ETEST® is a manual, quantitative technique for the determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.

Fosfomycin has been shown to be active against the Gram-positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.

ETEST® (FO) can be used to determine the MIC of Fosfomycin against the following microorganisms:

Active both in vitro and in clinical infections:

Escherichia coli
Enterococcus faecalis

Device Description

ETEST® is a thin, inert and non-porous plastic strip carrying the MIC reading scale in µg/mL on one side and a predefined antibiotic gradient on the other side.

When the strip is applied to an inoculated agar surface, the preformed antibiotic gradient immediately transfers into the agar matrix, then forming a stable, continuous and exponential gradient of antibiotic concentrations directly underneath the strip. Bacterial growth becomes visible during incubation, and a symmetrical inhibition ellipse centered along the strip appears. The MIC value is read from the scale in terms of ug/mL at complete inhibition of bacterial growth, where the pointed end of the ellipse intersects the strip.

ETEST® Fosfomycin contains a range of fosfomycin from 0.032 to 512 ug/mL.

AI/ML Overview

The provided document is a 510(k) premarket notification for a medical device called ETEST® Fosfomycin (FO) (0.032-512 ug/mL). This device is an Antimicrobial Susceptibility Test Powder used to determine the Minimum Inhibitory Concentration (MIC) of fosfomycin against certain bacteria.

Here's an analysis of the acceptance criteria and the study proving the device meets those criteria, based only on the provided text. Please note that the document is a regulatory submission, not a detailed scientific paper, so some requested information may not be explicitly stated or might not be applicable to this type of device (e.g., "human readers" for an in-vitro diagnostic).

1. A table of acceptance criteria and the reported device performance

The acceptance criteria for this type of device are generally qualitative (e.g., "acceptable performance," "substantially equivalent," "meets guidance document performance requirements") and quantitative, primarily focusing on "Essential Agreement" and "Category Agreement" with a reference method. The document states that ETEST® Fosfomycin (FO) "demonstrated substantially equivalent performance when compared with the CLSI M07-A11 January 2018 agar microdilution reference method, following rules as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009 and following specifications as defined in CLSI M100 30th Ed. (January 2020)."

While specific numerical acceptance thresholds are not explicitly listed in the document for Essential Agreement (EA) and Category Agreement (CA), the reported performance is presented as meeting acceptable levels. The predicate device also states "Meets Guidance Document Performance Requirements: Yes." This implies the acceptance criteria for EA and CA were those outlined in the referenced FDA Guidance Document and CLSI standards.

Metric (Implied Acceptance Criteria based on successful submission)	Reported Performance (Enterococcus faecalis)	Reported Performance (Escherichia coli)
% Essential Agreement (EA)1	97.9%	90.8%
% Category Agreement (CA)2	93.7%	99.2%
Reproducibility	> 95% (Overall)	> 95% (Overall)
Quality Control	> 95% of the time (Results within expected range)	> 95% of the time (Results within expected range)

1 EA = % of MIC values within ± 1 dilution of the reference method.
2 CA = Correct determination of susceptibility category (e.g., Susceptible, Intermediate, Resistant)

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

Test Set Sample Size:
- Enterococcus faecalis: 191 strains
- Escherichia coli: 238 strains
Data Provenance: The document states "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates the data is retrospective (using existing clinical isolates and stock cultures) and likely prospective (fresh clinical isolates). The country of origin is not explicitly stated, but bioMérieux is a French company.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not applicable to this type of device and study. The ground truth for antibiotic susceptibility testing (AST) devices is established by a standardized, laboratory-based reference method (CLSI agar microdilution method), not by human expert opinion or consensus.

4. Adjudication method for the test set

Not applicable. The ground truth is determined by a standardized laboratory method, not by human interpretation requiring adjudication.

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

Not applicable. This device is an in-vitro diagnostic for antimicrobial susceptibility testing. It does not involve human readers interpreting images, nor does it incorporate AI assistance in the way typically seen in radiology or ophthalmology devices. The comparison is between the test device (ETEST) and a laboratory reference method (CLSI agar microdilution).

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

This concept is also not directly applicable in the same way it would be for an AI algorithm interpreting images. The ETEST operates as a "standalone" laboratory test in that its result (the MIC value) is read directly from the strip after incubation. There isn't an "algorithm" in the typical AI sense; rather, it's a defined chemical gradient interaction with bacterial growth. The performance study evaluates the device's accuracy in determining MIC and category agreement compared to a reference method, which is essentially its "standalone" performance.

