Progesterone Receptor (PR) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination. There are two configurations of the RTU antibody: 7 mL and 30 mL. • PR (16) Primary Antibody is provided in a Ready-to- Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection kit. The concentrated liquid format is for manual staining protocols. • The concentrated liquid antibody format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA. BOND-III Instrument • The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, IHC staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND K193393 - Page 4 of 14 application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP). B. Principle of Operation: Immunohistochemical techniques are used to demonstrate the presence of antigens in tissue and cells. The recommended staining protocol for PR (16) primary antibody is IHC Protocol F: Heat induced epitope retrieval is recommended using Bond Epitope Retrieval Solution 2 for 20 minutes. Bond Polymer Refine Detection utilizes a novel controlled polymerization technology to prepare polymeric HRP-linker antibody conjugates. Bond Polymer Refine Detection works as follows: • The specimen is incubated with hydrogen peroxide to quench endogenous peroxidase activity. • Bond RTU Primary Antibody PR (16) is applied. • A post primary antibody solution enhances penetration of the subsequent polymer reagent • A poly-HRP anti-mouse/rabbit IgG reagent localizes the primary antibody. • The substrate chromogen, 3,3’- diaminobenzidine (DAB), visualizes the complex via a brown precipitate. • Hematoxylin (blue) counterstaining allows the visualization of cell nuclei using Bond Polymer Refine Detection in combination with the automated BOND-MAX system reduces the possibility of human error and inherent variability resulting from individual reagent dilution, manual pipetting and reagent application. Table 1: PR IHC Staining Protocol F on BOND-III and BOND-MAX Instruments BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) IHC Protocol F 1 Peroxide Block Ambient 05:00 2 BOND Wash Solution Ambient 00:00 3 BOND Wash Solution Ambient 00:00 4 BOND Wash Solution Ambient 00:00 5 PRIMARY Antibody (PGR) Ambient 15:00 6 BOND Wash Solution Ambient 00:00 7 BOND Wash Solution Ambient 00:00 8 BOND Wash Solution Ambient 00:00 9 Post Primary Ambient 08:00 10 BOND Wash Solution Ambient 02:00 11 BOND Wash Solution Ambient 02:00 12 BOND Wash Solution Ambient 02:00 13 Polymer Detection Ambient 08:00 14 BOND Wash Solution Ambient 02:00 15 BOND Wash Solution Ambient 02:00 K193393 - Page 5 of 14 BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) 16 Deionized Water Ambient 00:00 17 Mixed DAB Refine Ambient 00:00 18 Mixed DAB Refine Ambient 10:00 19 Deionized Water Ambient 00:00 20 Deionized Water Ambient 00:00 Product code:

idK193393_s0_e2000

K193393.txt

panel

Immunohistochemistry (IHC)

Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY I. Background Information: A. 510(k) Number K193393 B. Applicant Leica Biosystems Newcastle Ltd. C. Proprietary and Established Names BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) D. Regulatory Information Product Code(s) Classification Regulation Section Panel MXZ Class II 21 CFR 864.1860 - Immunohistochemistry Reagents and Kits II. Submission/Device Overview: A. Purpose for Submission: Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL) B. Measurand: K193393 - Page 2 of 14 Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue. C. Type of Test: Immunohistochemistry (IHC) III. Intended Use/Indications for Use: A. Intended Use(s): See Indications for Use below. B. Indication(s) for Use: Ready-to-Use Format For in vitro diagnostic use. BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX or BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterne Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit. Concentrated Liquid Antibody Format For in vitro diagnostic use. Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be K193393 - Page 3 of 14 complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. C. Special Conditions for Use Statement(s): Rx - For Prescription Use Only D. Special Instrument Requirements: BOND-MAX and BOND-III staining platforms. IV. Device/System Characteristics: A. Device Description: BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) • Progesterone Receptor Clone (16) or PR (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and supplied in Tris buffered saline with carrier protein containing 0.35% ProClin 950 as preservative. This antibody is utilized to perform a qualitative IHC assay to identify Progesterone Receptor (PR) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination. There are two configurations of the RTU antibody: 7 mL and 30 mL. • PR (16) Primary Antibody is provided in a Ready-to- Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection kit. The concentrated liquid format is for manual staining protocols. • The concentrated liquid antibody format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA. BOND-III Instrument • The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, IHC staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND K193393 - Page 4 of 14 application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP). B. Principle of Operation: Immunohistochemical techniques are used to demonstrate the presence of antigens in tissue and cells. The recommended staining protocol for PR (16) primary antibody is IHC Protocol F: Heat induced epitope retrieval is recommended using Bond Epitope Retrieval Solution 2 for 20 minutes. Bond Polymer Refine Detection utilizes a novel controlled polymerization technology to prepare polymeric HRP-linker antibody conjugates. Bond Polymer Refine Detection works as follows: • The specimen is incubated with hydrogen peroxide to quench endogenous peroxidase activity. • Bond RTU Primary Antibody PR (16) is applied. • A post primary antibody solution enhances penetration of the subsequent polymer reagent • A poly-HRP anti-mouse/rabbit IgG reagent localizes the primary antibody. • The substrate chromogen, 3,3’- diaminobenzidine (DAB), visualizes the complex via a brown precipitate. • Hematoxylin (blue) counterstaining allows the visualization of cell nuclei using Bond Polymer Refine Detection in combination with the automated BOND-MAX system reduces the possibility of human error and inherent variability resulting from individual reagent dilution, manual pipetting and reagent application. Table 1: PR IHC Staining Protocol F on BOND-III and BOND-MAX Instruments BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) IHC Protocol F 1 Peroxide Block Ambient 05:00 2 BOND Wash Solution Ambient 00:00 3 BOND Wash Solution Ambient 00:00 4 BOND Wash Solution Ambient 00:00 5 PRIMARY Antibody (PGR) Ambient 15:00 6 BOND Wash Solution Ambient 00:00 7 BOND Wash Solution Ambient 00:00 8 BOND Wash Solution Ambient 00:00 9 Post Primary Ambient 08:00 10 BOND Wash Solution Ambient 02:00 11 BOND Wash Solution Ambient 02:00 12 BOND Wash Solution Ambient 02:00 13 Polymer Detection Ambient 08:00 14 BOND Wash Solution Ambient 02:00 15 BOND Wash Solution Ambient 02:00 K193393 - Page 5 of 14 BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) 16 Deionized Water Ambient 00:00 17 Mixed DAB Refine Ambient 00:00 18 Mixed DAB Refine Ambient 10:00 19 Deionized Water Ambient 00:00 20 Deionized Water Ambient 00:00 Panel:

idK193393_s0_e2000

K193393.txt

intended use

See Indications for Use below.

03 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY I. Background Information: A. 510(k) Number K193393 B. Applicant Leica Biosystems Newcastle Ltd. C. Proprietary and Established Names BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) D. Regulatory Information Product Code(s) Classification Regulation Section Panel MXZ Class II 21 CFR 864.1860 - Immunohistochemistry Reagents and Kits II. Submission/Device Overview: A. Purpose for Submission: Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL) B. Measurand: K193393 - Page 2 of 14 Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue. C. Type of Test: Immunohistochemistry (IHC) III. Intended Use/Indications for Use: A. Intended Use(s): See Indications for Use below. B. Indication(s) for Use: Ready-to-Use Format For in vitro diagnostic use. BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX or BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterne Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit. Concentrated Liquid Antibody Format For in vitro diagnostic use. Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be K193393 - Page 3 of 14 complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. C. Special Conditions for Use Statement(s): Rx - For Prescription Use Only D. Special Instrument Requirements: BOND-MAX and BOND-III staining platforms. IV. Device/System Characteristics: A. Device Description: BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) • Progesterone Receptor Clone (16) or PR (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and supplied in Tris buffered saline with carrier protein containing 0.35% ProClin 950 as preservative. This antibody is utilized to perform a qualitative IHC assay to identify Progesterone Receptor (PR) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination. There are two configurations of the RTU antibody: 7 mL and 30 mL. • PR (16) Primary Antibody is provided in a Ready-to- Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection kit. The concentrated liquid format is for manual staining protocols. • The concentrated liquid antibody format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA. BOND-III Instrument • The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, IHC staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND K193393 - Page 4 of 14 application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP). B. Principle of Operation: Immunohistochemical techniques are used to demonstrate the presence of antigens in tissue and cells. The recommended staining protocol for PR (16) primary antibody is IHC Protocol F: Heat induced epitope retrieval is recommended using Bond Epitope Retrieval Solution 2 for 20 minutes. Bond Polymer Refine Detection utilizes a novel controlled polymerization technology to prepare polymeric HRP-linker antibody conjugates. Bond Polymer Refine Detection works as follows: • The specimen is incubated with hydrogen peroxide to quench endogenous peroxidase activity. • Bond RTU Primary Antibody PR (16) is applied. • A post primary antibody solution enhances penetration of the subsequent polymer reagent • A poly-HRP anti-mouse/rabbit IgG reagent localizes the primary antibody. • The substrate chromogen, 3,3’- diaminobenzidine (DAB), visualizes the complex via a brown precipitate. • Hematoxylin (blue) counterstaining allows the visualization of cell nuclei using Bond Polymer Refine Detection in combination with the automated BOND-MAX system reduces the possibility of human error and inherent variability resulting from individual reagent dilution, manual pipetting and reagent application. Table 1: PR IHC Staining Protocol F on BOND-III and BOND-MAX Instruments BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) IHC Protocol F 1 Peroxide Block Ambient 05:00 2 BOND Wash Solution Ambient 00:00 3 BOND Wash Solution Ambient 00:00 4 BOND Wash Solution Ambient 00:00 5 PRIMARY Antibody (PGR) Ambient 15:00 6 BOND Wash Solution Ambient 00:00 7 BOND Wash Solution Ambient 00:00 8 BOND Wash Solution Ambient 00:00 9 Post Primary Ambient 08:00 10 BOND Wash Solution Ambient 02:00 11 BOND Wash Solution Ambient 02:00 12 BOND Wash Solution Ambient 02:00 13 Polymer Detection Ambient 08:00 14 BOND Wash Solution Ambient 02:00 15 BOND Wash Solution Ambient 02:00 K193393 - Page 5 of 14 BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) 16 Deionized Water Ambient 00:00 17 Mixed DAB Refine Ambient 00:00 18 Mixed DAB Refine Ambient 10:00 19 Deionized Water Ambient 00:00 20 Deionized Water Ambient 00:00 Intended use:

idK193393_s0_e2000

K193393.txt

applicant

Leica Biosystems Newcastle Ltd.

10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY I. Background Information: A. 510(k) Number K193393 B. Applicant Leica Biosystems Newcastle Ltd. C. Proprietary and Established Names BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) D. Regulatory Information Product Code(s) Classification Regulation Section Panel MXZ Class II 21 CFR 864.1860 - Immunohistochemistry Reagents and Kits II. Submission/Device Overview: A. Purpose for Submission: Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL) B. Measurand: K193393 - Page 2 of 14 Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue. C. Type of Test: Immunohistochemistry (IHC) III. Intended Use/Indications for Use: A. Intended Use(s): See Indications for Use below. B. Indication(s) for Use: Ready-to-Use Format For in vitro diagnostic use. BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX or BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterne Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit. Concentrated Liquid Antibody Format For in vitro diagnostic use. Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be K193393 - Page 3 of 14 complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. C. Special Conditions for Use Statement(s): Rx - For Prescription Use Only D. Special Instrument Requirements: BOND-MAX and BOND-III staining platforms. IV. Device/System Characteristics: A. Device Description: BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) • Progesterone Receptor Clone (16) or PR (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and supplied in Tris buffered saline with carrier protein containing 0.35% ProClin 950 as preservative. This antibody is utilized to perform a qualitative IHC assay to identify Progesterone Receptor (PR) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination. There are two configurations of the RTU antibody: 7 mL and 30 mL. • PR (16) Primary Antibody is provided in a Ready-to- Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection kit. The concentrated liquid format is for manual staining protocols. • The concentrated liquid antibody format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA. BOND-III Instrument • The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, IHC staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND K193393 - Page 4 of 14 application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP). B. Principle of Operation: Immunohistochemical techniques are used to demonstrate the presence of antigens in tissue and cells. The recommended staining protocol for PR (16) primary antibody is IHC Protocol F: Heat induced epitope retrieval is recommended using Bond Epitope Retrieval Solution 2 for 20 minutes. Bond Polymer Refine Detection utilizes a novel controlled polymerization technology to prepare polymeric HRP-linker antibody conjugates. Bond Polymer Refine Detection works as follows: • The specimen is incubated with hydrogen peroxide to quench endogenous peroxidase activity. • Bond RTU Primary Antibody PR (16) is applied. • A post primary antibody solution enhances penetration of the subsequent polymer reagent • A poly-HRP anti-mouse/rabbit IgG reagent localizes the primary antibody. • The substrate chromogen, 3,3’- diaminobenzidine (DAB), visualizes the complex via a brown precipitate. • Hematoxylin (blue) counterstaining allows the visualization of cell nuclei using Bond Polymer Refine Detection in combination with the automated BOND-MAX system reduces the possibility of human error and inherent variability resulting from individual reagent dilution, manual pipetting and reagent application. Table 1: PR IHC Staining Protocol F on BOND-III and BOND-MAX Instruments BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) IHC Protocol F 1 Peroxide Block Ambient 05:00 2 BOND Wash Solution Ambient 00:00 3 BOND Wash Solution Ambient 00:00 4 BOND Wash Solution Ambient 00:00 5 PRIMARY Antibody (PGR) Ambient 15:00 6 BOND Wash Solution Ambient 00:00 7 BOND Wash Solution Ambient 00:00 8 BOND Wash Solution Ambient 00:00 9 Post Primary Ambient 08:00 10 BOND Wash Solution Ambient 02:00 11 BOND Wash Solution Ambient 02:00 12 BOND Wash Solution Ambient 02:00 13 Polymer Detection Ambient 08:00 14 BOND Wash Solution Ambient 02:00 15 BOND Wash Solution Ambient 02:00 K193393 - Page 5 of 14 BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) 16 Deionized Water Ambient 00:00 17 Mixed DAB Refine Ambient 00:00 18 Mixed DAB Refine Ambient 10:00 19 Deionized Water Ambient 00:00 20 Deionized Water Ambient 00:00 Applicant:

idK193393_s0_e2000

K193393.txt

regulation section

21 CFR 864.1860 - Immunohistochemistry Reagents and Kits

03 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY I. Background Information: A. 510(k) Number K193393 B. Applicant Leica Biosystems Newcastle Ltd. C. Proprietary and Established Names BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) D. Regulatory Information Product Code(s) Classification Regulation Section Panel MXZ Class II 21 CFR 864.1860 - Immunohistochemistry Reagents and Kits II. Submission/Device Overview: A. Purpose for Submission: Leica Biosystems Newcastle Ltd., is submitting this traditional 510(k) notification to request modifications to their BOND™ Ready-to-Use (RTU) Primary Antibody Progesterone Receptor (16) and Concentrated Liquid Mouse Monoclonal Antibody (Novocastra™), previously cleared under K062615, K171753 and K183102 for the BOND-MAX instrument. The proposed modifications are for adding the following to the existing device: • BOND-III System (staining platform) • BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) (30mL) B. Measurand: K193393 - Page 2 of 14 Human Progesterone Receptor in formalin-fixed, paraffin embedded breast cancer tissue. C. Type of Test: Immunohistochemistry (IHC) III. Intended Use/Indications for Use: A. Intended Use(s): See Indications for Use below. B. Indication(s) for Use: Ready-to-Use Format For in vitro diagnostic use. BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) is a monoclonal antibody intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining using the automated BOND-MAX or BOND-III systems. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterne Receptor Clone (16) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. Progesterone Receptor Clone (16) is optimized for use on the Leica Biosystems automated BOND-MAX or BOND-III systems using the BOND Polymer Refine Detection kit. Concentrated Liquid Antibody Format For in vitro diagnostic use. Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone (16) (Concentrated Liquid Antibody Format) is intended to be used for the qualitative identification by light microscopy of human progesterone receptor in formalin-fixed, paraffin-embedded tissue by immunohistochemical staining. Progesterone Receptor Clone (16) specifically binds to the progesterone receptor antigen located in the nucleus of progesterone receptor positive normal and neoplastic cells. Progesterone Receptor Clone (16) Monoclonal Antibody (Concentrated Liquid Antibody Format) is indicated as an aid in the management, prognosis and prediction of therapy outcome of breast cancer. The clinical interpretation of any staining or its absence should be K193393 - Page 3 of 14 complemented by morphological studies using proper controls and should be evaluated within the context of the patient’s clinical history and other diagnostic tests by a qualified pathologist. C. Special Conditions for Use Statement(s): Rx - For Prescription Use Only D. Special Instrument Requirements: BOND-MAX and BOND-III staining platforms. IV. Device/System Characteristics: A. Device Description: BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) • Progesterone Receptor Clone (16) or PR (16) is a mouse anti-human monoclonal antibody produced as a tissue culture supernatant and supplied in Tris buffered saline with carrier protein containing 0.35% ProClin 950 as preservative. This antibody is utilized to perform a qualitative IHC assay to identify Progesterone Receptor (PR) expression in human breast cancer tissue routinely processed and paraffin-embedded for histological examination. There are two configurations of the RTU antibody: 7 mL and 30 mL. • PR (16) Primary Antibody is provided in a Ready-to- Use (RTU) and a concentrated liquid format. The RTU format is supplied in Tris buffered saline with carrier protein, containing 0.35% ProClin™ 950 as a preservative and is provided in two volumes (7 mL and 30 mL). The total protein concentration is approximately 10 mg/mL and the total antibody concentration is greater than or equal to 1 mg/L as determined by ELISA. The RTU format is optimally diluted for use on the automated BOND-MAX and BOND-III instrument staining platforms in combination with BOND Polymer Refine Detection kit. The concentrated liquid format is for manual staining protocols. • The concentrated liquid antibody format is a liquid tissue culture supernatant containing 15 mM sodium azide as a preservative. The total protein concentration is determined on a per batch basis and is described on the vial label, and the antibody concentration is greater than or equal to 324.0 mg/L as determined by ELISA. BOND-III Instrument • The BOND-MAX and BOND-III instruments are fully automated slide stainers that perform automated deparaffinization (dewaxing), antigen retrieval, IHC staining/in situ hybridization (ISH) staining, and counterstaining. The major components of the BOND staining platforms are the processing module, computer (BOND controller), handheld ID scanner, and slide label printer. The BOND staining platforms are composed of a number of discrete software components including the BOND K193393 - Page 4 of 14 application software, BOND instrument/processing module software, BOND service software, and Laboratory interface system - integration package (LIS-IP). B. Principle of Operation: Immunohistochemical techniques are used to demonstrate the presence of antigens in tissue and cells. The recommended staining protocol for PR (16) primary antibody is IHC Protocol F: Heat induced epitope retrieval is recommended using Bond Epitope Retrieval Solution 2 for 20 minutes. Bond Polymer Refine Detection utilizes a novel controlled polymerization technology to prepare polymeric HRP-linker antibody conjugates. Bond Polymer Refine Detection works as follows: • The specimen is incubated with hydrogen peroxide to quench endogenous peroxidase activity. • Bond RTU Primary Antibody PR (16) is applied. • A post primary antibody solution enhances penetration of the subsequent polymer reagent • A poly-HRP anti-mouse/rabbit IgG reagent localizes the primary antibody. • The substrate chromogen, 3,3’- diaminobenzidine (DAB), visualizes the complex via a brown precipitate. • Hematoxylin (blue) counterstaining allows the visualization of cell nuclei using Bond Polymer Refine Detection in combination with the automated BOND-MAX system reduces the possibility of human error and inherent variability resulting from individual reagent dilution, manual pipetting and reagent application. Table 1: PR IHC Staining Protocol F on BOND-III and BOND-MAX Instruments BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) IHC Protocol F 1 Peroxide Block Ambient 05:00 2 BOND Wash Solution Ambient 00:00 3 BOND Wash Solution Ambient 00:00 4 BOND Wash Solution Ambient 00:00 5 PRIMARY Antibody (PGR) Ambient 15:00 6 BOND Wash Solution Ambient 00:00 7 BOND Wash Solution Ambient 00:00 8 BOND Wash Solution Ambient 00:00 9 Post Primary Ambient 08:00 10 BOND Wash Solution Ambient 02:00 11 BOND Wash Solution Ambient 02:00 12 BOND Wash Solution Ambient 02:00 13 Polymer Detection Ambient 08:00 14 BOND Wash Solution Ambient 02:00 15 BOND Wash Solution Ambient 02:00 K193393 - Page 5 of 14 BOND Protocol Step No Reagent Temperature (°C) Incubation Time (min:sec) 16 Deionized Water Ambient 00:00 17 Mixed DAB Refine Ambient 00:00 18 Mixed DAB Refine Ambient 10:00 19 Deionized Water Ambient 00:00 20 Deionized Water Ambient 00:00 Regulation section:

