VITEK® 2 AST-Gram Negative Eravacycline 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 Eravacycline is a quantitative test. Eravacycline 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 pneumoniae

In vitro data are available, but clinical significance is unknown:
Citrobacter koseri
Klebsiella (Enterobacter) aerogenes

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 (1) and Gerlach (2). 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 Eravacycline has the following concentrations in the card: 0.25, 1, 2 and 4 ug/mL (equivalent standard method concentration by efficacy in ug/mL).

AI/ML Overview

This document describes the validation of the VITEK® 2 AST-Gram Negative Eravacycline system for antimicrobial susceptibility testing.

Here's an analysis based on the provided text, addressing the points requested:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems: Guidance for Industry and FDA (Issued August 28, 2009)". This guidance document sets benchmarks for essential agreement and category agreement.

Acceptance Criteria (from FDA Guidance)	Reported Device Performance
Overall Essential Agreement: Acceptable performance	97.0%
Overall Category Agreement: Acceptable performance	99.1%

Note: While the document states "acceptable performance" for these metrics, it does not provide explicit numerical thresholds for acceptance within the text. However, the reported values are presented as meeting this acceptability.

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

The document states:

Test Set Description: "An external evaluation was conducted with fresh and stock clinical isolates, as well as a set of challenge strains."
Sample Size: The exact number of isolates/samples used in the external evaluation (test set) is not explicitly stated in the provided text.
Data Provenance: The document does not specify the country of origin for the data (clinical isolates). It also doesn't explicitly state whether the study was retrospective or prospective, though the use of "fresh and stock clinical isolates" suggests a mix, potentially involving prospectively collected fresh isolates and retrospectively accessed stock isolates.

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

This information is not provided in the document. The ground truth (reference method) for the VITEK® 2 system's performance is the CLSI broth microdilution reference method, which is a standardized laboratory procedure, not reliant on expert interpretation in the same way clinical image analysis might be. Therefore, the concept of "number of experts" or "qualifications of experts" establishing ground truth is not directly applicable here.

4. Adjudication Method for the Test Set

The concept of an "adjudication method" (like 2+1 or 3+1 for discrepancies) is typically relevant for studies where human interpretation of data (e.g., radiology images) forms the ground truth, and discrepancies between readers need to be resolved.

In this context, the ground truth is established by a standardized laboratory method (CLSI broth microdilution). Therefore, an adjudication method in the human-in-the-loop sense is not applicable and not mentioned in the document.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of Improvement with AI vs. without AI Assistance

This document describes the validation of an automated antimicrobial susceptibility testing (AST) system, not an AI-assisted diagnostic tool that humans use to interpret medical images or other complex data.

Therefore:

An MRMC comparative effectiveness study was not done as it's not relevant for this type of automated diagnostic device.
No effect size of human reader improvement with AI assistance is reported, as the system does not involve human readers interpreting AI outputs.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, this study effectively represents a standalone performance evaluation of the VITEK® 2 AST-Gram Negative Eravacycline system. The device itself is an automated system that provides a direct result (MIC value and interpretive category). Its performance is compared directly against the reference standard (CLSI broth microdilution method), without human intervention in the interpretation of the device's output.

7. The Type of Ground Truth Used

The type of ground truth used is the CLSI broth microdilution reference method. This is considered a gold standard laboratory method for determining antimicrobial susceptibility, providing quantitative Minimum Inhibitory Concentration (MIC) values.

8. The Sample Size for the Training Set

The document describes the "external evaluation" as the performance (test) set. It does not explicitly mention or provide the sample size for a training set. Automated AST systems like VITEK® 2 are typically developed using established microbiological principles and algorithmic analysis of growth patterns, rather than a machine learning approach that requires a distinct "training set" in the common sense of deep learning models. The "analysis algorithms" are described as "Growth Pattern Analysis" which suggests rule-based or statistical algorithms rather than trainable neural networks.

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

Since a distinct "training set" in the context of machine learning is not explicitly mentioned or implied to be used for a trainable algorithm, the method for establishing ground truth for such a set is not applicable/not provided. The system's underlying principles are based on established microbiology and the CLSI reference method serves as the benchmark for validation.

Summary

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August 5, 2019

bioMerieux, Inc. Esther Hernandez Regulatory Affairs Specialist 595 Anglum Road Hazelwood, Missouri 63042

Re: K191766

Trade/Device Name: VITEK 2 AST-Gram Negative Eravacycline (<=0.12 - >=4 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, LTW, LTT Dated: June 28, 2019 Received: July 1, 2019

Dear Esther Hernandez:

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

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) 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, Ph.D. Chief 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)

K191766

Device Name

VITEK® 2 AST-Gram Negative Eravacycline (≤ 0.12 - ≥ 4 µg/mL)

Indications for Use (Describe)

VITEK® 2 AST-Gram Negative Eravacycline is designed for antimicrobial susceptibility testing of Gram negative bacilli and is intended for use with the VITEK® 2 Compact Systems as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents. VITEK® 2 AST-Gram Negative in is a quantitative test. Eravacycline 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 pneumoniae

In vitro data are available, but clinical significance is unknown:

Citrobacter koseri Klebsiella (Enterobacter) aerogenes

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

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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Image /page/3/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo is a circle with the top half in dark blue and the bottom half in a gradient of yellow to green. The company name, "BIOMÉRIEUX", is written in white, sans-serif font in the center of the blue portion of the circle.

