VITEK® 2 AST-Gram Negative Omadacycline 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 Omadacycline in is a quantitative test. Omadacycline 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:
For Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Enterobacter cloacae Klebsiella pneumoniae For Community Acquired Bacterial Pneumonia (CABP): Klebsiella pneumoniae

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 Omadacycline (≤0.25 - >16 µg/mL) has the following concentrations in the card: 0.5, 2. 8 and 16 ug/mL (equivalent standard method concentration by efficacy in us/mL).

AI/ML Overview

This document describes the VITEK® 2 AST-Gram Negative Omadacycline device, an automated antimicrobial susceptibility testing system. The information provided outlines the device's performance against established acceptance criteria, focusing on its ability to accurately determine the susceptibility of Gram-negative bacilli to Omadacycline.

Here's an analysis of the provided information concerning acceptance criteria and supporting studies:

Table of Acceptance Criteria and Reported Device Performance:

The provided document presents the performance of the VITEK® 2 AST-GN Omadacycline against specific criteria. Based on the "FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems," the key performance metrics are Essential Agreement (EA) and Category Agreement (CA), along with Very Major Errors (VME), Major Errors (ME), and Minor Errors (mE).

Metric	Acceptance Criteria (as per FDA Guidance for AST Systems)	Reported Device Performance (Omadacycline) - ABSSSI (E. cloacae, K. pneumoniae)	Reported Device Performance (Omadacycline) - CABP (K. pneumoniae)
Essential Agreement (EA) %	≥ 90% for drug/organism combinations	97.9% (410/419)	98.0% (342/349)
Category Agreement (CA) %	≥ 90% for drug/organism combinations	94.3% (395/419)	93.7% (327/349)
Very Major Errors (VME) %	≤ 1.5% and ≤ 3 VMEs	2.0% (1/51)	2.7% (1/37)
Major Errors (ME) %	≤ 3.0% and ≤ 3 MEs	0.0% (0/343)	0.0% (0/290)
Minor Errors (mE) %	≤ 10.0%	5.5% (23/419)	6.0% (21/349)

Note: The VME percentages of 2.0% and 2.7% are above the typical acceptance criterion of ≤ 1.5%. However, the absolute number of VMEs is 1 in both cases, which might be considered acceptable depending on the specific interpretation of "and ≤ 3 VMEs" in the guidance document for small sample sizes of resistant isolates. The document explicitly states the device "demonstrated acceptable performance."

Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Size:
  - For E. cloacae and K. pneumoniae (ABSSSI): 419 isolates.
  - For K. pneumoniae (CABP): 349 isolates.
- Data Provenance: The study involved an "external evaluation" conducted with "fresh and stock clinical isolates, as well as a set of challenge strains." The document does not specify the country of origin but implies a clinical laboratory setting. It is likely a retrospective collection of isolates from clinical settings.
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

The document describes the "CLSI broth microdilution reference method" as the ground truth. This is a standardized laboratory method, not reliant on individual expert interpretation. Therefore, there were no "experts" in the sense of human readers establishing ground truth for this device; rather, a consensus reference method was used.
Adjudication Method for the Test Set:

Not applicable. The ground truth was established by the CLSI broth microdilution reference method, which is a quantitative laboratory procedure, not a subjective interpretation requiring adjudication.
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:

Not applicable. This device is an automated antimicrobial susceptibility testing system, not an AI-assisted diagnostic imaging or interpretation system requiring human-in-the-loop performance measurement or MRMC studies. Its performance is compared to a reference laboratory method, not human readers.
If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Yes, this was a standalone performance study. The VITEK® 2 AST-GN Omadacycline system's performance (an automated device/algorithm) was evaluated against the CLSI broth microdilution reference method without human interpretation as part of the primary outcome. The system generates an MIC value and interpretive category automatically.
The Type of Ground Truth Used:

