VITEK® 2 AST-Gram Negative Tigeovcline is designed for antimicrobial susceptibility testing of Gram negative bacilli and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Negative Tigecycline is a quantitative test. Tigecycline has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumonia

In vitro data available but clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Serratia marcescens

The VITEK@2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococus spp., Enterococcus spp., and clinically significant yeast.

Device Description

The VITEK® 2 AST Cards are essentially miniaturized versions of the doubling dilution technique for determining the minimum inhibitory concentration (MIC) microdilution methodology.

The isolate to be tested is diluted to a standardized concentration in 0.45 - 0.50% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK® 2 automatically fills, seals and places the card into the incubator/reader. The VITEK® 2 Compact has a manual filling and sealing operation. The VITEK® 2 monitors the growth of each well in the card over a defined period of time (up to 18 hours). At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antimicrobial contained on the card.

AI/ML Overview

The VITEK 2 AST-GN Tigecycline device is an automated system for antimicrobial susceptibility testing of Gram-negative bacilli. The study assessed its performance against the CLSI broth microdilution reference method.

1. Acceptance Criteria and Reported Device Performance:

The primary performance metrics for this device are Essential Agreement (EA) and Category Agreement (CA) when compared to the CLSI broth microdilution reference method. The acceptance criteria are not explicitly stated as numerical targets in the provided text but are implied by the reported "acceptable performance."

Metric	Acceptance Criteria (Implied)	Reported Device Performance
Overall Essential Agreement	Acceptable Performance	98.9%
Overall Category Agreement	Acceptable Performance	98.6%
Reproducibility	Acceptable Results	Acceptable Results
Quality Control	Acceptable Results	Acceptable Results

2. Sample Size Used for the Test Set and Data Provenance:

The document states an "external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains." However, the specific numerical sample size for the test set is not provided in the given text.

The data provenance is from an "external evaluation," and it involved "clinical isolates" and "challenge strains," suggesting a mix of retrospective (stock clinical isolates, challenge strains) and potentially prospective (fresh clinical isolates) data. The country of origin of the data is not specified.

3. Number of Experts and Qualifications for Ground Truth:

The document mentions that the performance of the VITEK 2 AST-GN Tigecycline was compared with the CLSI broth microdilution reference method. This method itself serves as the 'ground truth.' It is a standardized laboratory procedure, not typically established by individual experts but rather by a consensus of scientific and medical professionals who develop the CLSI (Clinical and Laboratory Standards Institute) guidelines. Therefore, the concept of "number of experts used to establish the ground truth" in the traditional sense of expert consensus on images or diagnoses does not apply here. The ground truth is the result produced by the CLSI reference method.

4. Adjudication Method:

Since the ground truth is established by a standardized laboratory reference method (CLSI broth microdilution), there is no adjudication method described or necessary in the typical sense (e.g., 2+1, 3+1). The VITEK 2 results are directly compared to the output of the reference method.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an automated system for susceptibility testing, not an imaging or diagnostic device that requires human interpretation. Therefore, there is no "human readers improve with AI vs without AI assistance" component.

6. Standalone Performance:

Yes, a standalone performance evaluation was done. The study directly compared the performance of the algorithm only (VITEK 2 AST-GN Tigecycline system) to the CLSI broth microdilution reference method. The reported Essential Agreement and Category Agreement percentages represent the device's standalone performance.

7. Type of Ground Truth Used:

The ground truth used was the CLSI broth microdilution reference method, which is a standardized and widely accepted laboratory procedure for determining antimicrobial minimum inhibitory concentrations (MICs).

8. Sample Size for the Training Set:

The document does not specify the sample size used for the training set. It only describes the "external evaluation" for performance assessment.

9. How the Ground Truth for the Training Set Was Established:

The document does not provide information on how the ground truth for any potential training set was established. Given the nature of an automated system, it is likely that internal development and validation would involve similar reference methods to establish ground truth for training, but this is not explicitly stated.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

January 24, 2017

BIOMÉRIEUX, INC. JENNIFER JINES REGULATORY AFFAIRS SPECIALIST 595 ANGLUM RD. HAZELWOOD MO 63042

Re: K163006

Trade/Device Name: VITEK 2 AST-GN Tigecvcline (<0.5->8 ug/mL) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully automated short-term incubation cycle antimicrobial susceptibility system Regulatory Class: II Product Code: LON, LTW, LTT Dated: October 26, 2016

Received: October 28, 2016

Dear Ms. Jines:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Ribhi Shawar -A

For Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K163006

Device Name VITEK® 2 AST-GN Tigecycline (≤0.5 ->8 µg/mL)

Indications for Use (Describe)

Active in vitro and in clinical infections: Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumonia

In vitro data available but clinical significance is unknown: Citrobacter koseri Enterobacter aerogenes Serratia marcescens

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) SUMMARY

VITEK® 2 AST-GN Tigecycline

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Jennifer JinesRegulatory Affairs Specialist
Phone Number:	314-731-8352
Fax Number:	314-731-8689
Date of Preparation:	October 26, 2016
B. Device Name:
Formal/Trade Name:	VITEK® 2 AST- GN Tigecycline (≤0.5 - ≥8µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code LON
Common Name:	VITEK® 2 AST-GN Tigecycline
C. Predicate Device:	VITEK® 2 AST-GN Cefepime (K161227)

D. 510(k) Summary:

VITEK® 2 AST-Gram Negative Tigecycline is designed for antimicrobial susceptibility testing of Gram negative bacilli and is intended for use with the VITEK® 2 and VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Negative Tigecycline is a quantitative test. Tigecycline has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

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Active in vitro and in clinical infections

Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumonia

In vitro data available but clinical significance is unknown Citrobacter koseri Enterobacter aerogenes Serratia marcescens

The VITEK® 2 Antimicrobial Susceptibility Test (AST) is intended to be used with the VITEK® 2 Systems for the automated quantitative or qualitative susceptibility testing of isolated colonies for the most clinically significant aerobic gram-negative bacilli, Staphylococcus spp., Enterococcus spp., Streptococcus spp. and clinically significant veast.

The antimicrobial presented in VITEK® 2 AST-GN Cards is in concentrations equivalent by efficacy to standard method concentrations in mcg/ml. The VITEK® 2 AST Cards are essentially miniaturized versions of the doubling dilution technique for determining the minimum inhibitory concentration (MIC) microdilution methodology.

VITEK® 2 AST-GN Tigecycline demonstrated substantially equivalent performance when compared with the CLSI broth microdilution reference method, as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009).

The Premarket Notification [510(k)] presents data in support of VITEK® 2 AST-GN Tigecycline. An external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The external evaluations were designed to confirm the acceptability of VITEK® 2 AST-GN Tigecycline by comparing its performance with the CLSI broth microdilution reference method incubated at 16-20 hrs. The data is representative of

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performance on both the VITEK®2 and VITEK® 2 Compact instrument platforms. VITEK® 2 AST-GN Tigecycline demonstrated acceptable performance of 98.9% overall Essential Agreement and 98.6% overall Category Agreement with the reference method. Reproducibility and Quality Control demonstrated acceptable results.

Regulation Number and Section

§ 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system.

(a)
Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system is a device that incorporates concentrations of antimicrobial agents into a system for the purpose of determining in vitro susceptibility of bacterial pathogens isolated from clinical specimens. Test results obtained from short-term (less than 16 hours) incubation are used to determine the antimicrobial agent of choice to treat bacterial diseases.(b)
Classification. Class II (special controls). The special control for this device is FDA's guidance document entitled “Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA.”