VITEK® 2 AST-Gram Negative Cefazolin 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 Cefazolin is a quantitative test. Cefazolin 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: Escherichia coli Proteus mirabilis

The VITEK® 2 Gram-Negative Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of clinically significant aerobic Gram-negative bacilli to antimicrobial agents when used as instructed.

Device Description

The principle of the VITEK® 2 AST cards is based on the microdilution minimum inhibitory concentration (MIC) technique reported by MacLowry and Marsh() and Gerlach(0). The VITEK® 2 AST card is essentially a miniaturized, abbreviated and automated version of the doubling dilution technique(3).

Each VITEK® 2 AST card contains 64 wells. A control well which only contains microbiological culture media is resident on all cards. The remaining wells contain premeasured portions of a specific antibiotic combined with culture media. The bacterial or yeast isolate to be tested is diluted to a standardized concentration with 0.45 - 0.5% 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, sealing and loading operation. The VITEK® 2 Systems monitor the growth of each well in the card over a defined period of time. At the completion of the incubation cycle, a report is generated that contains the MIC value along with the interpretive category result for each antibiotic contained on the card.

VITEK® 2 AST-GN Cefazolin (≤1 - ≥32 µg/mL) has the following concentrations in the card: 1, 2, and 8 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

AI/ML Overview

The provided text describes the performance study for the VITEK® 2 AST-Gram Negative Cefazolin (≤1 - ≥32 µg/mL) device, which is an antimicrobial susceptibility testing system.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance:

The acceptance criteria for AST systems are defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA (Issued August 28, 2009). While the specific numerical thresholds for acceptance are not explicitly listed in this document extract, the performance data provided is presented against these guidelines.

Metric	Acceptance Criteria (Implicit from FDA Guidance)	Reported Performance (Cefazolin)
Essential Agreement (EA) %	High agreement with reference method. Deviations (VME, mE, ME) within acceptable limits.	97.4% EA
Very Major Errors (VME)	Low (e.g., typically < 1.5%)	N/A (reported as 0.8% in Category Agreement)
Major Errors (ME)	Low (e.g., typically < 3%)	N/A (reported as 1.3% in Category Agreement)
Minor Errors (mE)	Low (e.g., typically < 7%)	N/A (reported as 15.6% in Category Agreement)
Category Agreement (CA) %	High agreement with reference method. Deviations (VME, mE, ME) within acceptable limits.	83.6% CA
Reproducibility %	High (e.g., typically > 95%)	100% Reproducibility

Note: The "N/A" for VME, ME, and mE under Essential Agreement indicates that these specific error types are separately reported under Category Agreement in the provided table, which is a common practice for AST system performance reporting.

2. Sample Size and Data Provenance:

Test Set Sample Size: Not explicitly stated as a single number. The study mentions "fresh and stock clinical isolates, as well as a set of challenge strains." The quantitative performance metrics (EA, CA, Reproducibility) are derived from this test set.
Data Provenance: The document does not specify the country of origin of the data. It indicates the study was an "external evaluation." It is implied to be prospective as it involves testing isolates with the VITEK® 2 AST-GN Cefazolin device and comparing it to a reference method.

3. Number of Experts and Qualifications:

Not applicable. This study evaluated an automated antimicrobial susceptibility test system (VITEK® 2) against a recognized reference method (CLSI broth microdilution). It did not involve human experts establishing ground truth through image interpretation or similar processes common in AI/Imaging studies.

4. Adjudication Method for the Test Set:

Not applicable. Ground truth for antimicrobial susceptibility testing is established by a standardized laboratory reference method (CLSI broth microdilution), not by consensus among human experts.

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

No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for AI systems that assist human readers in tasks like image interpretation. The VITEK® 2 system is an automated diagnostic device; its performance is compared to a laboratory reference standard, not to human readers' performance with and without AI assistance.

6. Standalone Performance:

Yes, a standalone performance evaluation was done. The reported performance metrics (Essential Agreement, Category Agreement, Reproducibility) represent the performance of the VITEK® 2 AST-GN Cefazolin system (algorithm only, as it's an automated test) compared to the CLSI broth microdilution reference method.

7. Type of Ground Truth Used:

The type of ground truth used was CLSI broth microdilution reference method, incubated at 16-24 hours. This is a widely accepted laboratory standard for determining antimicrobial susceptibility.

8. Sample Size for the Training Set:

Not applicable or not explicitly mentioned as a "training set" in the context of machine learning. This device is described as operating based on "microdilution minimum inhibitory concentration (MIC) technique," which suggests a deterministic algorithm rather than a machine learning model that undergoes "training." The system's rules or parameters would be pre-defined based on established microbiological principles, not trained on a large dataset in the way a deep learning model would be.

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

Not applicable for the reasons mentioned above (not a machine learning model with a distinct training phase requiring ground truth establishment from raw data). The "ground truth" equivalent for developing such a system would involve extensive research and validation against established microbiological methods like the CLSI broth microdilution method during its initial development and calibration.