7. The type of ground truth used

The ground truth used was the CLSI (Clinical and Laboratory Standards Institute) M07-A11 January 2018 agar microdilution reference method. This is a laboratory-based reference method widely accepted as the gold standard for antimicrobial susceptibility testing. It's not expert consensus, pathology, or outcomes data in this context.

8. The sample size for the training set

The document does not explicitly state the sample size used for a "training set." This type of regulatory submission outlines the performance of the device against a reference method, which corresponds to what would typically be a "test set" in an AI/ML context. For a device like ETEST, which is a physical consumable strip with a pre-defined chemical gradient, there isn't a traditional "training" phase for an algorithm in the way a machine learning model would be trained. The development and optimization of the gradient would occur during product development, but this information is not part of the 510(k) submission.

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

As described in point 8, there isn't a "training set" in the machine learning sense for this device. The physical characteristics and performance of the ETEST strip are developed and characterized, and then validated against the CLSI reference method. The "ground truth" for evaluating the performance of the final device (the "test set") is consistently the CLSI agar microdilution reference method.

Summary

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November 12, 2021

bioMerieux SA Marine Taravant Regulatory Affairs Specialist 376, chemin de l'Orme Marcy-l'Etoile, 69280 France

Re: K210757

Trade/Device Name: ETEST Fosfomycin (FO) (0.032-512 ug/mL) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: JWY Dated: March 12, 2021 Received: March 15, 2021

Dear Marine Taravant:

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. (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

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Indications for Use

510(k) Number (if known)

K210757

Device Name ETEST® Fosfomycin (FO) (0.032-512 ug/mL)

Indications for Use (Describe)

Fosfomycin has been shown to be active against the Gram-positive aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.

ETEST® (FO) can be used to determine the MIC of Fosfomycin against the following microorganisms:

Active both in vitro and in clinical infections:

Escherichia coli
Enterococcus faecalis

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 is a circular logo for BIOMÉRIEUX. The top half of the circle is a dark blue color, and the bottom half is a gradient of yellow and green. The word "BIOMÉRIEUX" is written in white, sans-serif font in the center of the blue portion of the circle.

ETEST® FOSFOMYCIN (FO) (0.032-512 µg/mL)

A. 510(k) Submission Information:

Submitter's Name:	bioMerieux SA
Address:	376 Chemin de l'Orme
	69280 Marcy-l'Etoile, FRANCE
	Contact Person:
	Marine Taravant

Phone Number:	+33 (0)4 78 87 21 26
Date of Preparation:	March 12th, 2021

B. Device Name:

Formal/Trade Name:	ETEST® FOSFOMYCIN (FO) (0.032–512 µg/mL)
Classification Name:	21 CFR 866.1640
	Manual Antimicrobial Susceptibility Test SystemsProduct Code: JWY
Common Name(s):	ETEST® FOSFOMYCIN; ETEST® FO
C. Predicate Device:(K192050)	ETEST® ERAVACYCLINE (ERV) (0.002-32 µg/mL)

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D. Device Description:

ETEST® is a thin, inert and non-porous plastic strip carrying the MIC reading scale in µg/mL on one side and a predefined antibiotic gradient on the other side.

ETEST® Fosfomycin contains a range of fosfomycin from 0.032 to 512 ug/mL.

E. Intended Use:

ETEST® is a manual, quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in ug/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.

Fosfomycin has been shown to be active against the Gram-positive and Gram-negative aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.

ETEST® FO can be used to determine the MIC of Fosfomycin against the following microorganisms:

Active both in vitro and in clinical infections:

-Escherichia coli
-Enterococcus faecalis

F. Summary of the technological characterictics of the new device in comparison to those of the predicate device.

The similarities and differences of ETEST® Fosfomycin (FO) when compared to the predicate device, ETEST® Eravacycline (ERV) (K192050) are described in the table below:

