VITEK® 2 AST-Gram Positive Lefamulin is designed for antimicrobial susceptibility testing of Gram positive microorganisms 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 Positive Lefamulin is a quantitative test. Lefamulin 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: Staphylococcus aureus (methicillin-susceptible isolates)

The VITEK® 2 Gram-positive Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Staphylococcus spp., and S. agalactive 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 (0).

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-GP Lefamulin (≤ 0.03 –>4 µg/mL) has the following concentrations in the card: 0.125, 0.5, 1, and 2 (equivalent standard method concentration by efficacy in ug/mL).

AI/ML Overview

The VITEK® 2 AST-Gram Positive Lefamulin (≤ 0.03 - ≥4 µg/mL) device is an antimicrobial susceptibility testing system designed for Gram-positive microorganisms. The acceptance criteria and performance of the device are detailed below.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (from FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems)	Reported Device Performance (VITEK® 2 AST-GP Lefamulin)
Essential Agreement (EA)	Not explicitly stated in the provided text, but generally expected to be ≥90% for quantitative ASTs.	90.8% (367/404)
Category Agreement (CA)	Not explicitly stated in the provided text, but generally expected to be ≥90% for categorical ASTs.	99.8% (403/404)
Very Major Error (VME)	Not explicitly stated in the provided text, but generally expected to be ≤1.5%	0.0% (0/3)
Major Error (ME)	Not explicitly stated in the provided text, but generally expected to be ≤3%	0.2% (1/401)
Minor Error (mE)	Not explicitly stated in the provided text, but typically also considered in agreement measurements.	N/A (Not reported separately within the table for Lefamulin)
Reproducibility	Acceptable results	100.0%

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

The test set included:

404 isolates for Essential Agreement reporting and 404 isolates for Category Agreement reporting (derived from the numerators/denominators in Table 2).
3 resistant isolates were tested for VME (Very Major Error)
401 susceptible isolates were tested for ME (Major Error)

The data provenance is described as 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 of the data or explicitly state whether the study was retrospective or prospective.

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 given text.

4. Adjudication method for the test set

This information is not provided in the given text.

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

A multi-reader multi-case (MRMC) comparative effectiveness study with human readers assisted by AI is not applicable to this device. This device is an automated antimicrobial susceptibility test system, not an AI-assisted diagnostic tool interpreted by human readers.

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

Yes, a standalone performance evaluation was done. The VITEK® 2 AST-GP Lefamulin system's performance was compared directly to the CLSI broth microdilution reference method (the ground truth), without human intervention in the interpretation of the VITEK® 2 results. The system automatically generates MIC values and interpretive categories.

7. The type of ground truth used

The ground truth used was the CLSI broth microdilution reference method, incubated at 16-20 hours.

8. The sample size for the training set

The document does not explicitly mention a separate "training set" or its sample size. The description focuses on the external evaluation data used for performance assessment. As an AST system, the device's "training" for MIC determination is inherent in its design based on established microdilution principles and may not involve a distinct, large-scale machine learning training set in the way an AI algorithm might.

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

Since a distinct training set is not explicitly mentioned as per the prompt's context (e.g., for an AI algorithm), details on how its ground truth was established are not provided. The device's operation is based on established microbiological principles, and its performance is validated against the CLSI broth microdilution reference method.

Summary

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March 11, 2024

bioMerieux, Inc. Anne Rasponi Senior Regulatory Affairs Specialist 595 Anglum Road Hazelwood, Missouri 63042

Re: K234000

Trade/Device Name: VITEK 2 AST-Gram Positive Lefamulin (<=0.03 - >=4 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, LTT, LTW Dated: December 15, 2023 Received: December 18, 2023

Dear Anne Rasponi:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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,

Natasha Grif

Natasha Griffin O.B.O. 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

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Indications for Use

510(k) Number (if known)

K234000

Device Name

VITEK 2 AST-Gram Positive Lefamulin (≤0.03 - ≥4 µg/ml)

Indications for Use (Describe)

Active both in vitro and in clinical infections: Staphylococcus aureus (methicillin-susceptible isolates)

