VITEK® 2 Gram Negative Ceftazidime/Avibactam 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 Gram Negative Ceftazidime/ Avibactam is a quantitative test. Ceftazidime/Avibactam has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active both in vitro and in clinical infections:

Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

The following in vitro data are available, but clinical significance is unknown:

Citrobacter koseri Enterobacter aerogenes Morganella morganii Providencia stuartii 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., Streptococcus spp., Streptococcus 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

Here's a breakdown of the acceptance criteria and study details for the VITEK® 2 AST-GN Ceftazidime/Avibactam device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Target)	Reported Device Performance (%)
Essential Agreement (EA)	94.5%
Category Agreement (CA)	98.7%
Major Error Rate	1.4% (Overall)
Adjusted Major Error Rate	0.5% (Adjusted for 9 errors within EA)
Reproducibility	Acceptable results
Quality Control	Acceptable results

Note: The specific numerical targets for Essential Agreement, Category Agreement, and Major Error Rate are not explicitly stated as "acceptance criteria" percentages in the document, but rather "acceptable performance" is implied by the reported percentages, which are compared against general guidance for AST systems. The document states that the device "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)." This suggests compliance with the performance metrics outlined in that guidance.

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

Sample Size:
- The document implies a sample size for the major error rate calculation: 998 strains.
- It mentions "fresh and stock clinical isolates, as well as a set of challenge strains." The exact total number of isolates tested for overall performance (EA and CA) is not explicitly stated, but based on the major error calculation for 998 strains, it's at least that number or more for the full evaluation.
Data Provenance: Not explicitly stated (e.g., specific countries). However, the use of "clinical isolates" suggests a real-world collection, and "challenge strains" implies some curated, potentially reference or difficult-to-test strains. The study is retrospective in the sense that these are collected isolates being tested.

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

This information is not provided in the document. The ground truth is established by the CLSI broth microdilution reference method, which is a standardized laboratory procedure, not an expert panel.

4. Adjudication Method for the Test Set

This information is not applicable as the ground truth is established by the CLSI broth microdilution reference method, not through expert consensus requiring adjudication. The major error rate calculation describes an adjustment based on how close the errors were to the reference method (within one dilution), but this is a statistical adjustment, not an expert adjudication process.

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, an MRMC comparative effectiveness study involving human readers and AI assistance was not done.
This device is an automated antimicrobial susceptibility testing (AST) system. Its purpose is to automate the determination of susceptibility, not to assist human readers in interpreting images or other data. The "readers" here are the VITEK® 2 systems themselves, interpreting growth in wells.

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

Yes, this was a standalone performance study of the VITEK® 2 AST-GN Ceftazidime/Avibactam system.
The system is the algorithm (or rather, the automated process) that determines susceptibility based on growth patterns in the card wells. Its performance was compared directly against the reference method without human intervention in the interpretation process of the device results.

7. The Type of Ground Truth Used

The ground truth used was the CLSI broth microdilution reference method. This is a laboratory-established standard for determining minimum inhibitory concentrations (MICs) of antimicrobial agents.

8. The Sample Size for the Training Set

The document does not provide a sample size for a training set. This is because the VITEK® 2 system, while automated, is likely based on established principles of growth detection and does not typically involve a "training set" in the machine learning sense to learn a new classification model during development for each new antimicrobial/organism combination. Instead, performance is validated against a reference method.

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

As there's no explicit training set in the machine learning sense mentioned, this question is not applicable. The ground truth for the validation or test set was established by the CLSI broth microdilution reference method.

Summary

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

Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

December 19, 2017

bioMerieux, Inc. Ms. Cherece Jones Staff Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri 63042

Re: K172944

Trade/Device Name: VITEK 2 AST-GN Ceftazidime/Avibactam (<0.12 ->16 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: September 25, 2017 Received: September 26, 2017

Dear Ms. Cherece Jones:

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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

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

Part 820); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/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 -S 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

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

Indications for Use

510(k) Number (if known) K172944

Device Name

VITEK® 2 AST-GN Ceftazidime/Avibactam (≤0.12 ->16 µg/mL)

Indications for Use (Describe)

Active both in vitro and in clinical infections:

Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

The following in vitro data are available, but clinical significance is unknown:

Citrobacter koseri Enterobacter aerogenes Morganella morganii Providencia stuartii Serratia marcescens

Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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

Image /page/4/Picture/0 description: The image shows the logo for bioMérieux. The logo consists of a stylized globe with horizontal lines on the left side and a solid black fill on the right side. A curved line extends from the top of the globe, arcing over it. Below the globe is the company name, "BIOMÉRIEUX," in a sans-serif font.

510(k) SUMMARY

VITEK® 2 AST-GN Ceftazidime/Avibactam

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Cherece L. JonesStaff Regulatory Affairs Specialist
Phone Number:	314-731-8684
Fax Number:	314-731-8689
Date of Preparation:	September 25, 2017
B. Device Name:
Formal/Trade Name:	VITEK® 2 AST-GN Ceftazidime/Avibactam (≤0.12 - ≥ 16 µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON
Common Name:	VITEK® 2 AST-GN Ceftazidime/Avibactam
C. Predicate Device:
	VITEK® 2 AST-GN Ceftolozane/Tazobactam (≤0.25 - ≥ 32 ug/ml) (K161510)

D. 510(k) Summary:

VITEK® 2 Gram Negative Ceftazidime/Avibactam 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 Gram Negative Ceftazidime/Avibactam is a quantitative test. Ceftazidime/Avibactam has been shown to be active against most strains of the microorganisms listed below, according to the FDA label for this antimicrobial.

Active both in vitro and in clinical infections:

{5}------------------------------------------------

Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa

The following in vitro data are available, but clinical significance is unknown:

Citrobacter koseri Enterobacter aerogenes Morganella morganii Providencia stuartii 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 yeast.

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 Ceftazidime/Avibactam 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 Ceftazidime/Avibactam. 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

{6}------------------------------------------------

the acceptability of VITEK® 2 AST-GN Ceftazidime/Avibactam by comparing its performance with the CLSI broth microdilution reference method incubated at 16-20 hrs. The data is representative of performance on both the VITEK® 2 Compact instrument platforms.

The VITEK® 2 AST-GN Ceftazidime/Avibactam (≤ 0.12 – ≥ 16 µg/mL) demonstrated acceptable performance as presented in Table 1 below:

Table 1: Performance Characteristics for VITEK® 2 AST-GN Ceftazidime/Avibactam (ڪ 0.12 – ≥ 16 µg/mL)

	% Essential Agreement	% Category Agreement*
	(EA)	(CA)
Overall Performance (with thereference method)	94.5	98.7

The overall categorical major error rate for Entervase and Pseudomonas 1.4% (14998). Nine (9) major errors were one dilution apart from the reference method and as such fall within essential agreement, and the lack of an intermediate breakpoint for Ceftazidime/Avibactam, the adjusted categorical major error rate is 0.5% (5/998).

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.”