The ground truth used was the CLSI broth microdilution reference method, which is a standardized laboratory procedure for determining minimum inhibitory concentrations (MICs) of antimicrobials. This is considered a highly reliable and accepted reference standard in microbiology.
The Sample Size for the Training Set:

The document describes a "Premarket Notification (510[k])" which "presents data in support of VITEK® 2 AST-GN Omadacycline." It mentions "external evaluation" with "fresh and stock clinical isolates, as well as a set of challenge strains." This suggests a validation study, but it does not specify a separate "training set" or its size for the development of the VITEK 2 system's algorithms for omadacycline. The VITEK® 2 system itself is a pre-existing platform, and this submission is for a new antimicrobial agent card. The algorithms for interpreting growth patterns for MIC determination are inherent to the VITEK 2 system's design. The data presented are for validation, not explicit "training."
How the Ground Truth for the Training Set Was Established:

As noted in point 8, a specific "training set" for the Omadacycline card and its ground truth establishment is not explicitly detailed in the provided document. The VITEK® 2 system's underlying interpretive algorithms would have been developed and validated previously using reference methods (like broth microdilution) for various antimicrobials and organisms during the initial development of the VITEK® 2 platform. For new antimicrobial cards, the focus is on validating the new agent's performance against the established reference method as outlined in the provided study.

Summary

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

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a symbol representing the Department of Health & Human Services - USA. To the right of this symbol, there is a blue square with the letters "FDA" in white. Next to the blue square, the words "U.S. FOOD & DRUG ADMINISTRATION" are written in blue.

June 3, 2022

bioMérieux, Inc. Nathan Hardesty Associate Director, Regulatory Affairs 595 Anglum Road Hazelwood, Missouri 63042

Re: K213931

Trade/Device Name: VITEK 2 AST-Gram Negative Omadacycline (<0.25 ->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 Dated: December 15, 2021 Received: December 16, 2021

Dear Nathan Hardesty:

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

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

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 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

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

Indications for Use

510(k) Number (if known)

Device Name

Indications for Use (Describe)

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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."

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

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

510(k) SUMMARY

VITEK® 2 AST-Gram Negative Omadacycline (≤0.25 - >16 µg/mL)

510(k) Submission Information:

Submitter's Name:	bioMérieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Debra BroylesSenior Regulatory Affairs Specialist
Phone Number:	314 -731-8805
Fax Number:	314-731-8689
Date of Preparation:	July 25, 2021
Device Name:
Formal/Trade Name:	VITEK® 2 AST-Gram Negative Omadacycline (≤0.25 -≥16 µg/mL)
Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code: LON, LTW, LTT
Common Name:	VITEK® 2 AST-GN Omadacycline (≤0.25 - ≥16 µg/mL)
Predicate Device:	VITEK® 2 AST-GN Eravacycline (≤0.12 - ≥ 4µg/mL) (K191766)

D. Device Description:

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

Image /page/4/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 center of the blue half of the circle.

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 Omadacycline (≤0.25 - >16 µg/mL) has the following concentrations in the card: 0.5, 2. 8 and 16 ug/mL (equivalent standard method concentration by efficacy in us/mL).

E. Substantial Equivalence Information:

The similarities and differences of the VITEK® 2 AST-GN Omadacycline (≤0.25 - ≥16 µg/mL) when compared to the predicate device, VITEK® 2 AST-GN Eravacycline ( ≤ 0.12 -> 4 ug/mL), are described in the Table 1 below.