Type of Use (Select one or both, as applicable)X 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-GP Lefamulin (≤ 0.03 ->4 µg/mL)

A. 510(k) Submission Information:

	Submitter's Name:	bioMérieux, Inc.
	Address:	595 Anglum RoadHazelwood, MO 63042
	Contact Person:	Anne RasponiRegulatory Affairs Specialist
	Phone Number:	314-506-8223
	Fax Number:	314-731-8689
	Date of Preparation:	December 15, 2023
B. Device Name:
	Formal/Trade Name:	VITEK® 2 AST-Gram-Positive Lefamulin (≤ 0.03 - ≥4µg/mL)
	Classification Name:	21 CFR 866.1645Fully Automated Short-Term Incubation CycleAntimicrobial Susceptibility SystemProduct Code LON, LTT, LTW
	Common Name:	VITEK® 2 AST-GP Lefamulin
C. Predicate Device:
		VITEK® 2 AST-GP Daptomycin (≤0.12 - ≥8 µg/mL)(K230864)

D. Device Description:

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VITEK® 2 AST-GP Lefamulin (≤ 0.03 –>4 µg/mL) has the following concentrations in the card: 0.125, 0.5, 1, and 2 (equivalent standard method concentration by efficacy in ug/mL).

E. Substantial Equivalence Information

The similarities and differences of the VITEK 2 AST-GP Lefamulin (≤ 0.03 – ≥4 µg/mL) when compared to the predicate device, VITEK 2 AST-GP Daptomycin (≤0.12 - ≥8 µg/mL) (K230864), are described in the following table.

Item	Device:VITEK® 2 AST-GP Lefamulin	Predicate Device:VITEK® 2 AST-GP Daptomycin (K230864)
Intended Use	General Device Characteristic SimilaritiesVITEK® 2 AST-GP Lefamulin( $≤0.03 -≥4 µg/mL$ ) is designedfor antimicrobial susceptibilitytesting of Gram-positivemicroorganisms and is intendedfor use with the VITEK® 2 andVITEK® 2 Compact Systems asa laboratory aid in thedetermination of in vitrosusceptibility to antimicrobialagents. VITEK® 2 AST-GPLefamulin is a quantitative test.Lefamulin has been shown to beactive against most strains of themicroorganisms listed below,according to the FDA label forthis antimicrobial.The VITEK® 2 Gram-PositiveSusceptibility Card is intendedfor use with the VITEK® 2Systems in clinical laboratoriesas an in vitro test to determinethe susceptibility ofEnterococcus spp.,Staphylococcus spp., and	General Device Characteristic SimilaritiesVITEK® 2 AST-GP Daptomycin( $≤0.12 - ≥8 µg/mL$ ) is designedfor antimicrobial susceptibilitytesting of Gram-positivemicroorganisms and is intendedfor use with the VITEK® 2 andVITEK® 2 Compact Systems as alaboratory aid in thedetermination of in vitrosusceptibility to antimicrobialagents. VITEK® 2 AST-GPDaptomycin is a quantitative test.Daptomycin has been shown tobe active against most strains ofthe microorganisms listed below,according to the FDA label forthis antimicrobial.The VITEK® 2 Gram-PositiveSusceptibility Card is intended foruse with the VITEK® 2 Systemsin clinical laboratories as an in vitro test to determine thesusceptibility of Enterococcusspp., Staphylococcus spp., andStreptococcus agalactiae to
Item	Device:VITEK® 2 AST-GP Lefamulin	Predicate Device:VITEK® 2 AST-GPDaptomycin (K230864)
General Device Characteristic Similarities
	Streptococcus agalactiae toantimicrobial agents when usedas instructed.	antimicrobial agents when used asinstructed.
Test Methodology	Automated quantitativeantimicrobial susceptibility testfor use with the VITEK® 2 andVITEK® 2 Compact Systems todetermine the in vitrosusceptibility of microorganisms	Same
Inoculum	Saline suspension of organism	Same
Test Card	Gram-positive (AST-GP)Susceptibility Card	Same
Instrument	VITEK® 2 and VITEK® 2Compact Systems	Same
Type of test	Quantitative test	Same
Differences
Antimicrobial Agent	Lefamulin	Daptomycin
Concentrations	0.125, 0.5, 1, 2	0.5, 1, 2, 4, 16
Breakpoints	Staphylococcus aureus (MSSA)(S/I/R) ≤ 0.25 / - / -	Staphylococcus aureus(S/I/R) ≤ 1 / - / -Enterococcus faecalis(S/I/R) ≤ 2 / 4 / ≥ 8
IndicatedOrganisms	Active in vitro and in clinicalinfections:Staphylococcus aureus(methicillin-susceptible isolates)	Active both in vitro and in clinicalinfections:Enterococcus faecalis(vancomycin- susceptible isolatesonly)Staphylococcus aureus (includingmethicillin-resistant isolates)In vitro data are available. buttheir clinical significance isunknown:Enterococcus faecalis(vancomycin- resistant isolates)