idK193393_s2000_e4000

K193393.txt

predicate device name

BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16

ient 00:00 22 Hematoxylin Ambient 05:00 23 Deionized Water Ambient 00:00 24 BOND Wash Solution Ambient 00:00 25 Deionized Water Ambient 00:00 C. Instrument Description Information: Modes of Operation Yes No Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Software FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types. 1. Instrument Name: Leica BOND-III staining instrument. 2. Specimen Identification: Specimen identification is performed through the BOND Application Software which is the primary interface to the BOND instrument. 3. Specimen Sampling and Handling: Tissue sections (glass slides) are prepared from formalin-fixed, paraffin-embedded (FFPE) breast biopsy specimens. Slides are placed on the BOND-III staining instrument for staining with the BOND RTU Primary Antibody PR (16). 4. Calibration: The initial calibration of the staining instrument is performed by Leica Biosystems Melbourne Pty Ltd. manufacturing facility before shipping to the customer site. Leica field service engineers perform calibration and service through the BOND Service software. 5. Quality Control: K193393 - Page 6 of 14 Positive (endometrium or weakly positive breast carcinoma) and negative (tonsil) controls should be performed with each staining run. The pathologist is responsible for assuring that the assay is performing appropriately per instructions for use. V. Substantial Equivalence Information: A. Predicate Device Name(s): BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 B. Predicate 510(k) Number(s): K171753 C. Comparison with Predicate(s): Device & Predicate Device(s): K193393 K171753 Device Trade Name BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 (Concentrated Liquid Antibody Format) BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), Novocastra Liquid Mouse Monoclonal Antibody Progesterone Receptor Clone 16 General Device Characteristic Similarities Intended Use/Indications for Use Qualitative identification of human Progesterone Receptor in breast cancer patients Same Antibody Type Mouse monoclonal Same Isotype IgG1 Same PR Clone 16 Same Immunogen A prokaryotic recombinant protein corresponding to the N- terminal region of the A form of the human progesterone receptor Same Storage 2-80 C Same Technology Immunohistochemistry Same Tissue Type Formalin-fixed paraffin-embedded breast cancer tissue Same K193393 - Page 7 of 14 Staining Pattern Nuclear Same Staining Protocol IHC Protocol F Same General Device Characteristic Differences Staining Instrument BOND-III & BOND- MAX BOND-MAX RTU Antibody Progesterone Receptor (16) Configuration 7 mL & 30 mL 7 mL VI. Standards/Guidance Documents Referenced: 21 CFR 864.1860 – Immunohistochemistry reagents and kits VII. Performance Characteristics (if/when applicable): A. Analytical Performance: 1. Precision/Reproducibility: The sponsor conducted repeatability and reproducibility studies to support the performance of the device. Precision (Repeatability) The objective of this study was to evaluate the precision (repeatability) of the Leica BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) on BOND-III instrument. a. Within-run repeatability The within-run study involved testing of sectioned slides from 6 unique FFPE breast tumor tissue specimens. The slides consisted of 3 PR negative specimens and 3 PR positive specimens including 1 PR staining around the cut-off (1-10% staining). The study was conducted using one reagent lot on one BOND-III instrument at one laboratory testing site. Three replicates from each of the 6 unique breast tumor tissue cases plus a tissue control slide were stained. Acceptance Criteria: All PR negative cases must be scored negative using the recommended retrieval protocol conditions. All PR low positive cases must be scored low positive using the recommended retrieval protocol conditions. All PR high positive cases must be scored high positive using the recommended retrieval protocol conditions. Table 2: Within-run Repeatability Study Results PPA NPA OPA Estimate (count) 95% CI Estimate (count) 95% CI Estimate (count) 95% CI K193393 - Page 8 of 14 Run 1 94.4% (17/18) [74.2 – 99.0%] 88.9% (8/9) [56.5 – 98.0%] 92.6% (25/27*) [76.6 - 97.9%] Run 2 100% (9/9) [70.1 – 100%] 100% (17/17) [81.6 – 100%] 100% (26/26) [87.1 – 100%] Overall 96.3% (26/27) [81.7 - 99.3%] 96.2% (25/26) [81.1 - 99.3%] 96.2% (51/53*) [87.2 – 99.0%] *1 slide could not be assessed by the pathologist due to background staining obscuring the nuclei. PPA: Positive percent agreement; NPA: Negative percent agreement; OPA: Overall percent agreement Results: As shown in Table 2, the Overall Percent Agreement (OPA) was 96.2% (51/53; 95% CI: 87.2% to 99.0%), with Positive Percent Agreement (PPA) of 96.3% (26/27; 95% CI: 81.7% – 99.3%), and Negative Percent Agreement (NPA) of 96.2% (25/26; 95% CI: 81.1% – 99.3%). The study results are acceptable. b. Between-day repeatability The between-day study involved testing of sectioned slides from 27 unique FFPE breast tumor tissue specimens. The slides consisted of 13 PR negative specimens, 14 PR positive specimens including 5 PR low positive tissue specimens (1-10% staining). The study was conducted using three BOND-III instruments at one laboratory-testing site. One sectioned slide from each unique breast tumor tissue case (total 27) and three tissue control slides, one per Slide Staining Assembly (SSA) were stained with Lot 1 on Days 1 and 2, Lot 2 on Days 3 and 4, and Lot 3 on Days 5 and 6 on a single BOND-III instrument. Each unique breast tissue case was also stained using 2 additional instruments such that the lots and days tested were varied. BOND-III instrument has 30 slide positions allowing for 9 unique cases and a tissue control to be run on each SSA and for all 27 cases to be stained in a single run. Each day a single case was stained 3 times, once on each of the three instruments. In total, using 3 SSAs per instrument and 3 instruments, 486 measurements were generated (3 instruments x 3 SSAs x 9 slides x 6 days) . Acceptance Criteria for between-days, between-instruments, between lots, between pathologists and between laboratories studies are as follows: The Overall Agreement (OA), Positive Agreement (PA) and Negative Agreement (NA), shall be 85% of the lower bound of the two-sided 95% CI when the following sources of potential variability are studied: between-days, between-instruments, between-lots, between-pathologists and between-laboratories. Note: samples used in between-day, between-instrument and between-lot repeatability studies were pre-screened, pre-characterized and scored by an independent scorer. Table 3: Between-day Repeatability Study Results PPA NPA OPA Estimate (count) 95% CI Estimate (count) 95% CI Estimate (count) 95% CI Day1 100% (33/33) [89.6 – 100%] 91.5% (43/47) [80.1 - 96.6%] 95% (76/80*) [87.8 – 98.0%] Day2 100% (33/33) [89.6 – 100%] 95.8% (46/48) [86.0 - 98.8%] 97.5% (79/81) [91.4 - 99.3%] Day3 100% (33/33) [89.6 – 100%] 100% (48/48) [92.6 – 100%] 100% (81/81) [95.5 – 100%] Day4 100% (33/33) [89.6 – 100%] 100% (48/48) [92.6 – 100%] 100% (81/81) [95.5 – 100%] K193393 - Page 9 of 14 Day5 100% (33/33) [89.6 – 100%] 100% Predicate device name:

idK193393_s6000_e8000

K193393.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

[93.3%-97.3%] ANA 174 184 94.6% [92.0%-96.7%] AOA 384 404 95.0% [92.8%-97.0%] Pathologist 2 vs 3 APA 196 211 92.9% [90.2%-95.3%] ANA 178 193 92.2% [89.2%-94.8%] AOA 374 404 92.6% [89.9%-95.0%] All pathologists APA 602 640 94.1% [92.0%-95.8%] ANA 534 572 93.4% [91.1%-95.3%] AOA 1136 1212 93.7% [91.7%-95.5%] Note: Number of pairs for APA and ANA were averaged between the comparison groups (average of row and column sums) since neither one is the reference. Results: As shown in Table 6, the average positive, negative, and overall percent agreements were 94.1%, 93.4% and 93.7%, respectively. The results met the study acceptance criteria. Table 7: Reproducibility Study: Between-laboratory Agreement of PGR Status by PGR B- RTU Antibody on BOND-III – Primary Analyses: Laboratories Measure Number of Agreements Number of Pairs % Agreement 95 % CI Lab 1 vs 2 APA 203 211 96.2% [94.2%-98.0%] ANA 183 191 95.8% [93.6%-97.7%] AOA 386 402 96.0% [94.0%-97.8%] Lab 1 vs 3 APA 206 215 95.8% [93.7%-97.6%] ANA 181 190 95.3% [92.9%-97.3%] AOA 387 405 95.6% [93.6%-97.5%] Lab 2 vs 3 APA 206 213.5 96.5% [94.6%-98.2%} ANA 181 188.5 96.0% [93.9%-97.9%] AOA 387 402 96.3% [94.3%-98.0%] K193393 - Page 12 of 14 All Labs APA 615 693.5 96.2% [94.5%-97.6%] ANA 545 569.5 95.7% [93.9%-97.3%] AOA 1160 1209 95.9% [94.3%-97.4%] Note: Number of pairs for APA and ANA were averaged between the comparison groups (average of row and column sums) since neither one is the reference. Results: As shown in Table 7, the average positive, negative, and overall percent agreements were 96.2%, 95.7%, and 95.9%, respectively. These results met the study acceptance criteria. 2. Linearity: Not applicable. 3. Analytical Specificity/Interference: Analytical specificity and interference studies were provided in the original 510k notification. Please refer to K062615 for more details. 4. Assay Reportable Range: Not applicable. 5. Stability, Expected Values (Controls, Calibrators, or Methods): The original stability studies on BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), 7 mL, were submitted in K062615. The sponsor submitted the continued stability studies on the existing 7 mL, and the additional stability studies and justification on the new 30 mL configuration, including real-time, transport, in use and cut section stability studies in Section 14 of the K193393: Three batches (lots) of antibody in immediate packaging (batches 1, 2 and 3) were manufactured and then stored under recommended storage conditions (40C). All three lots were used in the Real-Time Stability Test to determine the shelf-life of the BOND Ready-to-Use Primary Antibody Progesterone Receptor (16). In addition to Real-Time Stability testing, all units of batch 1 underwent a transport simulation test. Following the completion of the transport simulation test, units from lot 1 were used for the In-Use test and the Accelerated Stability Testing. Stability studies were performed on both BOND-MAX and BOND-III systems. Results and Conclusion: • Stability study data support the claim for 7 mL Bond RTU Primary Antibody Progesterone Receptor (16), for shelf life of 18 months (545 days) from the point of manufacture when stored at 2-8°C. • Stability study data support the claim for 30 mL Bond RTU Primary Antibody Progesterone Receptor (16), for shelf life of 18 months (545 days) from the point of manufacture when stored at 2-8°C. 6. Detection Limit: Not applicable. 7. Assay Cut-Off: K193393 - Page 13 of 14 Scoring: Test results are considered as positive when ≥1% of tumor nuclei are immunoreactive (positive staining) for progesterone receptor and negative when <1% of tumor cells are immunoreactive for progesterone receptor. 8. Accuracy (Instrument): Not applicable. 9. Carry-Over: Not applicable. B. Comparison Studies: a. Method Comparison with the Predicate Device: The objective of the method comparison study was to evaluate the concordance of results obtained using BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) on BOND- III (subject device), with results obtained using BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), (K171753), on BOND-MAX (predicate device, K062615). The study was conducted at three laboratory-testing sites. Each site tested 152 of 456 unique FFPE breast whole tissue sections on the BOND-III instrument, and 152 on the BOND-MAX (two unstained slides were received per each of 152 specimens). One trained pathologist interpreted the stained slides at each site. Positive (endometrium) and negative (tonsil) tissue controls were used in the study. Scoring: Tissue is considered “PR Positive” when ≥1% of tumor nuclei are immunoreactive for PR. When <1% of tumor cells are immunoreactive for PR, the tissue is considered “PR Negative”. Acceptance criteria: The lower bounds of the 2-sided 95% confidence interval BOND-III of the OPA, PPA and NPA shall be ≥ 85% when using BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) on BOND-III compared to BOND-MAX. Table 8: Method Comparison Study: Percent Agreement Between PR Status by BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) on BOND-III and BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) on BOND-MAX – Primary Analysis: Measure Number of Agreements Number of Pairs % Agreement 95% CI PPA 213 223 95.5% [91.9% - 97.5%] NPA 222 232 95.7% [92.2% - 97.6%] OPA 435 455 95.6% [93.3% - 97.1%] Table 9: Method Comparison Study: 2 by 2 Contingency Table – Primary Analysis BOND-MAX Negative Positive Total BO ND -III Negative 222 10 232 K193393 - Page 14 of 14 Positive 10 213 223 Total 232 223 455 Results: As shown in Table 8, the positive, negative and overall percent agreement were 95.5%, 95.7% and 95.6%, respectively. These results indicate PR (16) staining using the BOND-III is comparable to PR (16) staining using the BOND-MAX. b. Matrix Comparison: Not applicable. C. Clinical Studies: a. Clinical Sensitivity: Not applicable. b. Clinical Specificity: Not applicable. c. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable. D. Clinical Cut-Off: Tissue is considered as positive” when ≥1% of tumor nuclei are immunoreactive (positive staining), and negative when <1% of tumor cells are immunoreactive for progesterone receptor. E. Expected Values/Reference Range: Not applicable. F. Other Supportive Instrument Performance Characteristics Data: Not applicable. VIII. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. IX. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK193393_s6000_e8000

K193393.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

5% [93.3%-97.3%] ANA 174 184 94.6% [92.0%-96.7%] AOA 384 404 95.0% [92.8%-97.0%] Pathologist 2 vs 3 APA 196 211 92.9% [90.2%-95.3%] ANA 178 193 92.2% [89.2%-94.8%] AOA 374 404 92.6% [89.9%-95.0%] All pathologists APA 602 640 94.1% [92.0%-95.8%] ANA 534 572 93.4% [91.1%-95.3%] AOA 1136 1212 93.7% [91.7%-95.5%] Note: Number of pairs for APA and ANA were averaged between the comparison groups (average of row and column sums) since neither one is the reference. Results: As shown in Table 6, the average positive, negative, and overall percent agreements were 94.1%, 93.4% and 93.7%, respectively. The results met the study acceptance criteria. Table 7: Reproducibility Study: Between-laboratory Agreement of PGR Status by PGR B- RTU Antibody on BOND-III – Primary Analyses: Laboratories Measure Number of Agreements Number of Pairs % Agreement 95 % CI Lab 1 vs 2 APA 203 211 96.2% [94.2%-98.0%] ANA 183 191 95.8% [93.6%-97.7%] AOA 386 402 96.0% [94.0%-97.8%] Lab 1 vs 3 APA 206 215 95.8% [93.7%-97.6%] ANA 181 190 95.3% [92.9%-97.3%] AOA 387 405 95.6% [93.6%-97.5%] Lab 2 vs 3 APA 206 213.5 96.5% [94.6%-98.2%} ANA 181 188.5 96.0% [93.9%-97.9%] AOA 387 402 96.3% [94.3%-98.0%] K193393 - Page 12 of 14 All Labs APA 615 693.5 96.2% [94.5%-97.6%] ANA 545 569.5 95.7% [93.9%-97.3%] AOA 1160 1209 95.9% [94.3%-97.4%] Note: Number of pairs for APA and ANA were averaged between the comparison groups (average of row and column sums) since neither one is the reference. Results: As shown in Table 7, the average positive, negative, and overall percent agreements were 96.2%, 95.7%, and 95.9%, respectively. These results met the study acceptance criteria. 2. Linearity: Not applicable. 3. Analytical Specificity/Interference: Analytical specificity and interference studies were provided in the original 510k notification. Please refer to K062615 for more details. 4. Assay Reportable Range: Not applicable. 5. Stability, Expected Values (Controls, Calibrators, or Methods): The original stability studies on BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), 7 mL, were submitted in K062615. The sponsor submitted the continued stability studies on the existing 7 mL, and the additional stability studies and justification on the new 30 mL configuration, including real-time, transport, in use and cut section stability studies in Section 14 of the K193393: Three batches (lots) of antibody in immediate packaging (batches 1, 2 and 3) were manufactured and then stored under recommended storage conditions (40C). All three lots were used in the Real-Time Stability Test to determine the shelf-life of the BOND Ready-to-Use Primary Antibody Progesterone Receptor (16). In addition to Real-Time Stability testing, all units of batch 1 underwent a transport simulation test. Following the completion of the transport simulation test, units from lot 1 were used for the In-Use test and the Accelerated Stability Testing. Stability studies were performed on both BOND-MAX and BOND-III systems. Results and Conclusion: • Stability study data support the claim for 7 mL Bond RTU Primary Antibody Progesterone Receptor (16), for shelf life of 18 months (545 days) from the point of manufacture when stored at 2-8°C. • Stability study data support the claim for 30 mL Bond RTU Primary Antibody Progesterone Receptor (16), for shelf life of 18 months (545 days) from the point of manufacture when stored at 2-8°C. 6. Detection Limit: Not applicable. 7. Assay Cut-Off: K193393 - Page 13 of 14 Scoring: Test results are considered as positive when ≥1% of tumor nuclei are immunoreactive (positive staining) for progesterone receptor and negative when <1% of tumor cells are immunoreactive for progesterone receptor. 8. Accuracy (Instrument): Not applicable. 9. Carry-Over: Not applicable. B. Comparison Studies: a. Method Comparison with the Predicate Device: The objective of the method comparison study was to evaluate the concordance of results obtained using BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) on BOND- III (subject device), with results obtained using BOND Ready-to-Use Primary Antibody Progesterone Receptor (16), (K171753), on BOND-MAX (predicate device, K062615). The study was conducted at three laboratory-testing sites. Each site tested 152 of 456 unique FFPE breast whole tissue sections on the BOND-III instrument, and 152 on the BOND-MAX (two unstained slides were received per each of 152 specimens). One trained pathologist interpreted the stained slides at each site. Positive (endometrium) and negative (tonsil) tissue controls were used in the study. Scoring: Tissue is considered “PR Positive” when ≥1% of tumor nuclei are immunoreactive for PR. When <1% of tumor cells are immunoreactive for PR, the tissue is considered “PR Negative”. Acceptance criteria: The lower bounds of the 2-sided 95% confidence interval BOND-III of the OPA, PPA and NPA shall be ≥ 85% when using BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) on BOND-III compared to BOND-MAX. Table 8: Method Comparison Study: Percent Agreement Between PR Status by BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) on BOND-III and BOND Ready-to-Use Primary Antibody Progesterone Receptor (16) on BOND-MAX – Primary Analysis: Measure Number of Agreements Number of Pairs % Agreement 95% CI PPA 213 223 95.5% [91.9% - 97.5%] NPA 222 232 95.7% [92.2% - 97.6%] OPA 435 455 95.6% [93.3% - 97.1%] Table 9: Method Comparison Study: 2 by 2 Contingency Table – Primary Analysis BOND-MAX Negative Positive Total BO ND -III Negative 222 10 232 K193393 - Page 14 of 14 Positive 10 213 223 Total 232 223 455 Results: As shown in Table 8, the positive, negative and overall percent agreement were 95.5%, 95.7% and 95.6%, respectively. These results indicate PR (16) staining using the BOND-III is comparable to PR (16) staining using the BOND-MAX. b. Matrix Comparison: Not applicable. C. Clinical Studies: a. Clinical Sensitivity: Not applicable. b. Clinical Specificity: Not applicable. c. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable. D. Clinical Cut-Off: Tissue is considered as positive” when ≥1% of tumor nuclei are immunoreactive (positive staining), and negative when <1% of tumor cells are immunoreactive for progesterone receptor. E. Expected Values/Reference Range: Not applicable. F. Other Supportive Instrument Performance Characteristics Data: Not applicable. VIII. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. IX. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK173202_s0_e2000