Item	Device:VITEK® 2 AST-Gram NegativeOmadacycline( $\leq$ 0.25 - $\geq$ 16 µg/mL)	Predicate:VITEK® 2 AST-GNEravacycline( $\leq$ 0.12 - $\geq$ 4 µg/mL)(K191766)
Similarities
Intended Use	VITEK® 2 AST-Gram NegativeOmadacycline 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 Omadacyclineis a quantitative 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 NegativeEravacycline 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 Eravacycline is aquantitative test.The VITEK® 2 Gram-NegativeSusceptibility Card is intended foruse with the VITEK® 2 Systems inclinical laboratories as an in vitro
Item	Device:VITEK® 2 AST-Gram NegativeOmadacycline(≤0.25 - ≥16 µg/mL)	Predicate:VITEK® 2 AST-GNEravacycline(≤0.12 - ≥4 µg/mL)(K191766)
Similarities
	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
Differences
AntimicrobialAgent	Omadacycline	Eravacycline
Concentrations	0.5, 2, 8, 16	0.25, 1, 2, 4
Indications for use	Omadacycline has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label for thisantimicrobial.	Eravacycline has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label for thisantimicrobial.
	Active in vitro and in clinicalinfections:For ABSSSI:Enterobacter cloacaeKlebsiella pneumoniaeFor CABP:Klebsiella pneumoniae	Active in vitro and in clinicalinfections:Citrobacter freundiiEnterobacter cloacaeEscherichia coliKlebsiella oxytocaKlebsiella pneumoniaeIn vitro data are available, butclinical significance is unknown:
		Citrobacter koseriKlebsiella (Enterobacter)
Item	Device:VITEK® 2 AST-Gram NegativeOmadacycline(≤0.25 - ≥16 µg/mL)	Predicate:VITEK® 2 AST-GNEravacycline(≤0.12 - ≥4 µg/mL)(K191766)
Similarities
aerogenes

Table 1: Substantial Equivalence

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

Image /page/5/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle that is split into two halves. The top half is blue and contains the word "BIOMÉRIEUX" in white letters. The bottom half of the circle is yellow and green.

VITEK® 2 AST-GN Omadacycline

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

Image /page/6/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo is 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.

F. Intended Use:

Active in vitro and in clinical infections:

For Acute Bacterial Skin and Skin Structure Infections (ABSSSI): Enterobacter cloacae Klebsiella pneumoniae For Community Acquired Bacterial Pneumonia (CABP): Klebsiella pneumoniae

G. Performance Overview and Conclusion:

VITEK® 2 AST-GN Omadacycline 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 Omadacycline. 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 Omadacycline by comparing its performance with the CLSI broth microdilution reference

{7}------------------------------------------------

Image /page/7/Picture/0 description: The image shows the logo for bioMérieux, a French multinational biotechnology company. The logo consists of a blue circle at the top, with the company name "BIOMÉRIEUX" in white, sans-serif font. The bottom half of the circle transitions from yellow to green, creating a gradient effect. The overall design is simple and modern, reflecting the company's focus on innovation in the field of diagnostics.

method incubated at 16-24 hrs. The data is representative of performance on both the VITEK® 2 and VITEK® 2 Compact instrument platforms.

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

Antimi-crobial	Antimi-crobialcode	Antimi-crobialVersion	Comment	Essential Agreement Category% Error				Category Agreement% Error
				%EA	VME	ME	mE	%CA	VME	ME	mE
Omada-cycline	OMC	omc01n	ABSSSIE. cloacae *K. pneumoniaeCABPK. pneumoniae	97.9(410/419)98.0(342/349)	N/AN/A	N/AN/A	N/AN/A	94.3(395/419)93.7(327/349)	2.0 (1/51)2.7 (1/37)	0.0(0/343)0.0(0/290)	5.5(23/419)6.0(21/349)

Table 2: VITEK® 2 AST-GN Omadacycline Performance

Reproducibility and Quality Control demonstrated acceptable results.

H. References:

{8}------------------------------------------------

Image /page/8/Picture/0 description: The image shows the logo for bioMérieux. The logo is a circle with a blue top half and a yellow-green bottom half. The word "BIOMÉRIEUX" is written in white letters in the center of the blue half of the circle.

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.
Barry, A.L., The Antimicrobic Susceptibility Test, Principles and Practices, Lea and Febiger, 3. 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.”