510(k) SUMMARY

VITEK® 2 AST-GN Eravacycline

A. 510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Esther HernandezRegulatory Affairs Specialist
Phone Number:	314-731-8841
Fax Number:	314-731-8689
Date of Preparation:	June 28, 2019
Device Name:
Formal/Trade Name:	VITEK® 2 AST- Gram Negative Eravacycline (≤$0.12 -\geq 4$ µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code LON
Common Name:	VITEK® 2 AST-GN Eravacycline
Predicate Device:	VITEK® 2 AST-GN Delafloxacin (K183524)

D. Device Description:

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

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Image /page/4/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo consists of a circle divided into two sections. The top section is a dark blue color and contains the company name "BIOMÉRIEUX" in white, sans-serif font. The bottom section is a gradient of yellow and green.

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 Eravacycline has the following concentrations in the card: 0.25, 1, 2 and 4 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 Eravacycline when compared to the predicate device, VITEK® 2 AST-GN Delafloxacin (K183524), are described in the following table.

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Image /page/5/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle with a blue upper half and a yellow-green lower half. The word "BIOMÉRIEUX" is written in white letters in the blue portion of the circle.

Item	Device:VITEK® 2 AST-GN Eravacycline	Predicate:VITEK® 2 AST-GN Delafloxacin(K183524)
	Similarities
Intended Use	VITEK® 2 AST-Gram NegativeEravacycline is designed forantimicrobial susceptibility testing ofGram negative bacilli and is intendedfor use with the VITEK® 2 and VITEK®2 Compact Systems as a laboratory aidin the determination of in vitrosusceptibility to antimicrobial agents.VITEK® 2 AST-Gram NegativeEravacycline is a quantitative test.Eravacycline has been shown to beactive against most strains of themicroorganisms listed below, accordingto the FDA label for this antimicrobial.Active in vitro and in clinical infections:Citrobacter freundiiEnterobacter cloacaeEscherichia coliKlebsiella oxytocaKlebsiella pneumoniae	VITEK 2 AST-Gram NegativeDelafloxacin is designed for antimicrobialsusceptibility testing of Gram negativebacilli and is intended for use with theVITEK 2 and VITEK 2 Compact Systemsas a laboratory aid in the determination ofin vitro susceptibility to antimicrobialagents. VITEK 2 AST-Gram NegativeDelafloxacin is a quantitative test.Delafloxacin has been shown to be activeagainst most strains of the microorganismslisted below, according to the FDA labelfor this antimicrobial.Active in vitro and in clinical infections:Escherichia coliEnterobacter cloacaeKlebsiella pneumoniaePseudomonas aeruginosa
	Klebsiella pneumoniaeIn vitro data are available, but clinicalsignificance is unknown:Citrobacter koseriKlebsiella (Enterobacter) aerogenesThe VITEK® 2 Gram-NegativeSusceptibility Card is intended for usewith the VITEK® 2 Systems in clinicallaboratories as an in vitro test todetermine the susceptibility of clinicallysignificant aerobic Gram-negativebacilli to antimicrobial agents whenused as instructed.	The VITEK 2 Gram-negative SusceptibilityCard is intended to for use with the VITEK 2Systems in clinical laboratories as an in vitrotest to determine the susceptibility ofclinically significant aerobic Gram-negativebacilli to antimicrobial agents when used asinstructed.

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Image /page/6/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle divided into two sections. The top section is a dark blue color and contains the word "BIOMÉRIEUX" in white, sans-serif font. The bottom section is a gradient of yellow and green.

Similarities Continued
TestMethodology	Automated quantitative antimicrobialsusceptibility test for use with theVITEK® 2 and VITEK® 2 CompactSystems to determine the in vitrosusceptibility of Gram negative bacilli	Same
Inoculum	Saline suspension of organism	Same
Test Card	VITEK®2 Gram Negative SusceptibilityTest Card	Same
Instrument	VITEK®2 and VITEK®2 CompactSystems	Same
AnalysisAlgorithms	Growth Pattern Analysis	Same
Differences
Antimi-crobialAgent	Eravacycline	Delafloxacin
Antimi-crobialConcen-trations	0.25, 1, 2, 4	0.06, 0.25, 0.5, 2

F. Intended Use:

VITEK® 2 AST-Gram Negative Eravacycline 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 Eravacycline is a quantitative test. Eravacycline 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 pneumoniae

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Image /page/7/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle divided into two halves. The top half is a solid dark blue color, and the bottom half is a gradient that transitions from yellow to green. The word "BIOMÉRIEUX" is written in white, sans-serif font in the center of the blue half of the circle.

In vitro data are available, but clinical significance is unknown: Citrobacter koseri Klebsiella (Enterobacter) aerogenes

G. Performance Overview and Conclusion:

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

VITEK® 2 AST-GN Eravacycline demonstrated acceptable performance of 97.0% overall Essential Agreement and 99.1% overall Category Agreement with the reference method. Reproducibility and Quality Control demonstrated acceptable results.

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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.”