K173202.txt

purpose for submission

New device

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K173202 B. Purpose for Submission: New device C. Measurand: Antithrombin activity (%) D. Type of Test: Quantitative chromogenic test E. Applicant: Sekisui Medical Co., LTD F. Proprietary and Established Names: CP3000 Coagulation Analyzer Coagpia AT Reagent Coagpia Calibrator Coagpia Control Set G. Regulatory Information: 1. Regulation section: Device Regulation Section CP3000 Coagulation Analyzer 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagpia AT Reagent 21 CFR 864.7060, Antithrombin III Assay Coagpia Calibrator 21 CFR 862.1150 Calibrator Coagpia Control Set 21 CFR 864.5425, Plasma, coagulation control 2. Classification: Class II 2 3. Product code: Device Product Code CP3000 Coagulation Analyzer JPA Coagpia AT Reagent JBQ Coagpia Calibrator JIX Coagpia Control Set GGN 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): CP3000 Coagulation Analyzer The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. Coagpia Calibrator The Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent Coagpia Control Set The Coagpia Control set contains 2 levels of assayed plasma intended for the quality control of the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel. For in vitro diagnostic use. · Coagpia AT Reagent 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: CP3000 Coagulation Analyzer I. Device Description: CP3000 Coagulation Analyzer The CP3000 is an automated blood coagulation instrument which performs tests for specific parameters in citrated human plasma. The CP3000 system is capable of performing chromogenic assays, which allows analysis for both direct hemostasis measurements and calculated parameters. For this assay methodology, the analyzer employs two photometric detection methods: light scattering and absorbance. The light scattering method uses light emitting diodes at a wavelength of 660 nm, and the absorbance method uses a halogen lamp with filters providing wavelengths at 405, 570, and 730 nm. The analyzer components include the analyzer hardware and its controlling software (firmware), a personal computer (PC) with its user interface, result calculations, and patient data management software. The PC also provides the software to communicate with the host Laboratory Information System (LIS). Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human plasma on the CP3000 analyzer. R1 contains bovine Factor Xa, heparin sodium salt (porcine), buffer, surfactant and preservative. R2 contains a protease substrate N- acetyl-D-arginyl-glycyl-L-arginyl-p-nitroanilide, buffer, surfactant and preservative. Both reagents are liquid and do not require any preparation prior to use. Coagpia Calibrator The Coagpia Calibrator is lyophilized human plasma and is suitable for the calibration of the antithrombin activity assay using Coagpia AT Reagent on the CP3000 coagulation analyzer. Coagpia Control Set The Coagpia Control Set is lyophilized human plasma supplied as two levels (Level 1 Control and Level 2 Control) and is suitable for use with the antithrombin activity assay using Coagpia AT Reagent on the CP3000 analyzer. J. Substantial Equivalence Information: 1. Predicate device name(s) and 510(k) numbers: Predicate Device Predicate 510(k) Number ACL TOP 700 LAS K160276 HemosIL Liquid Antithrombin K062431 HemosIL Calibration Plasma K041905 HemosIL Normal Control Assayed K021023 4 Predicate Device Predicate 510(k) Number HemosIL Low Abnormal Control Assayed K021024 2. Comparison with predicate: CP3000 Coagulation Analyzer Similarities Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Intended use The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. The ACL TOP is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The system provides results for both direct hemostasis measurement and calculated parameters. Interface · Touch screen operation Windows 7 Operating System Same Options Available with closed tube sampling (CTS) function Same Analytes Multiple Same Reagent Handling · Refrigerated on board · Internal bar code sample identification Same Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Application type · Chromogenic · Coagulometric (turbidimetric) · Measurement Chromogenic (absorbance) measurement · Immunological measurement 5 Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Detection Photometric · Absorbance · Light scattering Photometric · Absorbance Wavelengths · 405 nm · 570 nm · 660 nm · 730 nm · 405 nm · 671 nm Throughput (non- CTS) Up to 400 clotting tests/hour Up to 330 PT and APTT tests/hour Coagpia AT Reagent Similarities Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Intended use Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. HemoslL Liquid Antithrombin is an automated chromogenic assay for the quantitative determination of Antithrombin in human citrated plasma as an aid in the diagnosis of hereditary and acquired Antithrombin deficiency and to monitor Antithrombin substitution therapy. This in vitro diagnostic test is based on a synthetic chromogenic substrate and on Factor Xa inactivation. As a consequence, it is specific and not influenced by Heparin Cofactor II. Antithrombin levels in patient plasma are measured automatically on IL Coagulation Systems. Analyte Antithrombin Same Reagent State Liquid, ready to use Same Method Chromogenic Same Detection Photometric Same 6 Differences Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Key Components · Factor Xa (bovine) · Heparin N-Acetyl-D-arginyl-glycyl-L- arginyl- p-nitroanilide dihydrochloride (chromogenic substrate) · Factor Xa (bovine) · Heparin N-α-Z-D-Arg-Gly-Arg- pNA·2HCl (chromogenic substrate) Sample Type Human citrated plasma Human citrated plasma Expected Values 89–131% 83−128% Repeatability 0.7–2.9% 2.2–7.4% Within Laboratory Precision 1.1–5.8% 3.1–8.6% Linearity 14–140% 10–150% Clinical reportable range 14–150% 10–150% Coagpia Calibrator Similarities Item Device Coagpia Calibrator Predicate HemosIL Calibration Plasma Intended use Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent HemosIL Calibration plasma is intended Purpose for submission:

idK173202_s0_e2000

K173202.txt

measurand

Antithrombin activity (%)

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K173202 B. Purpose for Submission: New device C. Measurand: Antithrombin activity (%) D. Type of Test: Quantitative chromogenic test E. Applicant: Sekisui Medical Co., LTD F. Proprietary and Established Names: CP3000 Coagulation Analyzer Coagpia AT Reagent Coagpia Calibrator Coagpia Control Set G. Regulatory Information: 1. Regulation section: Device Regulation Section CP3000 Coagulation Analyzer 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagpia AT Reagent 21 CFR 864.7060, Antithrombin III Assay Coagpia Calibrator 21 CFR 862.1150 Calibrator Coagpia Control Set 21 CFR 864.5425, Plasma, coagulation control 2. Classification: Class II 2 3. Product code: Device Product Code CP3000 Coagulation Analyzer JPA Coagpia AT Reagent JBQ Coagpia Calibrator JIX Coagpia Control Set GGN 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): CP3000 Coagulation Analyzer The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. Coagpia Calibrator The Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent Coagpia Control Set The Coagpia Control set contains 2 levels of assayed plasma intended for the quality control of the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel. For in vitro diagnostic use. · Coagpia AT Reagent 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: CP3000 Coagulation Analyzer I. Device Description: CP3000 Coagulation Analyzer The CP3000 is an automated blood coagulation instrument which performs tests for specific parameters in citrated human plasma. The CP3000 system is capable of performing chromogenic assays, which allows analysis for both direct hemostasis measurements and calculated parameters. For this assay methodology, the analyzer employs two photometric detection methods: light scattering and absorbance. The light scattering method uses light emitting diodes at a wavelength of 660 nm, and the absorbance method uses a halogen lamp with filters providing wavelengths at 405, 570, and 730 nm. The analyzer components include the analyzer hardware and its controlling software (firmware), a personal computer (PC) with its user interface, result calculations, and patient data management software. The PC also provides the software to communicate with the host Laboratory Information System (LIS). Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human plasma on the CP3000 analyzer. R1 contains bovine Factor Xa, heparin sodium salt (porcine), buffer, surfactant and preservative. R2 contains a protease substrate N- acetyl-D-arginyl-glycyl-L-arginyl-p-nitroanilide, buffer, surfactant and preservative. Both reagents are liquid and do not require any preparation prior to use. Coagpia Calibrator The Coagpia Calibrator is lyophilized human plasma and is suitable for the calibration of the antithrombin activity assay using Coagpia AT Reagent on the CP3000 coagulation analyzer. Coagpia Control Set The Coagpia Control Set is lyophilized human plasma supplied as two levels (Level 1 Control and Level 2 Control) and is suitable for use with the antithrombin activity assay using Coagpia AT Reagent on the CP3000 analyzer. J. Substantial Equivalence Information: 1. Predicate device name(s) and 510(k) numbers: Predicate Device Predicate 510(k) Number ACL TOP 700 LAS K160276 HemosIL Liquid Antithrombin K062431 HemosIL Calibration Plasma K041905 HemosIL Normal Control Assayed K021023 4 Predicate Device Predicate 510(k) Number HemosIL Low Abnormal Control Assayed K021024 2. Comparison with predicate: CP3000 Coagulation Analyzer Similarities Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Intended use The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. The ACL TOP is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The system provides results for both direct hemostasis measurement and calculated parameters. Interface · Touch screen operation Windows 7 Operating System Same Options Available with closed tube sampling (CTS) function Same Analytes Multiple Same Reagent Handling · Refrigerated on board · Internal bar code sample identification Same Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Application type · Chromogenic · Coagulometric (turbidimetric) · Measurement Chromogenic (absorbance) measurement · Immunological measurement 5 Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Detection Photometric · Absorbance · Light scattering Photometric · Absorbance Wavelengths · 405 nm · 570 nm · 660 nm · 730 nm · 405 nm · 671 nm Throughput (non- CTS) Up to 400 clotting tests/hour Up to 330 PT and APTT tests/hour Coagpia AT Reagent Similarities Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Intended use Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. HemoslL Liquid Antithrombin is an automated chromogenic assay for the quantitative determination of Antithrombin in human citrated plasma as an aid in the diagnosis of hereditary and acquired Antithrombin deficiency and to monitor Antithrombin substitution therapy. This in vitro diagnostic test is based on a synthetic chromogenic substrate and on Factor Xa inactivation. As a consequence, it is specific and not influenced by Heparin Cofactor II. Antithrombin levels in patient plasma are measured automatically on IL Coagulation Systems. Analyte Antithrombin Same Reagent State Liquid, ready to use Same Method Chromogenic Same Detection Photometric Same 6 Differences Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Key Components · Factor Xa (bovine) · Heparin N-Acetyl-D-arginyl-glycyl-L- arginyl- p-nitroanilide dihydrochloride (chromogenic substrate) · Factor Xa (bovine) · Heparin N-α-Z-D-Arg-Gly-Arg- pNA·2HCl (chromogenic substrate) Sample Type Human citrated plasma Human citrated plasma Expected Values 89–131% 83−128% Repeatability 0.7–2.9% 2.2–7.4% Within Laboratory Precision 1.1–5.8% 3.1–8.6% Linearity 14–140% 10–150% Clinical reportable range 14–150% 10–150% Coagpia Calibrator Similarities Item Device Coagpia Calibrator Predicate HemosIL Calibration Plasma Intended use Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent HemosIL Calibration plasma is intended Measurand:

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K173202.txt

type of test

Quantitative chromogenic test

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K173202 B. Purpose for Submission: New device C. Measurand: Antithrombin activity (%) D. Type of Test: Quantitative chromogenic test E. Applicant: Sekisui Medical Co., LTD F. Proprietary and Established Names: CP3000 Coagulation Analyzer Coagpia AT Reagent Coagpia Calibrator Coagpia Control Set G. Regulatory Information: 1. Regulation section: Device Regulation Section CP3000 Coagulation Analyzer 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagpia AT Reagent 21 CFR 864.7060, Antithrombin III Assay Coagpia Calibrator 21 CFR 862.1150 Calibrator Coagpia Control Set 21 CFR 864.5425, Plasma, coagulation control 2. Classification: Class II 2 3. Product code: Device Product Code CP3000 Coagulation Analyzer JPA Coagpia AT Reagent JBQ Coagpia Calibrator JIX Coagpia Control Set GGN 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): CP3000 Coagulation Analyzer The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. Coagpia Calibrator The Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent Coagpia Control Set The Coagpia Control set contains 2 levels of assayed plasma intended for the quality control of the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel. For in vitro diagnostic use. · Coagpia AT Reagent 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: CP3000 Coagulation Analyzer I. Device Description: CP3000 Coagulation Analyzer The CP3000 is an automated blood coagulation instrument which performs tests for specific parameters in citrated human plasma. The CP3000 system is capable of performing chromogenic assays, which allows analysis for both direct hemostasis measurements and calculated parameters. For this assay methodology, the analyzer employs two photometric detection methods: light scattering and absorbance. The light scattering method uses light emitting diodes at a wavelength of 660 nm, and the absorbance method uses a halogen lamp with filters providing wavelengths at 405, 570, and 730 nm. The analyzer components include the analyzer hardware and its controlling software (firmware), a personal computer (PC) with its user interface, result calculations, and patient data management software. The PC also provides the software to communicate with the host Laboratory Information System (LIS). Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human plasma on the CP3000 analyzer. R1 contains bovine Factor Xa, heparin sodium salt (porcine), buffer, surfactant and preservative. R2 contains a protease substrate N- acetyl-D-arginyl-glycyl-L-arginyl-p-nitroanilide, buffer, surfactant and preservative. Both reagents are liquid and do not require any preparation prior to use. Coagpia Calibrator The Coagpia Calibrator is lyophilized human plasma and is suitable for the calibration of the antithrombin activity assay using Coagpia AT Reagent on the CP3000 coagulation analyzer. Coagpia Control Set The Coagpia Control Set is lyophilized human plasma supplied as two levels (Level 1 Control and Level 2 Control) and is suitable for use with the antithrombin activity assay using Coagpia AT Reagent on the CP3000 analyzer. J. Substantial Equivalence Information: 1. Predicate device name(s) and 510(k) numbers: Predicate Device Predicate 510(k) Number ACL TOP 700 LAS K160276 HemosIL Liquid Antithrombin K062431 HemosIL Calibration Plasma K041905 HemosIL Normal Control Assayed K021023 4 Predicate Device Predicate 510(k) Number HemosIL Low Abnormal Control Assayed K021024 2. Comparison with predicate: CP3000 Coagulation Analyzer Similarities Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Intended use The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. The ACL TOP is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The system provides results for both direct hemostasis measurement and calculated parameters. Interface · Touch screen operation Windows 7 Operating System Same Options Available with closed tube sampling (CTS) function Same Analytes Multiple Same Reagent Handling · Refrigerated on board · Internal bar code sample identification Same Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Application type · Chromogenic · Coagulometric (turbidimetric) · Measurement Chromogenic (absorbance) measurement · Immunological measurement 5 Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Detection Photometric · Absorbance · Light scattering Photometric · Absorbance Wavelengths · 405 nm · 570 nm · 660 nm · 730 nm · 405 nm · 671 nm Throughput (non- CTS) Up to 400 clotting tests/hour Up to 330 PT and APTT tests/hour Coagpia AT Reagent Similarities Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Intended use Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. HemoslL Liquid Antithrombin is an automated chromogenic assay for the quantitative determination of Antithrombin in human citrated plasma as an aid in the diagnosis of hereditary and acquired Antithrombin deficiency and to monitor Antithrombin substitution therapy. This in vitro diagnostic test is based on a synthetic chromogenic substrate and on Factor Xa inactivation. As a consequence, it is specific and not influenced by Heparin Cofactor II. Antithrombin levels in patient plasma are measured automatically on IL Coagulation Systems. Analyte Antithrombin Same Reagent State Liquid, ready to use Same Method Chromogenic Same Detection Photometric Same 6 Differences Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Key Components · Factor Xa (bovine) · Heparin N-Acetyl-D-arginyl-glycyl-L- arginyl- p-nitroanilide dihydrochloride (chromogenic substrate) · Factor Xa (bovine) · Heparin N-α-Z-D-Arg-Gly-Arg- pNA·2HCl (chromogenic substrate) Sample Type Human citrated plasma Human citrated plasma Expected Values 89–131% 83−128% Repeatability 0.7–2.9% 2.2–7.4% Within Laboratory Precision 1.1–5.8% 3.1–8.6% Linearity 14–140% 10–150% Clinical reportable range 14–150% 10–150% Coagpia Calibrator Similarities Item Device Coagpia Calibrator Predicate HemosIL Calibration Plasma Intended use Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent HemosIL Calibration plasma is intended Type of test:

