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 cvcle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

AI/ML Overview

This document describes the regulatory submission for the VITEK® 2 Gram Negative Piperacillin/Tazobactam system, specifically a Special 510(k) for a device modification related to updated breakpoints for Pseudomonas aeruginosa. The provided text details the device's intended use and performance without explicitly laying out acceptance criteria in a table format common for AI/ML device clearances. However, by analyzing the "Special 510(k) Summary" section, we can infer the acceptance criteria and performance as presented for this specific modification.

Here's a breakdown of the requested information based on the provided text:

1. A table of acceptance criteria and the reported device performance

Based on the information provided, the primary performance metric reported for this modification is Category Agreement.

Acceptance Criteria	Reported Device Performance
Overall acceptable performance of 92.3% Category Agreement based on FDA Class II Special Controls Guidance Document for AST Systems.	92.3% Category Agreement

Note: The document specifies that the performance is evaluated against 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. This guidance outlines the specific criteria for Category Agreement (CA), Essential Agreement (EA), and overall acceptable performance for AST systems.

2. Sample size used for the test set and the data provenance

The document does not explicitly state the sample size (number of isolates) used for the test set. It mentions that "The data are representative of performance on both the VITEK 2 and VITEK 2 COMPACT instrument platforms." No specific information about the country of origin or whether the data was retrospective or prospective is provided. The focus of this specific submission is on the re-evaluation of performance due to a breakpoint change for a single organism (Pseudomonas aeruginosa).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The ground truth is established by the CLSI broth microdilution reference method. This is a standardized laboratory method for determining antimicrobial susceptibility, not typically requiring expert human interpretation beyond standard laboratory procedures and quality control. Therefore, the concept of "experts" in the context of ground truth establishment, as it applies to AI/ML devices requiring human labeling, is not relevant here.

4. Adjudication method for the test set

Not applicable. The ground truth is a laboratory reference method (CLSI broth microdilution), not a subjective human interpretation requiring adjudication.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done

Not applicable. This is an antimicrobial susceptibility test system, not an imaging device requiring human reader interpretation or AI-assistance for diagnosis. The device generates MIC values and interpretive categories (Susceptible, Intermediate, Resistant).

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

The VITEK 2 system automatically performs the test and generates results. The reported performance (92.3% Category Agreement) is the standalone performance of the device against the reference method. There isn't a "human-in-the-loop" component in the direct interpretation of the raw data from the device to produce the MIC and categorical result.

7. The type of ground truth used

The ground truth used is the CLSI broth microdilution reference method. This is a gold-standard laboratory method for determining minimum inhibitory concentrations (MICs) of antimicrobials, which then dictate the interpretive category (susceptible, intermediate, resistant).

8. The sample size for the training set

The document does not provide details on a distinct "training set" or its sample size. The VITEK 2 system operates based on established principles of growth detection and comparison to provide MICs. The original development and "training" (calibration) would have been part of the predicate device's clearance (K113200). This submission is a modification to update the interpretation when a new breakpoint for a specific organism is applied, not a new AI model requiring a separate training phase.

9. How the ground truth for the training set was established

As in point 8, the concept of a "training set" for an AI/ML model is not directly applicable in the same way for this type of device. The original calibration and validation of the VITEK 2 system, which would serve a similar purpose to "training," would have established its internal algorithms and growth detection parameters. This would have involved extensive testing against the CLSI broth microdilution reference method with a large collection of isolates. The current modification focuses on applying a new interpretive breakpoint, not retraining the core measurement algorithm.

Summary

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August 30, 2021

bioMérieux, Inc Mary Beth Anheuser Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri 63042 USA

Re: K211630

Trade/Device Name: VITEK 2 AST-Gram Negative Piperacillin / Tazobactam (<4 ≥128 ug/mL) Regulation Number: 21 CFR 866.1645 Regulation Name: Fully Automated Short-Term Incubation Cycle Antimicrobial Susceptibility System Regulatory Class: Class II Product Code: LON, LTW, LTT Dated: May 25, 2021 Received: May 27, 2021

Dear Mary Beth Anheuser:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Ribhi Shawar, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

Device Name

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
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Prescription Use (Part 21 CFR 801 Subpart D)

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

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Special 510(k) SUMMARY

VITEK ®2 Gram Negative Piperacillin/Tazobactam Special 510(k): Device Modification

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Mary Beth AnheuserStaff, Regulatory Affairs Specialist
Phone Number:	618-667-3179
Fax Number:	314-731-8689
Date of Preparation:	May 25, 2021
Formal/Trade Name:	VITEK® 2 Gram Negative Piperacillin/Tazobactam(≤4 - ≥128 µg/mL)
Classification Name:	Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility Device, 21 CFR 866.1645
Common Name:	VITEK 2 AST-GN Piperacillin/Tazobactam
Predicate Device:	VITEK 2 AST-GN Piperacillin/Tazobactam (K113200)

D. 510(k) Summary:

VITEK®2 Gram Negative Piperacillin/Tazobactam is designed for antimicrobial susceptibility testing of Acinetobacter baumanii. Escherichia coli. Klebsiella pneumoniae. Pseudomonas aeruginosa, Citrobacter koseri, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, and Salmonella enterica. It 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. 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

bioMérieux, Inc.

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

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the incubation cvcle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

VITEK 2 Gram Neqative Piperacillin/Tazobactam 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.

This submission is the result of a FDA 2019 breakpoint change, as published on the FDA STIC website, for Pseudomonas aeruginosa tested with Piperacillin/Tazobactam (≤16, 32-64, 128 ≥). The intended use of the VITEK 2 Gram Negative Piperacillin/Tazobactam, as described in the labeling (package insert), has not changed as a result of this modification to the breakpoints specific to Pseudomonas aeruginosa. The overall performance of the device has been updated to reflect the performance of Pseudomonas aeruginosa when the updated breakpoints are applied. This modification does not affect the fundamental scientific technology of this device.

This premarket Notification (510(k)) presents the data in support of the VITEK 2 Gram Negative Piperacillin/Tazobactam test when the updated breakpoints for Pseudomonas aeruginosa (≤16, 32-64, 128 ≥) are applied. The data are representative of performance on both the VITEK 2 and VITEK 2 COMPACT instrument platforms. VITEK 2 Gram Negative Piperacillin/Tazobactam demonstrated an overall acceptable performance of 92.3% Category Agreement. Quality control and reproducibility are acceptable and remain unchanged from the original clearance (K113200).

The VITEK 2 Gram Neqative Piperacillin/Tazobactam test demonstrated acceptable performance during verification of the breakpoint change specific to Pseudomonas aeruginosa. No new risks were introduced through this modification and the performance equivalency has been established through verification testing. This allows for a substantial equivalence decision when compared to the current device cleared under K113200.

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.”