VITEK® 2 Gram Positive Tigecycline is designed for antimicrobial susceptibility testing of Gram positive microorganisms 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 Gram Positive Tigecycline is a qualitative test. Tigecycline has been shown to be active against the organisms listed below according to the FDA label for the antimicrobial.

Active in vitro and in clinical infections:

Enterococcus faecalis (Vancomycin-susceptible isolates only) Staphylococcus aureus (methicillin-susceptible and -resistant isolates) Streptococcus agalactiae

Active in vitro but their clinical significance is unknown: Enterococcus faecium (Vancomycin susceptible and resistant isolates) Staphylococcus epidermidis Staphylococcus haemolyticus Enterococcus casseliflavus.

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

Device Description

The antimicrobial presented in VITEK 2 AST 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.

The bacterial isolate to be tested is diluted to a standardized concentration in 0.45% saline before being used to rehydrate the antimicrobial medium within the card. The VITEK 2 System 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 MC value along with the interpretive category result for each antibiotic contained on the card.

AI/ML Overview

This document describes the VITEK® 2 Gram Positive Tigecycline device, which is an automated system for antimicrobial susceptibility testing of Gram-positive microorganisms.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Defined by FDA Class II Special Controls Guidance Document)	Reported Device Performance (VITEK® 2 Gram Positive Tigecycline)
Substantial equivalence to CLSI broth microdilution reference method	99.4% overall Category Agreement with CLSI broth microdilution reference method
Acceptable Reproducibility	Demonstrated acceptable results
Acceptable Quality Control	Demonstrated acceptable results

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

Sample Size: Not explicitly stated as a numerical value for the test set but implies a collection of isolates. The document refers to "fresh and stock clinical isolates and stock challenge strains."
Data Provenance: The study involved an "external evaluation" using "fresh and stock clinical isolates and stock challenge strains." This suggests a combination of retrospective (stock isolates/strains) and potentially prospective (fresh clinical isolates) data. The country of origin is not specified, but the submission is to the US FDA, implying relevance to a US context or similar regulatory standards.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The document does not mention the number of experts or their qualifications for establishing the ground truth.
The ground truth was established by the CLSI broth microdilution reference method, which is a standardized laboratory procedure, not typically an expert consensus per se.

4. Adjudication Method for the Test Set

There is no mention of an adjudication method (such as 2+1 or 3+1) for the test set. The comparison was directly against the CLSI broth microdilution reference method.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve With AI vs. Without AI Assistance?

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted.
This device is an automated system for antimicrobial susceptibility testing which determines MIC values and interpretive categories. It does not involve human readers interpreting images or data where AI assistance would directly improve human performance in the same way as, for example, diagnostic imaging. The "AI" here is the automated system itself.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone performance evaluation was done. The VITEK® 2 system is an automated device designed to perform antimicrobial susceptibility testing "without human-in-the-loop performance" during the measurement and interpretation stages of the test itself. The evaluation compared the device's results directly to the CLSI reference method.

7. The Type of Ground Truth Used

The ground truth used was the CLSI broth microdilution reference method. This is a well-established, standardized laboratory method for determining minimum inhibitory concentrations (MICs) of antimicrobials.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" or its sample size. This type of device, an automated AST system, is typically developed and validated against a large number of known isolates and reference methods rather than trained anew on a specific dataset in the way a machine learning algorithm might be. The reported performance refers to the external evaluation data, which serves as a validation set.

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

Since a distinct "training set" is not mentioned, the method for establishing its ground truth is not provided. For the validation/external evaluation set, the ground truth was established by the CLSI broth microdilution reference method. This method involves preparing serial dilutions of the antimicrobial agent and inoculating them with a standardized bacterial suspension to determine the lowest concentration that inhibits visible bacterial growth (MIC).

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows the logo for bioMerieux on the left side of the image. To the right of the logo is the number K072695. The logo consists of a circle with lines inside of it and the name of the company below it. The number is handwritten and appears to be a serial number.

510(k) SUMMARY

VITEK® 2 Gram Positive Tigecycline

N 1 6 2007

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Jolyn TenlladoSenior Regulatory Affairs Specialist
Phone Number:	314-731-8386
Fax Number:	314-731-8689
Date of Preparation:	September 20, 2007
B. Device Name:
Formal/Trade Name:	VITEK® 2 Gram Positive Tigecycline ( $≤$ 0.12 - $≥$ 2 µg/ml)
Classification Name:	Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility Device, 21 CFR 866.1645
Common Name:	VITEK 2 AST-GP Tigecycline
C. Predicate Device:	VITEK 2 Gram Positive Daptomycin (K050075).

D. 510(k) Summary:

B. D

Active in vitro and in clinical infections: Enterococcus faecalis (Vancomycin-susceptible isolates only) Staphylococcus aureus (methicillin-susceptible and -resistant isolates) Streptococcus agalactiae

The antimicrobial presented in VITEK 2 AST Cards is in concentrations equivalent by efficacy to standard method concentrations in mcg/ml. The VITEK 2 AST Cards are essentially miniaturized

bioMérieux, Inc.

595 Anglum Road, Hazelwood, Missouri 63042-2320, USA Phone: 314/731-8500 800/638-4835 Fax: 314/731-8700

{1}------------------------------------------------

versions of the doubling dilution technique for determining the minimum inhibitory concentration (MIC) microdilution methodology.

VITEK 2 Gram Positive 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 Feb. 5, 2003.*

The Premarket Notification (510[k]) presents data in support of VITEK 2 Gram Positive Tigecycline. An external evaluation was conducted with fresh and stock clinical isolates and stock challenge strains. The external evaluations were designed to confirm the acceptability of VITEK 2 Gram Positive Tigecycline by comparing its performance with the CLSI broth microdilution reference method. The data is representative of performance on both the VITEK 2 and VITEK 2 Compact instrument platforms, as evidenced in the AST equivalency study presented in the VITEK 2 Compact 510(k), K050002. VITEK 2 Gram Positive Tigecycline demonstrated acceptable performance of 99.4% overall Category Agreement. Reproducibility and Quality Control demonstrated acceptable results.

*Note: This device clinical trial was initiated prior to the March 5, 2007 issuance of the revised guidance, which is why the older quidance document is cited.

{2}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/2/Picture/2 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a stylized eagle with three lines representing its wings. The eagle is facing right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" is arranged in a circular pattern around the eagle.

NOV 1 6 2007

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Jolyn Tellando Senior Regulatory Affairs Specialist bioMérieux, Inc. 595 Anglum Road Hazelwood, MO 63042

Re: K072695

Trade/Device Name: VITEK® 2 Gram Positive Tigecycline (≤ 0.12 -> 2 µg/ml) Regulation Number: 21 CFR 866.1645 Regulation Name: Short term Antimicrobial Susceptibility Test Regulatory Class: Class II Product Code: LON Dated: September 20, 2007 Received: September 24, 2007

Dear Ms. Tellando:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{3}------------------------------------------------

Page 2 –

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Sally attaym

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{4}------------------------------------------------

Indications for Use

510(k) Number (if known): K072695

Device Name: VITEK® 2 Gram Positive Tigecycline (< 0.12 - > 2 µg/ml)

Indications For Use:

Active in vitro and in clinical infections:

Enterococcus faecalis (Vancomycin-susceptible isolates only) Staphylococcus aureus (methicillin-susceptible and -resistant isolates) Streptococcus agalactiae

Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concerrence of CORH, Office of In Vitro Diagnostic Devices (OIVD) Fleddle est

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of 1

510(k) K072695

K072695, Amended p. 9

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.”