idK173202_s0_e2000

K173202.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K173202 B. Purpose for Submission: New device C. Measurand: Antithrombin activity (%) D. Type of Test: Quantitative chromogenic test E. Applicant: Sekisui Medical Co., LTD F. Proprietary and Established Names: CP3000 Coagulation Analyzer Coagpia AT Reagent Coagpia Calibrator Coagpia Control Set G. Regulatory Information: 1. Regulation section: Device Regulation Section CP3000 Coagulation Analyzer 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagpia AT Reagent 21 CFR 864.7060, Antithrombin III Assay Coagpia Calibrator 21 CFR 862.1150 Calibrator Coagpia Control Set 21 CFR 864.5425, Plasma, coagulation control 2. Classification: Class II 2 3. Product code: Device Product Code CP3000 Coagulation Analyzer JPA Coagpia AT Reagent JBQ Coagpia Calibrator JIX Coagpia Control Set GGN 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): CP3000 Coagulation Analyzer The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. Coagpia Calibrator The Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent Coagpia Control Set The Coagpia Control set contains 2 levels of assayed plasma intended for the quality control of the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel. For in vitro diagnostic use. · Coagpia AT Reagent 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: CP3000 Coagulation Analyzer I. Device Description: CP3000 Coagulation Analyzer The CP3000 is an automated blood coagulation instrument which performs tests for specific parameters in citrated human plasma. The CP3000 system is capable of performing chromogenic assays, which allows analysis for both direct hemostasis measurements and calculated parameters. For this assay methodology, the analyzer employs two photometric detection methods: light scattering and absorbance. The light scattering method uses light emitting diodes at a wavelength of 660 nm, and the absorbance method uses a halogen lamp with filters providing wavelengths at 405, 570, and 730 nm. The analyzer components include the analyzer hardware and its controlling software (firmware), a personal computer (PC) with its user interface, result calculations, and patient data management software. The PC also provides the software to communicate with the host Laboratory Information System (LIS). Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human plasma on the CP3000 analyzer. R1 contains bovine Factor Xa, heparin sodium salt (porcine), buffer, surfactant and preservative. R2 contains a protease substrate N- acetyl-D-arginyl-glycyl-L-arginyl-p-nitroanilide, buffer, surfactant and preservative. Both reagents are liquid and do not require any preparation prior to use. Coagpia Calibrator The Coagpia Calibrator is lyophilized human plasma and is suitable for the calibration of the antithrombin activity assay using Coagpia AT Reagent on the CP3000 coagulation analyzer. Coagpia Control Set The Coagpia Control Set is lyophilized human plasma supplied as two levels (Level 1 Control and Level 2 Control) and is suitable for use with the antithrombin activity assay using Coagpia AT Reagent on the CP3000 analyzer. J. Substantial Equivalence Information: 1. Predicate device name(s) and 510(k) numbers: Predicate Device Predicate 510(k) Number ACL TOP 700 LAS K160276 HemosIL Liquid Antithrombin K062431 HemosIL Calibration Plasma K041905 HemosIL Normal Control Assayed K021023 4 Predicate Device Predicate 510(k) Number HemosIL Low Abnormal Control Assayed K021024 2. Comparison with predicate: CP3000 Coagulation Analyzer Similarities Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Intended use The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. The ACL TOP is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The system provides results for both direct hemostasis measurement and calculated parameters. Interface · Touch screen operation Windows 7 Operating System Same Options Available with closed tube sampling (CTS) function Same Analytes Multiple Same Reagent Handling · Refrigerated on board · Internal bar code sample identification Same Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Application type · Chromogenic · Coagulometric (turbidimetric) · Measurement Chromogenic (absorbance) measurement · Immunological measurement 5 Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Detection Photometric · Absorbance · Light scattering Photometric · Absorbance Wavelengths · 405 nm · 570 nm · 660 nm · 730 nm · 405 nm · 671 nm Throughput (non- CTS) Up to 400 clotting tests/hour Up to 330 PT and APTT tests/hour Coagpia AT Reagent Similarities Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Intended use Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. HemoslL Liquid Antithrombin is an automated chromogenic assay for the quantitative determination of Antithrombin in human citrated plasma as an aid in the diagnosis of hereditary and acquired Antithrombin deficiency and to monitor Antithrombin substitution therapy. This in vitro diagnostic test is based on a synthetic chromogenic substrate and on Factor Xa inactivation. As a consequence, it is specific and not influenced by Heparin Cofactor II. Antithrombin levels in patient plasma are measured automatically on IL Coagulation Systems. Analyte Antithrombin Same Reagent State Liquid, ready to use Same Method Chromogenic Same Detection Photometric Same 6 Differences Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Key Components · Factor Xa (bovine) · Heparin N-Acetyl-D-arginyl-glycyl-L- arginyl- p-nitroanilide dihydrochloride (chromogenic substrate) · Factor Xa (bovine) · Heparin N-α-Z-D-Arg-Gly-Arg- pNA·2HCl (chromogenic substrate) Sample Type Human citrated plasma Human citrated plasma Expected Values 89–131% 83−128% Repeatability 0.7–2.9% 2.2–7.4% Within Laboratory Precision 1.1–5.8% 3.1–8.6% Linearity 14–140% 10–150% Clinical reportable range 14–150% 10–150% Coagpia Calibrator Similarities Item Device Coagpia Calibrator Predicate HemosIL Calibration Plasma Intended use Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent HemosIL Calibration plasma is intended Classification:

idK173202_s0_e2000

K173202.txt

panel

Hematology (81)

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K173202 B. Purpose for Submission: New device C. Measurand: Antithrombin activity (%) D. Type of Test: Quantitative chromogenic test E. Applicant: Sekisui Medical Co., LTD F. Proprietary and Established Names: CP3000 Coagulation Analyzer Coagpia AT Reagent Coagpia Calibrator Coagpia Control Set G. Regulatory Information: 1. Regulation section: Device Regulation Section CP3000 Coagulation Analyzer 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagpia AT Reagent 21 CFR 864.7060, Antithrombin III Assay Coagpia Calibrator 21 CFR 862.1150 Calibrator Coagpia Control Set 21 CFR 864.5425, Plasma, coagulation control 2. Classification: Class II 2 3. Product code: Device Product Code CP3000 Coagulation Analyzer JPA Coagpia AT Reagent JBQ Coagpia Calibrator JIX Coagpia Control Set GGN 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): CP3000 Coagulation Analyzer The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. Coagpia Calibrator The Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent Coagpia Control Set The Coagpia Control set contains 2 levels of assayed plasma intended for the quality control of the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel. For in vitro diagnostic use. · Coagpia AT Reagent 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: CP3000 Coagulation Analyzer I. Device Description: CP3000 Coagulation Analyzer The CP3000 is an automated blood coagulation instrument which performs tests for specific parameters in citrated human plasma. The CP3000 system is capable of performing chromogenic assays, which allows analysis for both direct hemostasis measurements and calculated parameters. For this assay methodology, the analyzer employs two photometric detection methods: light scattering and absorbance. The light scattering method uses light emitting diodes at a wavelength of 660 nm, and the absorbance method uses a halogen lamp with filters providing wavelengths at 405, 570, and 730 nm. The analyzer components include the analyzer hardware and its controlling software (firmware), a personal computer (PC) with its user interface, result calculations, and patient data management software. The PC also provides the software to communicate with the host Laboratory Information System (LIS). Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human plasma on the CP3000 analyzer. R1 contains bovine Factor Xa, heparin sodium salt (porcine), buffer, surfactant and preservative. R2 contains a protease substrate N- acetyl-D-arginyl-glycyl-L-arginyl-p-nitroanilide, buffer, surfactant and preservative. Both reagents are liquid and do not require any preparation prior to use. Coagpia Calibrator The Coagpia Calibrator is lyophilized human plasma and is suitable for the calibration of the antithrombin activity assay using Coagpia AT Reagent on the CP3000 coagulation analyzer. Coagpia Control Set The Coagpia Control Set is lyophilized human plasma supplied as two levels (Level 1 Control and Level 2 Control) and is suitable for use with the antithrombin activity assay using Coagpia AT Reagent on the CP3000 analyzer. J. Substantial Equivalence Information: 1. Predicate device name(s) and 510(k) numbers: Predicate Device Predicate 510(k) Number ACL TOP 700 LAS K160276 HemosIL Liquid Antithrombin K062431 HemosIL Calibration Plasma K041905 HemosIL Normal Control Assayed K021023 4 Predicate Device Predicate 510(k) Number HemosIL Low Abnormal Control Assayed K021024 2. Comparison with predicate: CP3000 Coagulation Analyzer Similarities Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Intended use The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. The ACL TOP is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The system provides results for both direct hemostasis measurement and calculated parameters. Interface · Touch screen operation Windows 7 Operating System Same Options Available with closed tube sampling (CTS) function Same Analytes Multiple Same Reagent Handling · Refrigerated on board · Internal bar code sample identification Same Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Application type · Chromogenic · Coagulometric (turbidimetric) · Measurement Chromogenic (absorbance) measurement · Immunological measurement 5 Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Detection Photometric · Absorbance · Light scattering Photometric · Absorbance Wavelengths · 405 nm · 570 nm · 660 nm · 730 nm · 405 nm · 671 nm Throughput (non- CTS) Up to 400 clotting tests/hour Up to 330 PT and APTT tests/hour Coagpia AT Reagent Similarities Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Intended use Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. HemoslL Liquid Antithrombin is an automated chromogenic assay for the quantitative determination of Antithrombin in human citrated plasma as an aid in the diagnosis of hereditary and acquired Antithrombin deficiency and to monitor Antithrombin substitution therapy. This in vitro diagnostic test is based on a synthetic chromogenic substrate and on Factor Xa inactivation. As a consequence, it is specific and not influenced by Heparin Cofactor II. Antithrombin levels in patient plasma are measured automatically on IL Coagulation Systems. Analyte Antithrombin Same Reagent State Liquid, ready to use Same Method Chromogenic Same Detection Photometric Same 6 Differences Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Key Components · Factor Xa (bovine) · Heparin N-Acetyl-D-arginyl-glycyl-L- arginyl- p-nitroanilide dihydrochloride (chromogenic substrate) · Factor Xa (bovine) · Heparin N-α-Z-D-Arg-Gly-Arg- pNA·2HCl (chromogenic substrate) Sample Type Human citrated plasma Human citrated plasma Expected Values 89–131% 83−128% Repeatability 0.7–2.9% 2.2–7.4% Within Laboratory Precision 1.1–5.8% 3.1–8.6% Linearity 14–140% 10–150% Clinical reportable range 14–150% 10–150% Coagpia Calibrator Similarities Item Device Coagpia Calibrator Predicate HemosIL Calibration Plasma Intended use Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent HemosIL Calibration plasma is intended Panel:

idK173202_s0_e2000

K173202.txt

applicant

Sekisui Medical Co., LTD

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM A. 510(k) Number: K173202 B. Purpose for Submission: New device C. Measurand: Antithrombin activity (%) D. Type of Test: Quantitative chromogenic test E. Applicant: Sekisui Medical Co., LTD F. Proprietary and Established Names: CP3000 Coagulation Analyzer Coagpia AT Reagent Coagpia Calibrator Coagpia Control Set G. Regulatory Information: 1. Regulation section: Device Regulation Section CP3000 Coagulation Analyzer 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies Coagpia AT Reagent 21 CFR 864.7060, Antithrombin III Assay Coagpia Calibrator 21 CFR 862.1150 Calibrator Coagpia Control Set 21 CFR 864.5425, Plasma, coagulation control 2. Classification: Class II 2 3. Product code: Device Product Code CP3000 Coagulation Analyzer JPA Coagpia AT Reagent JBQ Coagpia Calibrator JIX Coagpia Control Set GGN 4. Panel: Hematology (81) H. Intended Use: 1. Intended use(s): CP3000 Coagulation Analyzer The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. Coagpia Calibrator The Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent Coagpia Control Set The Coagpia Control set contains 2 levels of assayed plasma intended for the quality control of the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel. For in vitro diagnostic use. · Coagpia AT Reagent 2. Indication(s) for use: Same as Intended Use(s) above 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: CP3000 Coagulation Analyzer I. Device Description: CP3000 Coagulation Analyzer The CP3000 is an automated blood coagulation instrument which performs tests for specific parameters in citrated human plasma. The CP3000 system is capable of performing chromogenic assays, which allows analysis for both direct hemostasis measurements and calculated parameters. For this assay methodology, the analyzer employs two photometric detection methods: light scattering and absorbance. The light scattering method uses light emitting diodes at a wavelength of 660 nm, and the absorbance method uses a halogen lamp with filters providing wavelengths at 405, 570, and 730 nm. The analyzer components include the analyzer hardware and its controlling software (firmware), a personal computer (PC) with its user interface, result calculations, and patient data management software. The PC also provides the software to communicate with the host Laboratory Information System (LIS). Coagpia AT Reagent Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human plasma on the CP3000 analyzer. R1 contains bovine Factor Xa, heparin sodium salt (porcine), buffer, surfactant and preservative. R2 contains a protease substrate N- acetyl-D-arginyl-glycyl-L-arginyl-p-nitroanilide, buffer, surfactant and preservative. Both reagents are liquid and do not require any preparation prior to use. Coagpia Calibrator The Coagpia Calibrator is lyophilized human plasma and is suitable for the calibration of the antithrombin activity assay using Coagpia AT Reagent on the CP3000 coagulation analyzer. Coagpia Control Set The Coagpia Control Set is lyophilized human plasma supplied as two levels (Level 1 Control and Level 2 Control) and is suitable for use with the antithrombin activity assay using Coagpia AT Reagent on the CP3000 analyzer. J. Substantial Equivalence Information: 1. Predicate device name(s) and 510(k) numbers: Predicate Device Predicate 510(k) Number ACL TOP 700 LAS K160276 HemosIL Liquid Antithrombin K062431 HemosIL Calibration Plasma K041905 HemosIL Normal Control Assayed K021023 4 Predicate Device Predicate 510(k) Number HemosIL Low Abnormal Control Assayed K021024 2. Comparison with predicate: CP3000 Coagulation Analyzer Similarities Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Intended use The CP3000 is a fully automated, random-access in vitro blood coagulation analyzer intended for use by healthcare professionals in the clinical laboratory. The CP3000 analyzer is designed to process plasma samples photometrically using chromogenic assays. The ACL TOP is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic clinical use in the hemostasis laboratory for coagulation and/or fibrinolysis testing in the assessment of thrombosis and/or hemostasis. The system provides results for both direct hemostasis measurement and calculated parameters. Interface · Touch screen operation Windows 7 Operating System Same Options Available with closed tube sampling (CTS) function Same Analytes Multiple Same Reagent Handling · Refrigerated on board · Internal bar code sample identification Same Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Application type · Chromogenic · Coagulometric (turbidimetric) · Measurement Chromogenic (absorbance) measurement · Immunological measurement 5 Differences Item Device CP3000 (CTS and non-CTS) Predicate ACL TOP 700 (CTS and non-CTS) Detection Photometric · Absorbance · Light scattering Photometric · Absorbance Wavelengths · 405 nm · 570 nm · 660 nm · 730 nm · 405 nm · 671 nm Throughput (non- CTS) Up to 400 clotting tests/hour Up to 330 PT and APTT tests/hour Coagpia AT Reagent Similarities Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Intended use Coagpia AT Reagent is intended for the quantitative determination of antithrombin (AT) activity in human 3.2% citrated venous plasma. The reagent is intended for use on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. HemoslL Liquid Antithrombin is an automated chromogenic assay for the quantitative determination of Antithrombin in human citrated plasma as an aid in the diagnosis of hereditary and acquired Antithrombin deficiency and to monitor Antithrombin substitution therapy. This in vitro diagnostic test is based on a synthetic chromogenic substrate and on Factor Xa inactivation. As a consequence, it is specific and not influenced by Heparin Cofactor II. Antithrombin levels in patient plasma are measured automatically on IL Coagulation Systems. Analyte Antithrombin Same Reagent State Liquid, ready to use Same Method Chromogenic Same Detection Photometric Same 6 Differences Item Device Coagpia AT Reagent Predicate HemosIL Liquid Antithrombin Key Components · Factor Xa (bovine) · Heparin N-Acetyl-D-arginyl-glycyl-L- arginyl- p-nitroanilide dihydrochloride (chromogenic substrate) · Factor Xa (bovine) · Heparin N-α-Z-D-Arg-Gly-Arg- pNA·2HCl (chromogenic substrate) Sample Type Human citrated plasma Human citrated plasma Expected Values 89–131% 83−128% Repeatability 0.7–2.9% 2.2–7.4% Within Laboratory Precision 1.1–5.8% 3.1–8.6% Linearity 14–140% 10–150% Clinical reportable range 14–150% 10–150% Coagpia Calibrator Similarities Item Device Coagpia Calibrator Predicate HemosIL Calibration Plasma Intended use Coagpia Calibrator is intended for use as a calibration plasma for the following Sekisui coagulation assay on Sekisui CP3000 analyzers by trained laboratory personnel in clinical laboratories. For in vitro diagnostic use. · Coagpia AT Reagent HemosIL Calibration plasma is intended Applicant:

idK173202_s6000_e8000

K173202.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

idate and predicate). Patient sample demographics included 218 females, aged from neonate to 95 years old, and 186 males, aged from neonate to 83 years old. Of the 482 samples, 92 samples were pediatric samples. Deming (orthogonal) regression and ordinary linear regression (OLR) were used to determine Pearson’s correlation coefficient (r), slope and intercept along with their 95% CIs were provided. Bias was determined based on the Deming regression model. The calculated bias along with its 95% CI were reported for the lower quartile, upper quartile and medical decision points (MDP). All results were within the pre-defined acceptance criteria. 14 Regression Sample range N Slope (95% CI) Intercept (95% CI) R Deming 20–140% 482 1.012 (1.000, 1.024) 0.4 (-0.8, 1.5) 0.9909 OLR 20–140% 482 1.002 (0.990, 1.015) 1.2 (0.0, 2.3) 0.9909 Bias Summary for all samples (N=482) Level Predicted Recovery (95% Cl) Bias (95% Cl) Midpoint, lower quartile 46 46.9 (46.2, 47.6) 2.0% (0.4, 3.5) MDP 70 71.2 (70.7, 71.6) 1.7% (1.0, 2.3) MDP 89 90.4 (90.0, 90.8) 1.6% (1.1, 2.0) Midpoint, upper quartile 133 134.9 (134.3, 135.6) 1.4% (1.0, 2.0) b. Equivalence Studies Matrix comparison: A matrix comparison study was conducted to demonstrate equivalence between fresh and frozen citrated plasma samples. The study was conducted in one clinical site, using one CP3000 analyzer, three reagent lots and one calibrator lot. Sixty fresh samples covering the reportable range were measured on the CP3000 analyzer within 4 hours after blood collection. The frozen time points included 2 and 3 weeks of storage with up to two freeze/thaw cycles at -20°C and 4 months of storage with up to four freeze/thaw cycles at -80°C. Results were analyzed using Passing-Bablok regression, Pearson correlation coefficient and Bland-Altman plots. The study results demonstrated comparability between fresh and frozen samples and met the pre- defined acceptance criteria for all applicatons. Open tube vs. Closed tube sampling (CTS) mode The purpose and scope of this study was to demonstrate the equivalence of the testing results obtained from capped and uncapped blood collection tubes using CP3000 with CTS mode. The assay was performed first on the capped tube then on the same tube, uncapped. Sixty-four plasma samples covering the reportable range of the AT assay on the CP3000 analyzer were used to conduct this study. Three CP3000 instruments were used in this study. The results from the three CP3000 analyzers were compared. The study results demonstrated comparability between the data sets. Closed tube sampling (CTS) instrument vs. Non-CTS The purpose and scope of this study was to demonstrate the equivalence of the test 15 results obtained using CP3000 instrument models CTS versus Non-CTS. One hundred and twenty frozen plasma samples covering the reportable range of the AT assay was used to conduct the study. Each sample was aliquoted into six sample cups. The samples were measured in singlicate on CP3000 instruments (three CP3000 with CTS and three CP3000 without CTS) over three days. The performance between the two CP3000 analyzer models, CP3000 analyzer with the option of CTS capability and CP3000 analyzer without CTS capability was determined to be equivalent. 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Reference range: Adult reference range The reference interval studies were conducted at three clinical sites in the U.S. at different geographic locations to reflect the U.S. population. Citrated plasma samples were obtained from 179 apparently healthy individuals ≥ 21 years with no current or recent history of a bleeding disorder or unexpected extended bleeding episodes. Results from all sites were pooled and all reference intervals were established by calculating the non-parametric 95% confidence interval (2.5th to 97.5th percentiles). The calculated normal reference range for the Coagpia AT assay is 89% to 131%. Pediatric reference range: The pediatric reference range was calculated based on the data provided in the method comparison study. These values were supported by peer reviewed literature1. 1 Toulon et. al., Age dependency of coagulation parameters in pediatric populations, Thrombosis and Haemostasis 116 (1): 9-16, 2016 16 Range 15 days to 4 weeks 1 to 5 months 6 to 11 months 1 to 5 years 6 to 10 years 11 to 17 years Calculated Coagpia AT 33–63% 29–121% 63–122% 61–129% 64–137% 69–137% N. Instrument Name: CP3000 Coagulation Analyzer O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes _____X___ or No ________ 3. Specimen Identification: Manual entry and barcode reader 4. Specimen Sampling and Handling: Instrument available with and without cap piercing capabalities. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 17 R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK173202_s6000_e8000