Summary

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February 9, 2023

bioMérieux, Inc. Kyle Olney Regulatory Affairs Specialist 595 Anglum Rd. Hazelwood, Missouri 63042

Re: K222073

Trade/Device Name: Vitek 2 AST Gram Negative Cefazolin (≤1 - ≥32 µg/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 Dated: July 12, 2022 Received: July 14, 2022

Dear Kyle Olney:

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 mediation-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 -S

Ribhi Shawar, Ph.D. (ABMM) Branch Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics 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) K222073

Device Name

VITEK® 2 AST-Gram Negative Cefazolin (≤1 - ≥32 µg/mL)

Indications for Use (Describe)

Active in vitro and in clinical infections: Escherichia coli Proteus mirabilis

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-Gram Negative Cefazolin (≤1 - ≥32 µg/mL)

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Kyle OlneyRegulatory Affairs Specialist
Phone Number:	314 -805-8642
Fax Number:	314-731-8689
Date of Preparation:	June 24, 2022
Device Name:
Formal/Trade Name:	VITEK® 2 AST-Gram Negative Cefazolin (≤1 - ≥32µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON
Common Name:	VITEK® 2 AST-GN Ciprofloxacin (≤1 - ≥32 µg/mL)
Predicate Device:	VITEK® 2 AST-GN Omadacycline (≤0.25 - ≥16 µg/mL)(K213931)

D. Device Description:

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VITEK® 2 AST-GN Cefazolin (≤1 - ≥32 µg/mL) has the following concentrations in the card: 1, 2, and 8 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

E. Substantial Equivalence Information:

The similarities and differences of the VITEK® 2 AST-GN Cefazolin (≤1 - ≥32 µg/mL) when compared to the predicate device, VITEK® 2 AST-GN Omadacycline (≤0.25 ->16 µg/mL), are described in the Table 1 below.

Item	Device:VITEK® 2 AST-Gram NegativeCefazolin(≤1 - ≥32 µg/mL)	Predicate:VITEK® 2 AST-Gram NegativeOmadacycline (≤0.25 - ≥16 µg/mL)(K213931)
Similarities
Intended Use	VITEK® 2 AST-Gram NegativeCefazolin is designed forantimicrobial susceptibility testing ofGram negative bacilli and is intendedfor use with the VITEK® 2 andVITEK® 2 Compact Systems as alaboratory aid in the determination ofin vitro susceptibility toantimicrobial agents. VITEK® 2AST-Gram Negative Cefazolin is aquantitative test.The VITEK® 2 Gram-NegativeSusceptibility Card is intended foruse with the VITEK® 2 Systems inclinical laboratories as an in vitrotest to determine the susceptibility of	VITEK® 2 AST-Gram NegativeOmadacycline is designed forantimicrobial susceptibility testingof Gram negative bacilli and isintended for use with the VITEK®2 and VITEK® 2 Compact Systemsas a laboratory aid in thedetermination of in vitrosusceptibility to antimicrobialagents. VITEK® 2 AST-GramNegative Omadacycline is aquantitative test.The VITEK® 2 Gram-NegativeSusceptibility Card is intended foruse with the VITEK® 2 Systems inclinical laboratories as an in vitro

Table 1: Substantial Equivalence

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	clinically significant aerobic Gramnegative bacilli to antimicrobialagents when used as instructed.	test to determine the susceptibilityof clinically significant aerobicGram negative bacilli toantimicrobial agents when used asinstructed.
Test Methodology	Automated quantitativeantimicrobial susceptibility test foruse with the VITEK® 2 and VITEK®2 Compact Systems to determine thein vitro susceptibility ofmicroorganisms	Same
Inoculum	Saline suspension of organism	Same
Test Card	Gram Negative (AST-GN)Susceptibility Card	Same
Instrument	VITEK® 2 and VITEK® 2 CompactSystems	Same
Type of Test	VITEK® 2 AST-Gram NegativeCefazolin is a quantitative test.	Same
Differences
AntimicrobialAgent	Cefazolin	Omadacycline
Concentrations	1, 2, 8	0.5, 2, 8, 16
Indications for use	Cefazolin has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label for thisantimicrobial.	Omadacycline has been shown tobe active against most strains ofthe microorganisms listed below,according to the FDA label for thisantimicrobial.
	Active in vitro and in clinicalinfections:Escherichia coliProteus mirabilis	Active in vitro and in clinicalinfections:For ABSSSI:Enterobacter cloacaeKlebsiella pneumoniaeFor CABP:Klebsiella pneumoniae

F. Intended Use:

VITEK® 2 AST-Gram Negative Cefazolin 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 Cefazolin in is a quantitative test. Cefazolin has been shown to

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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:

Gram-Negative Bacteria: Escherichia coli Proteus mirabilis

G. Performance Overview and Conclusion:

VITEK® 2 AST-GN Cefazolin 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 Cefazolin. 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 Cefazolin by comparing its performance with the CLSI broth microdilution reference method incubated at 16-24 hrs. The data is representative of performance on both the VITEK® 2 Compact instrument platforms.

The VITEK® 2 AST-GN Cefazolin demonstrated acceptable performance as presented in Table 2 below:

Antimicrobial	Antimicrobial Code	Antibiotic Version	Bp1	Comment2	Essential Agreement% Error				Category Agreement% Error				% Reproducibility
					% EA	VME	ME	mE	% CA	VME	ME	mE
Cefazolin	CZ	cz05n	CLSI(FDA)	#, EEnterobacteriaceae	97.4	N/A	N/A	N/A	83.6	0.8	1.3	15.6	100

Table 2: VITEK® 2 AST-GN Cefazolin Performance

Reproducibility and Quality Control demonstrated acceptable results.

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H. References:

1. MacLowry, J.D. and Marsh, H.H., Semi-automatic Microtechnique for Serial Dilution Antibiotic Sensitivity Testing in the Clinical laboratory, Journal of Laboratory Clinical Medicine, 72:685-687, 1968.
1. Gerlach, E.H., Microdilution 1: A Comparative Study, p. 63-76. Current Techniques for Antibiotic Susceptibility Testing. A. Balows (ed.), Charles C. Thomas, Springfield, IL, 1974.
1. Barry, A.L., The Antimicrobic Susceptibility Test, Principles and Practices, Lea and Febiger, Philadelphia, PA, 1976.

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.”