Table 1: Substantial Equivalence

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F. Intended Use:

VITEK® 2 AST-GP Lefamulin is designed for antimicrobial susceptibility testing of Gram-positive microorganisms and is intended for use with the VITEK® 2 and VITEK® 2 COMPACT Systems in clinical laboratories as a laboratory aid in the determination of in vitro susceptibility to antimicrobial agents when used as instructed. VITEK® 2 AST-GP Lefamulin is a quantitative test. Lefamulin has been shown to be active against the microorganisms listed below. according to the FDA label for this antimicrobial.

Active in vitro and in clinical infections: Staphylococcus aureus (methicillin-susceptible isolates)

The VITEK® 2 AST-GP Lefamulin Susceptibility Card is intended for use with the VITEK® 2 Systems in clinical laboratories as an in vitro test to determine the susceptibility of Enterococcus spp., Staphylococcus spp., and Streptococcus agalactiae to antimicrobial agents when used as instructed.

G. Performance Overview and Conclusion:

VITEK® 2 AST-GP Lefamulin demonstrated substantially equivalent performance when compared with the 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 (Traditional 510(k)) presents data in support of VITEK® 2 AST-GP Lefamulin. 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-GP Lefamulin 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 and VITEK® 2 Compact instrument platforms.

The VITEK 2 AST-GP Lefamulin demonstrated acceptable performance as presented in Table 2 below:

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Antimicrobial	Antimicrobial Code	Antibiotic Version	Bp1	Comment	Essential Agreement Category				Category Agreement				% Reproducibility
					% Error				% Error
					%EA	VME	ME	mE	%CA	VME	ME	mE
Lefamulin	LMU	(Imu01n)	CLSI(FDA)	#, EStaphylococcus aureus	(367/404)90.8	N/A	N/A	N/A	(403/404)99.8	(0/3)0.0	(1/401)0.2	N/A	100.0
VITEK® 2 Lefamulin MIC values tended to be in exact agreement or at least one doubling dilution lower when testing methicillin-susceptible S. aureus compared to the CLSI reference method, broth microdilution. The incubation time (Time of Call) for AST GP cards containing Lefamulin may exceed 16 hours. This extended incubation time is required to generate MIC values.

Table 2: VITEK 2 AST-GP Lefamulin Performance

1 Abbreviations - Bp = breakpoint committee; EA = essential agreement; CA = category agreement; VME = Very Major Error (susceptible result with resistant reference result); ME = Major Error (resistant result with susceptible reference result); mE = minor Error (susceptible or resistant result with an intermediate reference result, or an intermediate result with a susceptible or resistant reference result).

Kev:

= US Food and Drug Administration 510(k) cleared CLSI® = Clinical and Laboratory Standards Institute E = External performance data

Reproducibility and Quality Control demonstrated acceptable results.

The performance data presented in this submission support a substantial equivalence decision. VITEK® 2 AST-GP Lefamulin (≤0.03 ->2 µg/mL) is substantially equivalent to VITEK® 2 AST-GP Daptomycin (K230864).

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.

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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.”