K173202.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

(candidate and predicate). Patient sample demographics included 218 females, aged from neonate to 95 years old, and 186 males, aged from neonate to 83 years old. Of the 482 samples, 92 samples were pediatric samples. Deming (orthogonal) regression and ordinary linear regression (OLR) were used to determine Pearson’s correlation coefficient (r), slope and intercept along with their 95% CIs were provided. Bias was determined based on the Deming regression model. The calculated bias along with its 95% CI were reported for the lower quartile, upper quartile and medical decision points (MDP). All results were within the pre-defined acceptance criteria. 14 Regression Sample range N Slope (95% CI) Intercept (95% CI) R Deming 20–140% 482 1.012 (1.000, 1.024) 0.4 (-0.8, 1.5) 0.9909 OLR 20–140% 482 1.002 (0.990, 1.015) 1.2 (0.0, 2.3) 0.9909 Bias Summary for all samples (N=482) Level Predicted Recovery (95% Cl) Bias (95% Cl) Midpoint, lower quartile 46 46.9 (46.2, 47.6) 2.0% (0.4, 3.5) MDP 70 71.2 (70.7, 71.6) 1.7% (1.0, 2.3) MDP 89 90.4 (90.0, 90.8) 1.6% (1.1, 2.0) Midpoint, upper quartile 133 134.9 (134.3, 135.6) 1.4% (1.0, 2.0) b. Equivalence Studies Matrix comparison: A matrix comparison study was conducted to demonstrate equivalence between fresh and frozen citrated plasma samples. The study was conducted in one clinical site, using one CP3000 analyzer, three reagent lots and one calibrator lot. Sixty fresh samples covering the reportable range were measured on the CP3000 analyzer within 4 hours after blood collection. The frozen time points included 2 and 3 weeks of storage with up to two freeze/thaw cycles at -20°C and 4 months of storage with up to four freeze/thaw cycles at -80°C. Results were analyzed using Passing-Bablok regression, Pearson correlation coefficient and Bland-Altman plots. The study results demonstrated comparability between fresh and frozen samples and met the pre- defined acceptance criteria for all applicatons. Open tube vs. Closed tube sampling (CTS) mode The purpose and scope of this study was to demonstrate the equivalence of the testing results obtained from capped and uncapped blood collection tubes using CP3000 with CTS mode. The assay was performed first on the capped tube then on the same tube, uncapped. Sixty-four plasma samples covering the reportable range of the AT assay on the CP3000 analyzer were used to conduct this study. Three CP3000 instruments were used in this study. The results from the three CP3000 analyzers were compared. The study results demonstrated comparability between the data sets. Closed tube sampling (CTS) instrument vs. Non-CTS The purpose and scope of this study was to demonstrate the equivalence of the test 15 results obtained using CP3000 instrument models CTS versus Non-CTS. One hundred and twenty frozen plasma samples covering the reportable range of the AT assay was used to conduct the study. Each sample was aliquoted into six sample cups. The samples were measured in singlicate on CP3000 instruments (three CP3000 with CTS and three CP3000 without CTS) over three days. The performance between the two CP3000 analyzer models, CP3000 analyzer with the option of CTS capability and CP3000 analyzer without CTS capability was determined to be equivalent. 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Reference range: Adult reference range The reference interval studies were conducted at three clinical sites in the U.S. at different geographic locations to reflect the U.S. population. Citrated plasma samples were obtained from 179 apparently healthy individuals ≥ 21 years with no current or recent history of a bleeding disorder or unexpected extended bleeding episodes. Results from all sites were pooled and all reference intervals were established by calculating the non-parametric 95% confidence interval (2.5th to 97.5th percentiles). The calculated normal reference range for the Coagpia AT assay is 89% to 131%. Pediatric reference range: The pediatric reference range was calculated based on the data provided in the method comparison study. These values were supported by peer reviewed literature1. 1 Toulon et. al., Age dependency of coagulation parameters in pediatric populations, Thrombosis and Haemostasis 116 (1): 9-16, 2016 16 Range 15 days to 4 weeks 1 to 5 months 6 to 11 months 1 to 5 years 6 to 10 years 11 to 17 years Calculated Coagpia AT 33–63% 29–121% 63–122% 61–129% 64–137% 69–137% N. Instrument Name: CP3000 Coagulation Analyzer O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ___X_____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes _____X___ or No ________ 3. Specimen Identification: Manual entry and barcode reader 4. Specimen Sampling and Handling: Instrument available with and without cap piercing capabalities. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 17 R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK182357_s0_e2000

K182357.txt

purpose for submission

To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Purpose for submission:

idK182357_s0_e2000

K182357.txt

measurand

Eravacycline 20µg

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Measurand:

idK182357_s0_e2000

K182357.txt

type of test

Antimicrobial Susceptibility Test Disks

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Type of test:

idK182357_s0_e2000

K182357.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Classification:

idK182357_s0_e2000

K182357.txt

product code

JTN

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Product code:

idK182357_s0_e2000

K182357.txt

panel

83, Microbiology

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Panel:

idK182357_s0_e2000

K182357.txt

intended use

HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Intended use:

idK182357_s0_e2000

K182357.txt

predicate device name

HardyDisk Tigecycline 15µg

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Predicate device name:

idK182357_s0_e2000

K182357.txt

applicant

Hardy Diagnostics

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Applicant:

idK182357_s0_e2000

K182357.txt

proprietary and established names

HardyDisk AST Eravacycline 20µg (ERV20)

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Proprietary and established names:

idK182357_s0_e2000

K182357.txt

regulation section

21 CFR 866.1620 Antimicrobial Susceptibility Test Disc

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: K182357 B. Purpose for Submission: To obtain a susbstantial equivalence determination for Eravacycline Antimicrobial Susceptibility Test Disk C. Measurand: Eravacycline 20µg D. Type of Test: Antimicrobial Susceptibility Test Disks E. Applicant: Hardy Diagnostics F. Proprietary and Established Names: HardyDisk AST Eravacycline 20µg (ERV20) G. Regulatory Information: 1. Regulation section: 21 CFR 866.1620 Antimicrobial Susceptibility Test Disc 2. Classification: Class II 3. Product code: JTN 4. Panel: 83, Microbiology 2 H. Intended Use: 1. Intended use(s): HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 2. Indication(s) for use: Use of HardyDisk AST Eravacycline 20µg (ERV20) for in vitro agar diffusion susceptibility testing is indicated when there is need to determine the susceptibility of bacteria amoung the Enterobacteriaceae to Eravacyline. HardyDisk AST Eravacycline at concentration 20µg can be used to determine the zone diameter (mm) of Eravacycline against the following bacteria among the Enterobacteriaceae. Eravacycline has been shown to be active both clinically and in vitro against the following organisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Among the Enterobacteriaceae, Eravacycline has been shown to be active in vitro against most of the following bacteria, but their clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes HardyDisk AST Disks are used for semi-quantitative in vitro susceptibility testing by the agar diffusion test procedure (Kirby-Bauer) of rapidly growing and certain fastidious bacterial pathogens. Standardized methods for agar diffusion testing have been described for Enterobacteriaceae, Staphylococcus spp., Pseudomonas spp., Acinetobacter spp., Listeria monocytogenes, Enterococcus spp., and by modified procedures, Haemophilus spp., Neisseria gonorrhoeae, N. meningitidis and Streptococcus spp., including Streptococcus pneumoniae. 3. Special conditions for use statement(s): For prescription use only 3 4. Special instrument requirements: Not applicable. I. Device Description: HardyDisk AST Disks utilize 6-mm diameter white filter paper disks. The disks are prepared by impregnating absorbent paper with a known concentration of 20µg Eravacycline. The disks are marked with the code ERV20, on both sides. HardyDisk AST Disks are supplied in plastic cartridges containing 50 disks each. They are also packaged as one cartridge per vial with desiccant or five cartridges per vial with desiccant. J. Substantial Equivalence Information: 1. Predicate device name(s): HardyDisk Tigecycline 15µg 2. Predicate 510(k) number(s): K062245 3. Comparison with predicate: Table 1: Comparison with the Predicate Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg Test Method Antimicrobial Susceptibility Testing using paper disks impregnated with an antimicrobial agent Same Methodology Kirby-Bauer Disk Diffusion Susceptibility Test Protocol requires the user to determine categorical interpretations (S/I/R) using the measured zone diameters. Same Inoculum Prepared from pure isolated colonies to match the turbidity equivalent of a 0.5 McFarland in Tryptic Soy Broth. Same Inoculation Method Dip a sterile swab into the prepared inoculum and streak an appropriate agar plate’s surface three times. Add Same 4 Similarities Item Device K182357 HardyDisk Eravacycline 20µg Predicate K062245 HardyDisk Tigecycline 15µg the disks impregnated with the antimicrobial agent to the surface of the plate. Incubate the agar plate agar side up in a 35 ± 2°C incubator for 16- 18 hours. Reading Method The user will interpret the zone diameters according established interpretive criteria for the drug. Same Differences Item Device Predicate Product Name HardyDisk Eravacycline 20µg (ERV20) HardyDisk Tigecycline Antimicrobial Agent Eravacycline Tigecycline Concentration 20µg 15µg K. Standard/Guidance Document Referenced (if applicable): CLSI M100 28th Edition, Performance Standards for Antimicrobial Susceptibility Testing L. Test Principle: The HardyDisk AST Disk is based on the agar diffusion (Kirby-Bauer) methodology. It utilizes dried filter paper disks impregnated with a known concentration of an antimicrobial agent that are placed onto the test medium surface. Mueller Hinton agar is recommended for agar diffusion testing of non-fastidious organisms and Mueller Hinton with 5% Sheep Blood is recommended for Streptococcus spp. Three to five similar colonies are transferred to 4-5 mL of a suitable broth medium. The broth is incubated at 35°C for 2-6 hours to develop a turbidity that exceeds or is equivalent to a 0.5 McFarland standard. Alternatively, a direct broth or saline suspension of colonies may be prepared from an overnight culture. The final inoculum density should be equivalent to a 0.5 McFarland turbidity standard. The inoculum density may also be standardized photometrically. Within 15 minutes of inoculum preparation, the Mueller Hinton agar plate is streaked with an inoculated swab to obtain an even inoculation of organism. Disks are aseptically placed onto the agar surface with a disk dispenser and the disks are pressed down with a sterile needle or forceps to make contact with the agar surface. Agar plates are incubated in an ambient air incubator at 35±2°C for 16 - 18 hours. Fastidious organisms are tested using appropriate media incubated in an atmosphere enriched with 5% CO2, as recommended in the CLSI M02 approved standard document. 5 After incubation the agar medium is examined for a zone of inhibition around the disks. The zones of inhibition are measured to the nearest millimeter and compared to recognized zone size ranges for the antimicrobial agent being tested. M. Performance Characteristics (if/when applicable): Descriptive characteristics were sufficient for the HardyDisk Eravacycline 20µg (ERV20) disk based on extensive data from several microbiology disk studies evaluated by CDER which were used to generate the breakpoints and quality control (QC) expected ranges used for this subject device. The disk data used to support this submission included data from testing Enterobacteriaceae within the spectrum of activity of Eravacycline. Data was obtained from reproducibility, quality control and disk to MIC correlation studies and was generated in accordance with the CDER Clinical/Antimicrobial guidance, Microbiology Data for Systemic Antibacterial Drugs- Development, Analysis, and Presentation to ensure precise, accurate, and reproducible results. For this review, the interpretative criteria are applied broadly to include the Enterobacteriaceae family according to the FDA STIC website. Testing has been expanded to include members of the family and is not limited only to the indicated species. The following statements are added as footnotes to the Eravacycline 20µg interpretative criteria table for Enterobacteriaceae in the HardyDisk AST package insert: o The safety and efficacy of Eravacycline in treating clinical infections due to organisms other than Citrobacter freundii,Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Klebsiella pneumoniae, may or may not have been established in adequate and well-controlled clinical trials. The clinical significance of susceptibility information in such instances is unknown. o The current absence of resistant isolates precludes defining any results other than “Susceptible”. Isolates yielding results other than “Susceptible” should be submitted to a reference laboratory for further testing. o Activity of eravacycline was demonstrated Regulation section:

idK182357_s2000_e4000

K182357.txt

proposed labeling

The labeling supports the finding of substantial equivalence for this device.

acteriaceae in the presence of certain beta-lactamases, including extended spectrum beta- lactamases, and AmpC. However, some beta-lactamase-producing isolates may confer resistance to eravacycline via other resistance mechanisms. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 7 5. Expected values/Reference range: The Eravacycline interpretative criteria for disk diffusion is shown in Table 2 below. Table 2: Interpretative Criteria for Eravacycline Disk Diffusiona (Zone diameter in mm) Organism(s) Interpretative Criteria Enterobacteriaceae Susceptible ≥15 a FDA-recognized Antimicrobial Susceptibility Test Interpretive Criteria Website https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm5 75163.htm. The QC strains and expected ranges are the same as recommended in CLSI M100 28th edition. N. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK182357_s2000_e4000

K182357.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

Enterobacteriaceae in the presence of certain beta-lactamases, including extended spectrum beta- lactamases, and AmpC. However, some beta-lactamase-producing isolates may confer resistance to eravacycline via other resistance mechanisms. 1. Analytical performance: a. Precision/Reproducibility: Not applicable b. Linearity/assay reportable range: 6 Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Not applicable d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 7 5. Expected values/Reference range: The Eravacycline interpretative criteria for disk diffusion is shown in Table 2 below. Table 2: Interpretative Criteria for Eravacycline Disk Diffusiona (Zone diameter in mm) Organism(s) Interpretative Criteria Enterobacteriaceae Susceptible ≥15 a FDA-recognized Antimicrobial Susceptibility Test Interpretive Criteria Website https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm5 75163.htm. The QC strains and expected ranges are the same as recommended in CLSI M100 28th edition. N. Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK171770_s0_e2000

K171770.txt

purpose for submission

To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Purpose for submission:

idK171770_s0_e2000

K171770.txt

measurand

tcdB gene of toxigenic Clostridium difficile

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Measurand:

idK171770_s0_e2000

K171770.txt

type of test

Real-time PCR assay

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Type of test:

idK171770_s0_e2000

K171770.txt

classification

II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Classification:

idK171770_s0_e2000

K171770.txt

product code

OZN, OOI

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Product code:

idK171770_s0_e2000

K171770.txt

panel

Microbiology (83)