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	Similarities
	Test Device	Predicate Device
	ETEST® Fosfomycin (FO)(0.032-512 µg/mL)	ETEST® Eravacycline (ERV)(0.002-32 µg/mL) (K192050)
Intended Use	ETEST® is a manual, quantitative technique for the determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in µg/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.	ETEST® is a manual, quantitative technique for determination of antimicrobial susceptibility of non-fastidious Gram-negative and Gram-positive aerobic bacteria and fastidious bacteria. The system comprises a predefined antibiotic gradient which is used to determine the Minimum Inhibitory Concentration (MIC, in µg/mL) of different antimicrobial agents against microorganisms tested on agar media after overnight incubation.
	Fosfomycin has been shown to be active against the aerobic microorganisms listed below according to the FDA label for this antimicrobial agent.	Eravacycline has been shown to be active against most isolates of the bacteria listed below according to the FDA label for this antimicrobial agent;
	ETEST® FO can be used to determine the MIC of fosfomycin against the	ETEST® ERV can be used to determine the MIC of Eravacycline against the
Test Device	Predicate Device
following microorganisms:Active both in vitro and inclinical infections:Ο Escherichia coliΟ Enterococcus faecalisClinical &ChallengePerformance Data	following microorganisms.Active both in vitro and inclinical infections:Aerobes: Gram-negative:Citrobacter freundii,Enterobacter cloacae,Escherichia coli,Klebsiella oxytoca,Klebsiella pneumoniae. Gram-positive:Enterococcus faecalis,Enterococcus faecium. In vitro data are available forthe following microorganisms,but clinical significance isunknown:Citrobacter koseri Klebsiella aerogenes
Enterococcus faecalis:EA =97.9%CA = 93.7%Escherichia. coli:EA= 90.8%CA= 99.2%	Enterobacteriaceae:EA = 99.4%CA = 98.0%Enterococcus faecalis andEnterococcus faeciumEA= 100%CA= 94.9%
Reproducibility	Overall reproducibility results > 95%	Overall reproducibility results > 95%
Quality Control	Results within expected range > 95% of the time.	Results within expected range > 95% of the time.
Meets GuidanceDocumentPerformanceRequirements	Yes	Yes
Differencies
	ETEST® Fosfomycin (FO)(0.032-512 µg/mL)	ETEST® Eravacycline (ERV)(0.002-32 µg/mL) (K192050)
AntimicrobialAgent	Fosfomycin	Eravacycline
Product scale	0.032-512 µg/mL	0.002-32 µg/mL

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G. Performance Overview

ETEST® Fosfomycin (FO) (0.032-512 µg/mL) demonstrated substantially equivalent performance when compared with the CLSI M07-A11 January 2018 agar microdilution reference method, following rules as defined in the FDA Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA, issued on August 28, 2009 and following specifications as defined in CLSI M100 30th Ed. (January 2020).

This Premarket Notification (510[k]) presents data in support of ETEST® Fosfomycin (FO) (0.032-512 ug/mL) for Escherichia coli and Enterococcus faecalis.

External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains. The external evaluations were designed to establish the performance of ETEST® Fosfomycin (FO) (0.032-512 ug/mL) by comparing with the CLSI agar microdilution reference method.

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ETEST® Fosfomycin (FO) (0.032-512 µg/mL) demonstrated acceptable performance as presented in Table 1 below:

	Strains(N)	% EssentialAgreement(EA)a)	% CategoryAgreement(CA)
Enterococcus faecalis b)	191	97.9	93.7
Escherichia coli b)c)	238	90.8	99.2

Table 1: Performance Characteristics for ETEST® Fosfomycin

Notes:

a) EA = % of MIC values within ± 1 dilution of the reference method.

b) The optional Inoculator RETRO C80™ and Applicator SIMPLEX C76™ can be used to inoculate plates and apply ETEST® strips to agar media. In the ETEST® Fosfomycin clinical studies, swabs were used for plate inoculation/ streaking, and the Vacuum Pen NEMA C88TM were used for ETEST® strip application
ETEST® Fosfomycin MIC values tended to be in exact agreement or at least one doubling dilution c) lower when testing Escherichia coli compared to the reference agar dilution method.

Reproducibility and Quality Control demonstrated acceptable results.

Conclusion:

The performance data presented in this submission support a substantial equivalence decision. ETEST® Fosfomycin (FO) (0.032-512 ug/mL) is substantially equivalent to ETEST® Eravacycline (ERV) (0.002-32 µg/mL) (K192050).

Regulation Number and Section

§ 866.1640 Antimicrobial susceptibility test powder.

(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).