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Panel:

idK171770_s0_e2000

K171770.txt

intended use

The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Intended use:

idK171770_s0_e2000

K171770.txt

predicate device name

cobas Cdiff Test for use on the cobas 4800 System

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Predicate device name:

idK171770_s0_e2000

K171770.txt

applicant

Roche Molecular Systems, Inc.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Applicant:

idK171770_s0_e2000

K171770.txt

proprietary and established names

cobas Cdiff Nucleic acid test for use on the cobas Liat System

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Proprietary and established names:

idK171770_s0_e2000

K171770.txt

regulation section

21 CFR 866.3130, Clostridium difficile toxin gene amplification assay

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: K171770 B. Purpose for Submission: To obtain a substantial equivalence determination for the cobas Cdiff Nucleic acid test for use on the cobas Liat System C. Measurand: tcdB gene of toxigenic Clostridium difficile D. Type of Test: Real-time PCR assay E. Applicant: Roche Molecular Systems, Inc. F. Proprietary and Established Names: cobas Cdiff Nucleic acid test for use on the cobas Liat System G. Regulatory Information: 1. Regulation section: 21 CFR 866.3130, Clostridium difficile toxin gene amplification assay 2. Classification: II 3. Product code: OZN, OOI 2 4. Panel: Microbiology (83) H. Intended Use: 1. Intended use(s): The cobas Cdiff Nucleic acid test for use on the cobas Liat System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas Cdiff Nucleic acid test for use on the cobas Liat System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): For prescription use only The assay has only been validated for use with unformed or partially formed stool specimens that have been transferred into the cobas PCR Media tube according to the Instructions For Use. 4. Special instrument requirements: cobas Liat Analyzer I. Device Description: The cobas Cdiff Nucleic acid test for use on the cobas Liat System (cobas Liat Cdiff) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas Liat System is for in vitro diagnostic use. The system is designed to identify the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real- time detection, and result interpretation. Reagents and controls: · cobas Cdiff Assay Tube · cobas Cdiff Positive and Negative Control Kit for use on the cobas Liat System 3 Additional materials required but not provided: · cobas PCR Media Uni Swab Sample Kit J. Substantial Equivalence Information: 1. Predicate device name(s): cobas Cdiff Test for use on the cobas 4800 System 2. Predicate 510(k) number(s): K142422 3. Comparison with predicate: Similarities Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Sample type Unformed soft stool specimens Same Amplification Technology Real-time PCR Same Detection Technology TaqMan probes with fluorescent dyes Same Assay target C. difficile Toxin B gene (tcdB) Same Sample extraction Automated magnetic bead- based nucleic acid extraction Same Differences Item Device cobas Cdiff Nucleic acid test for use on the cobas Liat System Predicate cobas Cdiff Test for use on the cobas 4800 System (K142422) Instrument platform cobas Liat system cobas 4800 system Samples/controls per run One sample per run Up to 24 or 96 samples per run Test duration Results within ~20 minutes after specimen loading Results within 2.5 hours after specimen loading Internal control design A whole organism, gram- positive bacterial control (chemically inactivated Bacillus thuringiensis israelensis) Lambda phage with encapsulated internal control sequence 4 K. Standard/Guidance Document Referenced (if applicable): Not applicable L. Test Principle: The cobas Liat Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas Liat Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas Cdiff assay tube, no reagent preparation or additional steps are required. The cobas Liat System consists of a cobas Liat Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas Liat Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas Cdiff assay tube, thereby eliminating the potential for cross- contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas Liat Analyzer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Reproducibility The reproducibility of the cobas Liat Cdiff test was established in a multi-site investigation (two external sites and one internal site) using simulated clinical samples evaluated across reagent lot, site, operator, and testing day. Overall, 818 tests were performed in this study, out of which 798 were valid for the study. Only those valid results were included in the final percent agreement analysis. Panels consisted of three members: one negative specimen and two specimens with 5 different concentrations of one strain of toxigenic C. difficile: a low positive concentration near the limit of detection (~1X LOD), and a moderate positive concentration (~3X LOD). A run was defined as testing of three replicates of a panel member. For each of three lots, panels were run on five different nonconsecutive days by two different operators at each of the three sites. Table 1 shows the percent agreement to expected results by panel member. Results were in agreement when a positive panel member had a valid result of Positive (Cdiff Detected) for the analyte or when the negative panel member had a valid result of Negative (Cdiff Not Detected) for the analyte. For the ~1X LOD panel members, the overall percent agreement was 98.5% with a lower bound of the two-sided 95% Score CI of 96.2%. Overall percent agreement was 99.3% for the ~3X LOD panel member and 100% for the negative panel member. Table 1. Reproducibility - Qualitative Results Panel Member Number of Valid Test Results Percent Agreement with Expected Result (95% CI) Met Acceptance Criteria Negative 262 100.0% (262/262) (98.6%, 100.0%) n/a ~1xLOD 266 98.5% (262/266) (96.2%, 99.4%) Yes ~3xLOD 270 99.3% (268/270) (97.3%, 99.8%) n/a Table 2 below presents the overall standard deviation (SD) and percent coefficient of variation (% CV) of cycle threshold (Ct) values for positive panel members at ~1X LOD and ~3X LOD concentrations, as well as the variance attributed to individual components (lot, site, operator, testing day, and within-run). Within-run variation refers to the variation within a ‘study run’ that consists of the three replicates for a given panel member processed by the same operator on the same analyzer on the same day. Across all components, the total % CV was ≤ 1.9% with respect to the Ct value for all positive panel members. Within each component, the % CV was ≤ 1.6% across positive panel members. Table 2. Reproducibility - Ct Value Results Lot Site Operator Day Within- Run Total Panel Member N Mean Ct SD CV SD CV SD CV SD CV SD CV SD CV ~1xLOD 262 31.4 0.13 0.4% 0.26 0.8% 0.00 0.0% 0.13 0. Regulation section:

idK171770_s6000_e8000

K171770.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

remnant specimens were prospectively collected from symptomatic patients suspected of CDI. Of these, 172 were excluded according to the criteria for enrollment, storage, or cobas Liat Cdiff test processing as defined in the protocol. Of the 1,016 specimens tested with the cobas Liat Cdiff test, 1.4% 13 (14/1016) were initially invalid and 0.2% (2/1016) initially had failed results. After one retest per invalid or failed result following the labeled instructions, the final invalid rate was 0.1% (1/1016) and the final failed rate was 0% (0/1016). The three repeat invalid test results were excluded from the final performance analysis. A total of 1,013 evaluable specimens were included in the study from 483 males (47.7%) and 530 females (52.3%) with a median age of 59 years (range 5 to 98). All 1,013 specimens had valid results for both combined direct and enrichment culture and the cobas Liat Cdiff test. Of the 1,013 specimens, 179 were positive for toxigenic C. difficile using the combined results from direct and enrichment toxigenic culture, for a prevalence of 17.7% for the study. Comparison with Combined Direct and Broth Enrichment Culture The clinical performance of the cobas Liat Cdiff test compared with the combined results of direct and enrichment toxigenic culture are shown in Table 9. The sensitivity and specificity of the cobas Liat Cdiff test were 87.2% (156/179; 95% CI: 81.5% to 91.3%) and 98.1% (818/834; 95% CI: 96.9% to 98.8%), respectively; and the PPV and NPV were 90.7% (95% CI: 85.4% to 94.2%) and 97.3% (95% CI: 95.9% to 98.2%), respectively. Of the 23 specimens with false-negative cobas Liat Cdiff test results relative to combined direct culture and enrichment culture, 19 were negative, three were positive and one was invalid by an FDA-cleared NAAT for tcdB DNA. Of the 16 specimens with false-positive cobas Liat Cdiff test results relative to combined direct and enrichment culture, 14 were positive and two were negative by the FDA-cleared NAAT. Table 9. Comparison with Combined Direct and Enriched Culture Combined Direct and Enrichment Culture Result Positive Negative Total cobas Liat Cdiff Test Result Detected 156 16a 172 Not Detected 23b 818 841 Total 179 834 1013 95% CI Sensitivity 87.2% (156/179) 81.5% to 91.3% Specificity 98.1% (818/834) 96.9% to 98.8% PPV 90.7% (156/172) 85.4% to 94.2% NPV 97.3% (818/841) 95.9% to 98.2% a Of the 16 specimens with false positive cobas Liat Cdiff test results relative to composite reference culture, 14 were positive by an FDA-cleared NAAT for tcdB DNA. b Of the 23 specimens with false negative cobas Liat Cdiff test results relative to composite reference culture, 19 were negative, three were positive, and one had an invalid test result by an FDA-cleared NAAT for tcdB DNA. 14 Comparison with Direct Culture The performance of the cobas Liat Cdiff test compared to direct culture is shown in Table. The positive percent agreement (PPA) and negative percent agreement (NPA) of the cobas Liat Cdiff test compared to the direct culture for all 1,013 specimens were 94.6% (139/147) and 96.2% (833/866), respectively. Of the eight specimens with false-negative cobas Liat Cdiff test results relative to direct culture, seven were negative and one was positive by a second NAAT method. Of the 33 specimens with false-positive cobas Liat Cdiff test results relative to direct culture, only 17 were tested with the second NAAT method: 14 were positive and three were negative by that second NAAT method. The remaining 16/33 specimens were positive by enriched culture and hence not tested with the second NAAT method per the discrepant analysis protocol. Table 10. Comparison with Direct Culture Direct Culture Result Positive Negative Total cobas Liat Cdiff Test Result Detected 139 33 172 Not Detected 8 833 841 Total 147 866 1013 95% CI PPA 94.6% (139/147) 89.6% to 97.2% NPA 96.2% (833/866) 94.7% to 97.3% b. Clinical specificity: See section M3a c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: In the prospective clinical study, 1013 samples were collected from a population that was 47.7% male (n=483) and 52.3% female (n=530) with a mean age of 57 years. The percentage of positive results observed with the cobas Liat Cdiff test in this population was 17%. 15 N. Instrument Name: cobas Liat System O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ____X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ___X_____ or No ________ 3. Specimen Identification: A sample barcode is scanned or a sample ID entered into the cobas Liat System during the assay run process. After scanning the sample barcode, the corresponding sample is loaded directly into a cobas Liat Tube using a transfer pipette. After the tube is capped, the tube barcodes is scanned by the cobas Liat System and the tube is inserted into the system to start the test. 4. Specimen Sampling and Handling: Specimen sampling and handling during the assay is controlled automatically using multiple sample processing modules contained within the cobas Liat System. The sample processing modules are composed of two assemblies, a moving side assembly comprised of multiple sample processing plungers and clamps and a fixed side assembly. When performing an assay, a cobas Liat Tube is inserted into the tube slot of a cobas Liat System. The plungers and clamps selectively compress the cobas Liat Tube segments against the fixed side assembly to release reagents from the segments, move the sample from one segment to another, and control reaction conditions. 5. Calibration: Not required. The cobas Liat Tube is single use and part of a closed system. 16 6. Quality Control: An internal process control used in conjunction with procedural checks monitors instrument functionality, performance, fluidics, and result determination based on a pre- defined decision algorithm. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Not applicable Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK171770_s6000_e8000

K171770.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

88 fresh remnant specimens were prospectively collected from symptomatic patients suspected of CDI. Of these, 172 were excluded according to the criteria for enrollment, storage, or cobas Liat Cdiff test processing as defined in the protocol. Of the 1,016 specimens tested with the cobas Liat Cdiff test, 1.4% 13 (14/1016) were initially invalid and 0.2% (2/1016) initially had failed results. After one retest per invalid or failed result following the labeled instructions, the final invalid rate was 0.1% (1/1016) and the final failed rate was 0% (0/1016). The three repeat invalid test results were excluded from the final performance analysis. A total of 1,013 evaluable specimens were included in the study from 483 males (47.7%) and 530 females (52.3%) with a median age of 59 years (range 5 to 98). All 1,013 specimens had valid results for both combined direct and enrichment culture and the cobas Liat Cdiff test. Of the 1,013 specimens, 179 were positive for toxigenic C. difficile using the combined results from direct and enrichment toxigenic culture, for a prevalence of 17.7% for the study. Comparison with Combined Direct and Broth Enrichment Culture The clinical performance of the cobas Liat Cdiff test compared with the combined results of direct and enrichment toxigenic culture are shown in Table 9. The sensitivity and specificity of the cobas Liat Cdiff test were 87.2% (156/179; 95% CI: 81.5% to 91.3%) and 98.1% (818/834; 95% CI: 96.9% to 98.8%), respectively; and the PPV and NPV were 90.7% (95% CI: 85.4% to 94.2%) and 97.3% (95% CI: 95.9% to 98.2%), respectively. Of the 23 specimens with false-negative cobas Liat Cdiff test results relative to combined direct culture and enrichment culture, 19 were negative, three were positive and one was invalid by an FDA-cleared NAAT for tcdB DNA. Of the 16 specimens with false-positive cobas Liat Cdiff test results relative to combined direct and enrichment culture, 14 were positive and two were negative by the FDA-cleared NAAT. Table 9. Comparison with Combined Direct and Enriched Culture Combined Direct and Enrichment Culture Result Positive Negative Total cobas Liat Cdiff Test Result Detected 156 16a 172 Not Detected 23b 818 841 Total 179 834 1013 95% CI Sensitivity 87.2% (156/179) 81.5% to 91.3% Specificity 98.1% (818/834) 96.9% to 98.8% PPV 90.7% (156/172) 85.4% to 94.2% NPV 97.3% (818/841) 95.9% to 98.2% a Of the 16 specimens with false positive cobas Liat Cdiff test results relative to composite reference culture, 14 were positive by an FDA-cleared NAAT for tcdB DNA. b Of the 23 specimens with false negative cobas Liat Cdiff test results relative to composite reference culture, 19 were negative, three were positive, and one had an invalid test result by an FDA-cleared NAAT for tcdB DNA. 14 Comparison with Direct Culture The performance of the cobas Liat Cdiff test compared to direct culture is shown in Table. The positive percent agreement (PPA) and negative percent agreement (NPA) of the cobas Liat Cdiff test compared to the direct culture for all 1,013 specimens were 94.6% (139/147) and 96.2% (833/866), respectively. Of the eight specimens with false-negative cobas Liat Cdiff test results relative to direct culture, seven were negative and one was positive by a second NAAT method. Of the 33 specimens with false-positive cobas Liat Cdiff test results relative to direct culture, only 17 were tested with the second NAAT method: 14 were positive and three were negative by that second NAAT method. The remaining 16/33 specimens were positive by enriched culture and hence not tested with the second NAAT method per the discrepant analysis protocol. Table 10. Comparison with Direct Culture Direct Culture Result Positive Negative Total cobas Liat Cdiff Test Result Detected 139 33 172 Not Detected 8 833 841 Total 147 866 1013 95% CI PPA 94.6% (139/147) 89.6% to 97.2% NPA 96.2% (833/866) 94.7% to 97.3% b. Clinical specificity: See section M3a c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: Not applicable 5. Expected values/Reference range: In the prospective clinical study, 1013 samples were collected from a population that was 47.7% male (n=483) and 52.3% female (n=530) with a mean age of 57 years. The percentage of positive results observed with the cobas Liat Cdiff test in this population was 17%. 15 N. Instrument Name: cobas Liat System O. System Descriptions: 1. Modes of Operation: Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? Yes ____X____ or No ________ Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? Yes ________ or No ____X____ 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes ___X_____ or No ________ 3. Specimen Identification: A sample barcode is scanned or a sample ID entered into the cobas Liat System during the assay run process. After scanning the sample barcode, the corresponding sample is loaded directly into a cobas Liat Tube using a transfer pipette. After the tube is capped, the tube barcodes is scanned by the cobas Liat System and the tube is inserted into the system to start the test. 4. Specimen Sampling and Handling: Specimen sampling and handling during the assay is controlled automatically using multiple sample processing modules contained within the cobas Liat System. The sample processing modules are composed of two assemblies, a moving side assembly comprised of multiple sample processing plungers and clamps and a fixed side assembly. When performing an assay, a cobas Liat Tube is inserted into the tube slot of a cobas Liat System. The plungers and clamps selectively compress the cobas Liat Tube segments against the fixed side assembly to release reagents from the segments, move the sample from one segment to another, and control reaction conditions. 5. Calibration: Not required. The cobas Liat Tube is single use and part of a closed system. 16 6. Quality Control: An internal process control used in conjunction with procedural checks monitors instrument functionality, performance, fluidics, and result determination based on a pre- defined decision algorithm. P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above: Not applicable Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK152495_s0_e2000

K152495.txt

purpose for submission

Addition of an over-the-counter (OTC) claim

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Purpose for submission:

idK152495_s0_e2000

K152495.txt

measurand

Propoxyphene

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Measurand:

idK152495_s0_e2000

K152495.txt

type of test

Qualitative immunochromatographic assay

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Type of test:

idK152495_s0_e2000

K152495.txt

classification

Class II

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Classification:

idK152495_s0_e2000

K152495.txt

product code

JXN

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Product code:

idK152495_s0_e2000

K152495.txt

panel

Toxicology, 91

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Panel:

idK152495_s0_e2000

K152495.txt

intended use

See Indications for Use below.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Intended use:

idK152495_s0_e2000

K152495.txt

predicate device name

Wondfo Propoxyphene Urine Test

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Predicate device name:

idK152495_s0_e2000

K152495.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK152495_s0_e2000

K152495.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK152495_s0_e2000

K152495.txt

applicant

Guangzhou Wondfo Biotech Co., Ltd.

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Applicant:

idK152495_s0_e2000

K152495.txt

proprietary and established names

Wondfo Propoxyphene Urine Test

IAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proprietary and established names:

idK152495_s0_e2000

K152495.txt

regulation section

21 CFR §862.3700

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE A. 510(k) Number: k152495 B. Purpose for Submission: Addition of an over-the-counter (OTC) claim C. Measurand: Propoxyphene D. Type of Test: Qualitative immunochromatographic assay E. Applicant: Guangzhou Wondfo Biotech Co., Ltd. F. Proprietary and Established Names: Wondfo Propoxyphene Urine Test G. Regulatory Information: 1. Regulation section: 21 CFR §862.3700 2. Classification: Class II 3. Product code: JXN 4. Panel: Toxicology, 91 2 H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indication(s) for use: The Wondfo Propoxyphene Urine Test is an immunochromatographic assay for the qualitative determination of d-Propoxyphene in human urine at a cutoff concentration of 300 ng/mL. The test is available in a dip card format and a test cup format. It is intended for prescription use and over the counter use. The test provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. The test will yield preliminary positive results when the prescription drug d-propoxyphene is ingested, even at or above therapeutic doses. There is no uniformly recognized cutoff concentration for d-Propoxyphene. It is not intended to distinguish between prescription use or abuse of this drug. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. 3. Special conditions for use statement(s): For over-the-counter and prescription use. 4. Special instrument requirements: Not applicable. The device is a visually read single-use device. I. Device Description: The Wondfo Propoxyphene Urine Test is a rapid test for the qualitative detection of Propoxyphene in urine samples. The device has two formats – test cup and dip card. The test cup comprises two items - a urine storage/transport vial and an integrated a urine collection cup with a lateral flow device. The dip card comprises three items – urine collection cup, urine storage/transport vial, and lateral flow test device. Both devices are single-use and visually read. J. Substantial Equivalence Information: 1. Predicate device name(s): 3 Wondfo Propoxyphene Urine Test 2. Predicate 510(k) number(s): k121557 3. Comparison with predicate: Similarities Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Indications for Use For the qualitative determination of Propoxyphene in human urine. Same Methodology Competitive binding, lateral flow immunochromatographic assay. Same Specimen Type Urine Same Cut-off value 300 ng/mL Same Test format Test Cup, Dip Card Same Assay type Qualitative Same Differences Item Candidate Device k152495 Wondfo Propoxyphene Urine Test Predicate Device k121557 Wondfo Propoxyphene Urine Test Special Conditions for Use OTC and prescription use. Prescription use. K. Standard/Guidance Document Referenced (if applicable): None were referenced. L. Test Principle: The assay type is a competitive immunoassay constructed on a lateral flow device. Each assay uses a mouse monoclonal anti-drug antibody-dye conjugate, fixed drug-protein conjugates, and anti-mouse IgG polyclonal antibodies coated on the test membranes. When the absorbent end of the test is immersed into a urine sample, the urine is absorbed into the 4 device by capillary action and mixes with the antibody-dye conjugate, flowing across the pre- coated membrane. At analyte concentrations below the target cut-off, antibody-dye conjugates bind to the drug-protein conjugate immobilized in the Test Region (T) of the device. This produces a colored test line that indicates a negative result. When analyte concentration is above the cut-off, analyte molecules bind to the antibody-dye conjugate, preventing the antibody-dye conjugate from binding to the drug-protein conjugate immobilized in the Test Region (T) of the device. No colored band shows in the test region, indicating a potentially positive result. A band should form in the control region (C) of the device regardless of the presence of drug or metabolite in the sample. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Performance characteristics are found in the predicate, k121557. b. Linearity/assay reportable range: Not applicable, the device is intended for qualitative use. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Control materials: External control standards are not supplied with this device; however, this device has internal procedural control. A colored line appearing in the control region confirms sufficient sample volume and adequate membrane wicking. Users are instructed that the test is invalid if a line fails to appear in the control region. d. Detection limit: See k121557. e. Analytical specificity: See k121557. f. Assay cut-off: See k121557. 5 2. Comparison studies: a. Method comparison with predicate device: See k121557. b. Matrix comparison: Not applicable. The assay is intended for urine samples. 3. Clinical studies: a. Clinical Sensitivity: Not applicable. b. Clinical specificity: Not applicable. c. Other clinical supportive data (when a. and b. are not applicable): Consumer / lay person study: The lay user study was comprised of 280 lay users who were divided into two groups to test the Dipcard format and the Test Cup format (140 each). The testing was conducted at three intended user sites: one hospital and two drug addiction recovery centers in P.R. China. All participants came from diverse educational and occupational backgrounds. Only one of the 280 participants indicated that they had previous experience in drugs of abuse testing. In the group testing with the Test Cup, there were 77 male and 63 female participants with ages ranging from 21 to 62 years of age. In the group testing with the Dipcard, there were 73 male and 67 female participants with ages ranging from 21 to 64 years of age. The samples were urine and prepared at the following concentrations; -100%, +/- 75%, +/-50%, +/-25% of the cut-off by spiking Propoxyphene into drug free, pooled urine specimens. The concentrations of the samples were confirmed by gas chromatography/ mass spectrometry. Each urine sample was aliquoted into individual containers, blind-labeled, and randomized. Each participant was provided with the package insert, 1 blind labeled sample, and a Wondfo Propoxyphene Urine Test for a Dip card or Test cup. The test procedure was conducted solely based on the users reading and understanding of the package insert. After the test, the consumer was required to fill out questionnaire on the ease of 6 understanding the package insert instructions. A Flesch-Kincaid reading analysis was performed on the package insert and the score revealed a reading grade level of less than 7. All lay users indicated that the device instructions can be easily followed. The results are summarized below: Comparison between Test Cup and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% Comparison between Dip Card and GC/MS % of Cut- off Number of samples Propoxyphene Concentration by GC/MS Lay Person Results Correct results No. of Positive No. of Negative -100% 20 0 0 20 100% -75% 20 75 0 20 100% -50% 20 148 0 20 100% -25% 20 226 2 18 90% +25% 20 378 18 2 90% +50% 20 452 20 0 100% +75% 20 523 20 0 100% 4. Clinical cut-off: Not applicable. 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. 7 O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Regulation section:

idK162705_s0_e2000

K162705.txt

purpose for submission

To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di.

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Purpose for submission:

idK162705_s0_e2000

K162705.txt

measurand

D-dimer

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Measurand:

idK162705_s0_e2000

K162705.txt

type of test

Quantitative

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Type of test:

idK162705_s0_e2000

K162705.txt

classification

Class II

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Classification:

idK162705_s0_e2000

K162705.txt

product code

GGN, Plasma, Coagulation Control

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Product code:

idK162705_s0_e2000

K162705.txt

panel

Hematology (81)

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Panel:

idK162705_s0_e2000

K162705.txt

predicate device name

VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Predicate device name:

idK162705_s0_e2000

K162705.txt

applicant

Maine Standards Company LLC

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Applicant:

idK162705_s0_e2000

K162705.txt

proprietary and established names

VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit

EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Proprietary and established names:

idK162705_s0_e2000

K162705.txt

regulation section

21 CFR 864.5425, Multipurpose system for in vitro coagulation studies

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K162705 B. Purpose for Submission: To expand the use of previously cleared VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit to the Diagnostica Stago STA-R® Evolution in combination with STA® - Liatest® D-Di. C. Measurand: D-dimer D. Type of Test: Quantitative E. Applicant: Maine Standards Company LLC F. Proprietary and Established Names: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit G. Regulatory Information: 1. Regulation section: 1 21 CFR 864.5425, Multipurpose system for in vitro coagulation studies 2. Classification: Class II 3. Product code: GGN, Plasma, Coagulation Control 4. Panel: Hematology (81) H. Intended Use: 1. Intended use: 2 VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit solutions are assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. 2. Indication(s) for use: Same as Intended use 3. Special conditions for use statement: For prescription use only 4. Special instrument requirements: Diagnostica Stago STA-R® Evolution (K093001) STA® - Liatest D-Di (K162227) I. Device Description: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of assayed quality control materials used to verify the relationship between the theoretical and actual quantitative performance of D-Dimer. Each VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit consists of a five level set of D-Dimer in a human plasma based matrix, each level containing 3.0 mL. J. Substantial Equivalence Information: 1. Predicate device name: VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit 2. Predicate 510(k) number: K152961 3. Comparison with predicate: 3 Similarities Item Device VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Predicate VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit Intended Use For in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling. Same Analyte D-Dimer Same Stability Shelf-life: 4 months Closed-vial: 9 months at -10 to -25°C Open-vial: maximum of 4 freeze/thaw cycles when stored at -10 to -25°C between cycles Same Matrix Human plasma Same Number of levels 5 levels Same Preparation Liquid; ready to use Same There is no difference between the subject device and the predicate. K. Standard/Guidance Document Referenced (if applicable): CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline–Third Edition CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach; Approved Guideline CLSI EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline L. Test Principle: The VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit is an analyte set of D- Dimer in human plasma base matrix which contains five liquid levels. The test kit is used to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. M. Performance Characteristics (if/when applicable): 1. Analytical performance: 4 a. Precision/Reproducibility: To obtain measures of repeatability and within-laboratory precision, three VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lots (levels 1–5) were analyzed in a single-site study performed over 20 operating days, two runs per day and two replicates per run for each level. Testing was performed on one STA-R® Evolution analyzer using a single lot of STA® - Liatest® D-Di. To demonstrate precision performance, %CV and SD of within-run, between-run, between-day, and within-laboratory (total) were calculated. The repeatability study met the pre- determined acceptance criteria. Results from the study are provided in the table below. Level 1 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 0.44 0.080 18.5 0.000 0.0 0.027 6.2 0.086 19.5 Lot 2 0.46 0.055 11.8 0.015 3.2 0.030 6.5 0.064 13.8 Lot 3 0.46 0.057 12.6 0.043 9.4 0.045 9.8 0.085 18.6 Level 2 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.15 0.055 4.7 0.000 0.0 0.016 1.4 0.057 4.9 Lot 2 1.15 0.054 4.7 0.013 1.2 0.025 2.2 0.061 5.3 Lot 3 1.14 0.051 4.4 0.019 1.7 0.016 1.4 0.057 4.9 Level 3 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 1.88 0.059 3.1 0.024 1.3 0.000 0.0 0.064 3.4 Lot 2 1.92 0.042 2.2 0.000 0.0 0.036 1.9 0.055 2.9 Lot 3 1.88 0.060 3.2 0.000 0.0 0.041 2.2 0.072 3.9 Level 4 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 2.68 0.117 4.4 0.000 0.0 0.068 2.5 0.135 5.0 Lot 2 2.67 0.067 2.5 0.380 1.4 0.000 0.0 0.077 2.9 Lot 3 2.67 0.136 5.1 0.000 0.0 0.54 2.0 0.146 5.5 Level 5 Mean µg/mL FEU Within-run Between-run Between-day Total SD %CV SD %CV SD %CV SD %CV D-Dimer Lot 1 3.53 0.171 4.8 0.000 0.0 0.000 0.0 0.171 4.8 Lot 2 3.56 0.168 4.7 0.000 0.0 0.077 2.2 0.185 5.2 Lot 3 3.56 0.080 2.2 0.058 1.6 0.051 1.4 0.111 3.1 To obtain measures of reproducibility, a single VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit lot (levels 1-5) was analyzed over five operating days, one run per day, five replicates per run across two sites. Each site performed testing on three STA-R® Evolution analyzers. 5 Level Mean µg/mL FEU Within-run Within- Laboratory Reproducibility SD %CV SD %CV SD %CV Level 1 0.44 0.061 13.8% 0.066 15.0% 0.069 15.5% Level 2 1.14 0.054 4.7% 0.054 4.7% 0.063 5.5% Level 3 1.87 0.065 3.5% 0.065 3.5% 0.089 4.7% Level 4 2.64 0.052 2.0% 0.059 2.2% 0.081 3.1% Level 5 3.50 0.275 7.9% 0.282 8.1% 0.3 1.2% b. Linearity/assay reportable range: Linearity for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit was completed on the Stago STA-R® Evolution instrument. Linearity performance was confirmed for the D-Dimer analyte by manual method and a software derived method using Analyze-IT® Regulation section:

idK162705_s2000_e4000

K162705.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

D-dimer concentrations of each measured value of the five levels plotted vs. five assigned levels of concentration. The results provided appeared to be linear. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: Not applicable. An international reference preparation (IRP) is not available for D- dimer assays. Value Assignment A linear relationship exists between levels 1 through 5 of each VALIDATE® D- Dimer Calibration Verification/Linearity Test Kit; level 1 being the lowest concentration and level 5 being the highest concentration. Levels 1 and 5 are prepared independently by the addition of D-dimer to a human plasma base. The D- dimer is prepared by Maine Standards from fresh frozen human plasma. Intermediate levels 2, 3, and 4 are subsequently prepared from levels 1 and 5 by equal part dilutions. Testing was performed for each level on five separate days, six replicates per day for a total of 30 replicates per level. Total percent coefficient of variation (%CV) was calculated for levels 1 and 5, and found to be within the predefined acceptance criteria. Typical mean recovery values for all levels for one representative lot tested using the STA® - Liatest D-Di reagent kit in combination with the STA-R® Evolution are presented in the table below. VALIDATE D-DIMER Level 1 Level 2 Level 3 Level 4 Level 5 D-dimer (µg/mL FEU) 0.32 1.05 1.78 2.50 3.23 Shelf-life and Open-Vial Stability Testing 6 A real-time stability study was performed to support the shelf-life claim for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit. Stability was evaluated on the STA-R® Evolution using three lots of VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit. Acceptance criteria were found to be acceptable and support the shelf-life stability claim of 4 months from the date of manufacturing (DOM) when stored at -10 to -25°C. A freeze/thaw stability assessment was also conducted to support the open-vial stability claim. Acceptance criteria were found to be acceptable to support four freeze/thaw events. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: 7 Not applicable 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK162705_s2000_e4000

K162705.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

. The D-dimer concentrations of each measured value of the five levels plotted vs. five assigned levels of concentration. The results provided appeared to be linear. c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: Not applicable. An international reference preparation (IRP) is not available for D- dimer assays. Value Assignment A linear relationship exists between levels 1 through 5 of each VALIDATE® D- Dimer Calibration Verification/Linearity Test Kit; level 1 being the lowest concentration and level 5 being the highest concentration. Levels 1 and 5 are prepared independently by the addition of D-dimer to a human plasma base. The D- dimer is prepared by Maine Standards from fresh frozen human plasma. Intermediate levels 2, 3, and 4 are subsequently prepared from levels 1 and 5 by equal part dilutions. Testing was performed for each level on five separate days, six replicates per day for a total of 30 replicates per level. Total percent coefficient of variation (%CV) was calculated for levels 1 and 5, and found to be within the predefined acceptance criteria. Typical mean recovery values for all levels for one representative lot tested using the STA® - Liatest D-Di reagent kit in combination with the STA-R® Evolution are presented in the table below. VALIDATE D-DIMER Level 1 Level 2 Level 3 Level 4 Level 5 D-dimer (µg/mL FEU) 0.32 1.05 1.78 2.50 3.23 Shelf-life and Open-Vial Stability Testing 6 A real-time stability study was performed to support the shelf-life claim for the VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit. Stability was evaluated on the STA-R® Evolution using three lots of VALIDATE® D-Dimer Calibration Verification/Linearity Test Kit. Acceptance criteria were found to be acceptable and support the shelf-life stability claim of 4 months from the date of manufacturing (DOM) when stored at -10 to -25°C. A freeze/thaw stability assessment was also conducted to support the open-vial stability claim. Acceptance criteria were found to be acceptable to support four freeze/thaw events. d. Detection limit: Not applicable e. Analytical specificity: Not applicable f. Assay cut-off: Not applicable 2. Comparison studies: a. Method comparison with predicate device: Not applicable b. Matrix comparison: Not applicable 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable 4. Clinical cut-off: 7 Not applicable 5. Expected values/Reference range: Not applicable. N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK143467_s0_e2000

K143467.txt

purpose for submission

New device

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Purpose for submission:

idK143467_s0_e2000

K143467.txt

measurand

Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Measurand:

idK143467_s0_e2000

K143467.txt

type of test

Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD)

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Type of test:

idK143467_s0_e2000

K143467.txt

classification

Class II

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Classification:

idK143467_s0_e2000

K143467.txt

panel

Clinical Chemistry (75)

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Panel:

idK143467_s0_e2000

K143467.txt

intended use

See Indications for Use below.

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Intended use:

idK143467_s0_e2000

K143467.txt

predicate device name

FORA GD40 Blood Glucose Monitoring System

STANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Predicate device name:

idK143467_s0_e2000

K143467.txt

applicant

TaiDoc Technology Corporation

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Applicant:

idK143467_s0_e2000

K143467.txt

proprietary and established names

FORA GD43 Blood Glucose Monitoring System

IAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Proprietary and established names:

idK143467_s0_e2000

K143467.txt

regulation section

21 CFR 862.1345, Glucose test system

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE A. 510(k) Number: k143467 B. Purpose for Submission: New device C. Measurand: Capillary whole blood glucose from the fingertip, palm, forearm, and upper arm D. Type of Test: Quantitative amperometric assay, glucose dehydrogenase (GDH-FAD) E. Applicant: TaiDoc Technology Corporation F. Proprietary and Established Names: FORA GD43 Blood Glucose Monitoring System G. Regulatory Information: 1. Regulation section: 21 CFR 862.1345, Glucose test system 2. Classification: Class II 3. Product code: NBW, System, Test, Blood Glucose, Over the Counter LFR, Glucose Dehydrogenase, Glucose 4. Panel: Clinical Chemistry (75) H. Intended Use: 1. Intended use(s): See Indications for Use below. 2. Indications(s) for use: The FORA GD43 Blood Glucose Monitoring System is intended to be used for the quantitative measurement of glucose (sugar) in fresh capillary whole blood from the 2 fingertip and alternative sites (palm, forearm and upper arm).This blood glucose monitoring system is intended to be used by a single person and should not be shared. Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly). The FORA GD43 Blood Glucose Monitoring System is intended for self-testing outside the body (in vitro diagnostic use) by people with diabetes at home as an aid to monitor the effectiveness of diabetes control. This system should not be used for the diagnosis of or screening for diabetes, nor for use on neonates. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). 3. Special conditions for use statement(s): · For in vitro diagnostic use only · Not for use in diagnosis or screening of diabetes mellitus · Not for neonatal use · Not for use on patients who are dehydrated, hypotensive, in shock, or for individuals in hyperglycemic-hyperosmolar state, with or without ketosis. · Not for use in critically ill patients · Alternative site testing (AST) should only be done during steady-state times (when glucose is not changing rapidly) · Alternative site testing results should not be used to calibrate continuous glucose monitors (CGMs) · Alternative site testing results should not be used in insulin dosing calculations 4. Special instrument requirements: FORA GD43 Blood Glucose Meter I. Device Description: The FORA GD43 Blood Glucose Monitoring System consists of the FORA GD43 Blood Glucose Meter, Owner’s Manual, Protective Wallet, Quick Start User Guide, Daily Log Book, Warranty Card and 2 x 1.5 V AAA alkaline batteries. The FORA GD43 Test Strips are for use with the FORA GD43 Blood Glucose Meters to quantitatively measure glucose (sugar) in fresh capillary whole blood from the fingertip and alternative sites (palm, forearm and upper arm). The FORA GD43 Test Strips need to be purchased separately. The control solutions to be used with the FORA GD43 System are the FORA Control Solutions, cleared in k093724. Three levels are available: Level 1, Level 2, and Level 3. Level 1 is included in some kit configurations and all levels can be purchased separately. The Clever Chek Health Care System Software is an optional software accessory for use with the FORA GD43 Blood Glucose Monitoring System, which provides enhanced data management capabilities. 3 J. Substantial Equivalence Information: 1. Predicate device name(s): FORA GD40 Blood Glucose Monitoring System 2. Predicate 510(k) number(s): k101509 3. Comparison with predicate: Similarities Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Indications for Use/Intended Use To quantitatively measure glucose (sugar) in whole blood, as an aid in monitoring the effectiveness of glucose control. Same Enzyme Glucose Dehydrogenase (GDH-FAD) Same Test Method Amperometric detection Same Measuring Range 20-600 mg/dL Same Reaction time 5 sec Same Memory Capacity 1000 data points Same Dimensions 110.0 L/57.0 W/25.0 H (mm) Same Weight 71g without battery Same Differences Predicate FORA GD40 Blood Glucose Monitoring System (k101509) Candidate FORA GD43 Blood Glucose Monitoring System (k143467) Sample type Capillary whole blood from finger Capillary whole blood from fingertip, palm, forearm, and upper arm Electrode carbon gold Sample volume 1.1uL 0.5uL Hematocrit range 20-60% 20-70% Test Strip stability Opened - 3 months Unopened - 18 months Opened - 24 months Unopened - 24 months Operating conditions 50°F - 104°F (10°C - 40°C) 46.4°F - 113°F (8°C - 45°C) K. Standard/ Guidance Document Referenced (if applicable): · ISO 14971: Medical Devices - Application of risk management to medical devices 4 · IEC 62304: Medical device software - Software lifecycle processes · IEC 61010-1, Safety requirements for electrical equipment for measurement, control, and laboratory use - Part 1: General requirements · IEC 61010-2, Safety requirements for electrical equipment for measurement, control, and laboratory use – Part 2-101: Particular requirements for in vitro diagnostic (IVD) medical equipment · IEC 61326-1, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 1: General requirements · IEC 61326-2-6, Electrical equipment for measurement, control and laboratory use - EMC requirements - Part 2-6: Particular requirements – In vitro diagnostic (IVD) medical equipment · IEC 60601-1-2, Medical electrical equipment - part 1-2: general requirements for basic safety and essential performance - collateral standard: electromagnetic compatibility - requirements and tests · CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. · CLSI EP7-A2, Interference Testing in Clinical Chemistry; Approved Guideline. · CLSI EP6-P, Evaluation of the Linearity of Quantitative Analytical Methods L. Test Principle: The test is based on the measurement of electrical current generated by the reaction of glucose with the reagent of the strip. The meter utilizes the current signal to calculate the blood glucose level. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: Repeatability studies (within-day precision) were performed with venous whole blood samples at five glucose concentration ranges (30-50 mg/dL, 51-110 mg/dL, 111-150 mg/dL, 151-250 mg/dL, 251-400 mg/dL) using 3 test strip lots. Ten runs were performed on each sample across the three test strip lots with 10 replicates per run resulting in a total of 100 replicates collected for each glucose level. Results are summarized below: Glucose Level 30-50 (mg/dL) 51-110 (mg/dL) 111-150 (mg/dL) Test Strip Lot 1 2 3 1 2 3 1 2 3 Mean (mg/dL) 44.3 45.4 44.7 84.4 85.3 84.7 132.7 136.8 134.8 SD 1.60 1.33 1.48 1.99 2.36 1.94 3.04 3.64 3.71 CV% 3.61 2.93 3.32 2.36 2.77 2.29 2.29 2.66 2.75 N 30 30 40 30 30 40 30 30 40 5 Glucose Level 151-250 (mg/dL) 251-400 (mg/dL) Test Strip Lot 1 2 3 1 2 3 Mean (mg/dL) 199.7 199.2 199.1 357.8 365.7 360.7 SD 4.83 4.96 4.94 11.53 13.90 13.67 CV% 2.42 2.49 2.48 3.22 3.80 3.79 N 30 30 40 30 30 40 Intermediate precision (day-to-day precision) was evaluated using three glucose control solutions. Ten strip vials, from three test strip lots, were assigned to each of the three control levels (30-50mg/dL, 96-144 mg/dL, 280-420 mg/dL). From each strip vial, a test was performed on each of the 3 control level solutions for 10 days. A total of 10 replicates were collected per glucose level tested per day for a total of 100 measurements per glucose level tested across the three test strip lots. Results are summarized below: Glucose Level Level 1 (30-50 mg/dL) Level 2 (96-144 mg/dL) Level 3 (280-420 mg/ Regulation section:

idK143467_s4000_e6000

K143467.txt

proposed labeling

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

76.6% (95/124) 95.2% (118/124) 100% (124/124) Regression Analysis Results: Lay-user vs reference method: Site slope 95% CI of slope intercept 95% CI of intercept R2 Fingertip 0.9867 0.9661~1.0072 2.3097 -1.7874~6.4068 0.9838 Palm 0.9907 0.9685~1.0130 0.8984 -3.5421~5.3389 0.9812 Forearm 0.9883 0.9658~1.0107 1.5578 -2.9178~6.0334 0.9808 Upper arm 0.9962 0.9746~1.0179 2.7011 -1.6154~7.0175 0.9824 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: Time of day People without diabetes Fasting and before meals <100 mg/dL 2 hours after meals <140 mg/dL American Diabetes Association (2014), Clinical Practice Recommendations, Diabetes Care, 37 (Supplement 1): S16 10 N. Instrument Name: FORA GD43 Blood Glucose Meter O. System Description: 1. Modes of Operation: Each test strip is single use and must be replaced with a new strip for additional readings. Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device?: Yes X or No . Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission?: Yes or No X . 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes X or No . The applicant has provided documentation that indicates the device was designed and developed under good software life-cycle processes. 3. Specimen Identification: There is no sample identification function with this device. Samples are applied directly to the test strip as they are collected. 4. Specimen Sampling and Handling: This device is intended to be used with capillary whole blood from the fingertip, palm, forearm, and upper arm. There is not patient identification with this system. 5. Calibration: Calibration is automatic. The user only needs to verify the code number displayed on the meter matches with the code number on the test strip vial before use. 6. Quality Control: The FORA Control Solutions are used as quality control checks to make sure that the meter and test strips are working correctly and that the user is performing the test correctly. The labeling provides instructions on when quality control testing should be performed. The control ranges are printed on the test strip vial label. 11 P. Other Supportive Instrument Performance Characteristics Data Not Covered In the “Performance Characteristics” Section above: 1) Hematocrit study: The effect of different hematocrit levels was evaluated using venous whole blood samples with hematocrit levels of 20 - 70% (20, 30, 40, 50, 60 and 70%) spiked with glucose to achieve target concentrations of 40.5, 102.5, 142.5, and 356 mg/dL with 3 lots of test strips. A total of 30 replicates were performed for each combination of strip lot, glucose concentration, and hematocrit level tested. The results demonstrated that the FORA GD43 Blood Glucose Monitoring System produces accurate results over the claimed hematocrit range of 20-70%. 2) Altitude study: To evaluate the effects of altitude on the FORA GD43 system results, venous blood samples from three donors were altered to 5 glucose concentrations (66, 121, 230, 375 and 560 mg/dL) and tested at various levels of atmospheric pressure and pO2 levels in a glove box to simulate equivalent altitudes from sea level to 15,000 feet above sea level. The meter results were compared to those obtained with the YSI-2300 analyzer. The results demonstrate acceptable bias to the reference to support the claims in the labeling that altitudes up to 15,000 feet have no significant effect on blood glucose measurements from the FORA GD43 Blood Glucose Monitoring System. 3) Temperature and humidity studies: The sponsor performed temperature and humidity studies using venous blood samples at target glucose concentrations of 65, 125, and 320 mg/dL to evaluate temperatures ranging from 46-113°F (8-45°C) and relative humidity from 10-90%. Extreme combinations of the claimed temperature and humidity operating conditions were evaluated and meter results compared to a reference method. The results support the claimed range of operating conditions: 46-113°F and 10-90% relative humidity. 4) Sample volume study: The sponsor performed a sample volume study to support the claimed minimum sample volume requirement for the FORA GD43 system (0.5 mL) using blood samples at three glucose concentrations (42.5, 128, 319 mg/dL). Results support the claimed sample volume of 0.5 mL. 5) Infection Control Studies: The device is intended for single-patient use. Disinfection efficacy studies were performed on the materials comprising the meter by an outside commercial testing laboratory demonstrating complete inactivation of hepatitis B virus (HBV) with the chosen disinfectant, MicroKill+ Disinfectant Wipes (EPA registration #598940-10- 37549). Robustness studies were also performed by the sponsor demonstrating that there was no change in performance or external materials of the meter after 260 cleaning and disinfection cycles (520 wipes). The robustness studies were designed to simulate 5 12 years of single-patient use. Labeling was reviewed for adequate instructions for the validated cleaning and disinfection procedures. 6) Electromagnetic Compatibility (EMC) testing was performed and found to be adequate for the FORA GD43 system. 7) FORA Customer Service is available from 7am to 6pm PST, Monday through Friday by calling 1-888-307-8188. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Proposed labeling:

idK143467_s4000_e6000

K143467.txt

conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

124) 76.6% (95/124) 95.2% (118/124) 100% (124/124) Regression Analysis Results: Lay-user vs reference method: Site slope 95% CI of slope intercept 95% CI of intercept R2 Fingertip 0.9867 0.9661~1.0072 2.3097 -1.7874~6.4068 0.9838 Palm 0.9907 0.9685~1.0130 0.8984 -3.5421~5.3389 0.9812 Forearm 0.9883 0.9658~1.0107 1.5578 -2.9178~6.0334 0.9808 Upper arm 0.9962 0.9746~1.0179 2.7011 -1.6154~7.0175 0.9824 4. Clinical cut-off: Not Applicable 5. Expected values/Reference range: Time of day People without diabetes Fasting and before meals <100 mg/dL 2 hours after meals <140 mg/dL American Diabetes Association (2014), Clinical Practice Recommendations, Diabetes Care, 37 (Supplement 1): S16 10 N. Instrument Name: FORA GD43 Blood Glucose Meter O. System Description: 1. Modes of Operation: Each test strip is single use and must be replaced with a new strip for additional readings. Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device?: Yes X or No . Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission?: Yes or No X . 2. Software: FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: Yes X or No . The applicant has provided documentation that indicates the device was designed and developed under good software life-cycle processes. 3. Specimen Identification: There is no sample identification function with this device. Samples are applied directly to the test strip as they are collected. 4. Specimen Sampling and Handling: This device is intended to be used with capillary whole blood from the fingertip, palm, forearm, and upper arm. There is not patient identification with this system. 5. Calibration: Calibration is automatic. The user only needs to verify the code number displayed on the meter matches with the code number on the test strip vial before use. 6. Quality Control: The FORA Control Solutions are used as quality control checks to make sure that the meter and test strips are working correctly and that the user is performing the test correctly. The labeling provides instructions on when quality control testing should be performed. The control ranges are printed on the test strip vial label. 11 P. Other Supportive Instrument Performance Characteristics Data Not Covered In the “Performance Characteristics” Section above: 1) Hematocrit study: The effect of different hematocrit levels was evaluated using venous whole blood samples with hematocrit levels of 20 - 70% (20, 30, 40, 50, 60 and 70%) spiked with glucose to achieve target concentrations of 40.5, 102.5, 142.5, and 356 mg/dL with 3 lots of test strips. A total of 30 replicates were performed for each combination of strip lot, glucose concentration, and hematocrit level tested. The results demonstrated that the FORA GD43 Blood Glucose Monitoring System produces accurate results over the claimed hematocrit range of 20-70%. 2) Altitude study: To evaluate the effects of altitude on the FORA GD43 system results, venous blood samples from three donors were altered to 5 glucose concentrations (66, 121, 230, 375 and 560 mg/dL) and tested at various levels of atmospheric pressure and pO2 levels in a glove box to simulate equivalent altitudes from sea level to 15,000 feet above sea level. The meter results were compared to those obtained with the YSI-2300 analyzer. The results demonstrate acceptable bias to the reference to support the claims in the labeling that altitudes up to 15,000 feet have no significant effect on blood glucose measurements from the FORA GD43 Blood Glucose Monitoring System. 3) Temperature and humidity studies: The sponsor performed temperature and humidity studies using venous blood samples at target glucose concentrations of 65, 125, and 320 mg/dL to evaluate temperatures ranging from 46-113°F (8-45°C) and relative humidity from 10-90%. Extreme combinations of the claimed temperature and humidity operating conditions were evaluated and meter results compared to a reference method. The results support the claimed range of operating conditions: 46-113°F and 10-90% relative humidity. 4) Sample volume study: The sponsor performed a sample volume study to support the claimed minimum sample volume requirement for the FORA GD43 system (0.5 mL) using blood samples at three glucose concentrations (42.5, 128, 319 mg/dL). Results support the claimed sample volume of 0.5 mL. 5) Infection Control Studies: The device is intended for single-patient use. Disinfection efficacy studies were performed on the materials comprising the meter by an outside commercial testing laboratory demonstrating complete inactivation of hepatitis B virus (HBV) with the chosen disinfectant, MicroKill+ Disinfectant Wipes (EPA registration #598940-10- 37549). Robustness studies were also performed by the sponsor demonstrating that there was no change in performance or external materials of the meter after 260 cleaning and disinfection cycles (520 wipes). The robustness studies were designed to simulate 5 12 years of single-patient use. Labeling was reviewed for adequate instructions for the validated cleaning and disinfection procedures. 6) Electromagnetic Compatibility (EMC) testing was performed and found to be adequate for the FORA GD43 system. 7) FORA Customer Service is available from 7am to 6pm PST, Monday through Friday by calling 1-888-307-8188. Q. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. R. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Conclusion:

idK180886_s0_e2000

K180886.txt

purpose for submission

To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Purpose for submission:

idK180886_s0_e2000

K180886.txt

measurand

Delafloxacin 0.002-32 μg/mL

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Measurand:

idK180886_s0_e2000

K180886.txt

type of test

Quantitative Antimicrobial Susceptibility Test growth based detection

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Type of test:

idK180886_s0_e2000

K180886.txt

classification

Class II

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Classification:

idK180886_s0_e2000

K180886.txt

product code

JWY - Manual Antimicrobial Susceptibility Test Systems

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Product code:

idK180886_s0_e2000

K180886.txt

panel

83 – Microbiology

(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Panel:

idK180886_s0_e2000

K180886.txt

predicate device name

Liofilchem MTS, vancomycin

SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Predicate device name:

idK180886_s0_e2000

K180886.txt

applicant

Liofilchem s.r.l.

k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Applicant:

idK180886_s0_e2000

K180886.txt

proprietary and established names

Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL

ANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Proprietary and established names:

idK180886_s0_e2000

K180886.txt

regulation section

866.1640 Antimicrobial Susceptibility Test Powder

) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: K180886 B. Purpose for Submission: To obtain a substantial equivalence for the addition of Delafloxacin at concentrations of 0.002-32 µg/mL for susceptibility testing of non-fastidious Gram negative organisms C. Measurand: Delafloxacin 0.002-32 μg/mL D. Type of Test: Quantitative Antimicrobial Susceptibility Test growth based detection E. Applicant: Liofilchem s.r.l. F. Proprietary and Established Names: Liofilchem MIC Test Strip (MTS), Delafloxacin 0.002-32 μg/mL G. Regulatory Information: 1. Regulation section: 866.1640 Antimicrobial Susceptibility Test Powder 2. Classification: II 3. Product code: JWY - Manual Antimicrobial Susceptibility Test Systems 4. Panel: 83 – Microbiology 2 H. Intended Use: 1. Intended use(s): The Liofilchem® MIC Test Strip (MTS) is a quantitative method intended for the in vitro determination of antimicrobial susceptibility of bacteria. MTS consists of specialized paper impregnated with a pre-defined concentration gradient of an antimicrobial agent, which is used to determine the minimum inhibitory concentration (MIC) in μg/mL of antimicrobial agents against bacteria as tested on agar media using overnight incubation and manual reading procedures. The Delafloxacin MTS at concentrations of 0.002-32 μg/mL should be interpreted at 16- 20 hours of incubation. Delafloxacin has been shown to be active both clinically and in vitro against the non- fastidious bacteria listed below according to the FDA drug label: Gram-negative bacteria Escherichia coli Klebsiella pneumoniae Enterobacter cloacae Pseudomonas aeruginosa Delafloxacin has been shown to be active in vitro only against the non-fastidious bacteria listed below according to the FDA drug label: Klebsiella (Enterobacter) aerogenes Klebsiella oxytoca Proteus mirabilis 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): · For prescription use · The ability of the Liofilchem MIC Test Strip (MTS) to detect resistant isolates with the following drug/bacterial species combinations is unknown because resistant isolates were either not available or an insufficient number was encountered at the time of comparative testing. Delafloxacin: Klebsiella (Enterobacter) aerogenes 3 · Characterization of Topoisomerase IV and DNA gyrase quinolone-resistance determining regions (QRDRs) and altered efflux resistance mechanisms was not available for organisms at the time of comparative testing, and therefore the performance of Liofilchem MIC Test Strip Delafloxacin MTS for non-fastidious Gram negative bacilli with these resistance mechanisms is unknown for the following: Enterobacteriaceae, P. aeruginosa 4. Special instrument requirements: Manual reading only I. Device Description: The Delafloxacin MIC Test Strip (MTS) consists of specialized paper impregnated with a predefined concentration gradient of Delafloxacin across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. One side of the strip is labelled with the Delafloxacin code (DLX) and the MIC reading scale in µg/mL. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16- 20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the MIC Test Strip. Since MTS strip generates MIC values which fall between two-fold dilutions for interpretation, the MIC value read is recorded to the next two-fold dilution value. J. Substantial Equivalence Information: 1. Predicate device name(s): Liofilchem MTS, vancomycin 2. Predicate 510(k) number(s): K153687 4 3. Comparison with predicate: Table 1: Comparison with the Predicate Device Similarities Item Device Liofilchem MTS, Delafloxacin (K180886) Predicate Liofilchem MTS, vancomycin (K153687) Intended Use Quantitative susceptibility to antimicrobial agents Same Media Mueller Hinton agar Same Inoculation Isolated colonies from culture in suspension equivalent to 0.5 McFarland. Inoculum is applied manually using the manual plate inoculation method or plate rotator for even distribution of inoculum Same Reading Manual; the point where the edge of inhibition ellipse intersects the MIC Test Strip Same Result MIC Same Differences Item Device Liofilchem MTS, Delafloxacin (K171906) Predicate Liofilchem MTS, vancomycin (K153687) Antibiotic Delafloxacin code (DLX) Vancomycin code (VA) Incubation 35 ± 2°C for 16 - 20hrs 35 ± 2°C for 24 hours K. Standard/Guidance Document Referenced: · Guidance for Industry and FDA - Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems – August 28, 2009. · CLSI M07-A10 “Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, Tenth Edition January 2015”. · CLSI M100-S26 “Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fifth Informational Supplement, January 2016”. L. Test Principle: MTS are made of specialized paper impregnated with a predefined concentration gradient of antibiotic, across 15 two-fold dilutions similar to dilutions used by conventional MIC methods. When the MIC Test Strip is applied onto an inoculated agar surface, the preformed exponential gradient of antimicrobial agent is immediately transferred to the agar matrix. After 16-20 hours incubation, a symmetrical inhibition ellipse centered along the strip is formed. The MIC is read directly from the scale in terms of µg/mL at the point where the edge of the inhibition ellipse intersects the strip MIC Test Strip. 5 Growth along the entire gradient (i.e., no inhibition ellipse) indicates that the MIC value is greater than or equal to (≥) the highest value on the scale. An inhibition ellipse that intersects below the lower end of the scale is read as less than (<) the lowest value. An MIC of 0.125μg/mL is considered to be the same as 0.12μg/mL for reporting purposes. An MTS MIC value which falls between standard two-fold dilutions must be rounded up to the next standard upper two-fold value before categorization. M. Performance Characteristics: 1. Analytical performance: a. Precision/Reproducibility: Reproducibility testing was conducted at three sites using ten gram negative organisms. Each isolate was tested in triplicate over three days. The reproducibility panel included two E. coli, two K. pneumoniae, two E. cloacae, one P. mirabilis, and three P. aeruginosa isolates. The mode of MIC value was pre-determined and the reproducibility was calculated based on the number of MIC values that fell within ±1 doubling dilution of the mode. All MIC results were on scale. The testing resulted in overall reproducibility of greater than 95%. The results were acceptable. b. Linearity/assay reportable range: Not applicable c. Traceability, Stability, Expected values (controls, calibrators, or methods): Quality Control (QC) Testing: The QC isolates recommended by both FDA and CLSI, namely E. coli ATCC 25922 and P. aeruginosa ATCC 27853 were tested a sufficient number of times (i.e., at least 20/site) at each testing site using both MTS and reference methods. The results are summarized in Table 2 below. The quality control results are acceptable. 6 Table 2: Delafloxacin MTS QC Results Organism Concentration (µg/mL) Reference MTS E. coli ATCC 25922 Expected Result: 0.008-0.03 µg/mL 0.004 0.008 4 0.015 47 42 0.03 14 15 0.06 P. aeruginosa ATCC 27853 Expected Result: 0.12-0.5 µg/mL 0.06 0.12 2 11 0.25 53 50 0.5 6 1 Inoculum Density Check: The inoculum was prepared to achieve turbidity equivalent to a 0.5 McFarland standard. Colony counts were performed periodically at each site for all QC replicates. Inoculum density checks were performed and the colony counts obtained for each QC strain were within the recommended range of approximately Regulation section: