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. Plazomicin has been shown to be active against most isolates of the bacteria listed below according to the FDA label for this antimicrobial agent.

ETEST® PLZ can be used to determine the MIC of Plazomicin aqainst the following microorganisms:

Active both in vitro and in clinical infections:

Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Enterobacter cloacae

In vitro data are available for the following microorganisms, but clinical significance is unknown:

Citrobacter freundii
Citrobacter koseri
Klebsiella (Enterobacter) aerogenes
Klebsiella oxytoca
Morganella morganii
Proteus vulgaris
Providencia stuartii
Serratia marcescens

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® Plazomicin contains a range of plazomicin from 0.016 to 256 ug/mL.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the ETEST® Plazomicin (PLZ) device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The device performance is compared to the CLSI M07-A11 broth microdilution reference method. The acceptance criteria are implicitly derived from the CLSI guidance documents and FDA's Class II Special Controls Guidance Document for Antimicrobial Susceptibility Test (AST) Systems.

Performance Metric	Acceptance Criteria (Implicit from Guidance)	Reported Device Performance (ETEST® Plazomicin)
Essential Agreement (EA)a	> 90%	99.0%
Category Agreement (CA)	> 90% (with some exceptions noted for specific organisms where EA is high and errors are minor)	92.8%
Reproducibility	Results within expected range > 95% of the time	Best-case: 100%, Worst-case: 100%
Quality Control	Results within expected range > 95% of the time	Results within expected range > 95% of the time

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

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

Test Set Sample Size: The performance data for Enterobacteriaceae included a total of 605 strains.
- Breakdown by organism: Escherichia coli (78), Klebsiella pneumoniae (89), Proteus mirabilis (63), Enterobacter cloacae (60), Citrobacter freundii (59), Citrobacter koseri (34), Klebsiella (Enterobacter) aerogenes (38), Klebsiella oxytoca (39), Morganella morganii (31), Proteus vulgaris (34), Providencia stuartii (35), and Serratia marcescens (38).
Data Provenance: "External evaluations were conducted with fresh and stock clinical isolates, as well as a set of challenge strains." This indicates a mix of retrospective (stock clinical isolates) and prospective (fresh clinical isolates) data, along with curated challenge strains. The country of origin is not specified but implicitly involves clinical settings relevant to the device's intended use.

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

Not explicitly stated. The ground truth was established by comparing the ETEST® Plazomicin results with the CLSI broth microdilution reference method. This method itself is the gold standard, and its execution and interpretation typically rely on trained laboratory personnel rather than "experts" in the sense of physicians or radiologists adjudicating images.

4. Adjudication Method for the Test Set

Not applicable in the traditional sense for this type of device. The study design involves direct comparison to a reference method (CLSI broth microdilution) rather than expert adjudication of results. Discrepancies (e.g., categorical errors) are noted and explained.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This device is an antimicrobial susceptibility test system, not an imaging device requiring human reader interpretation in the same way. The evaluation focuses on the agreement between the test strip and a reference laboratory method.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done

This is a standalone device performance study. The ETEST® strip visually provides the Minimum Inhibitory Concentration (MIC) value, which is then interpreted. While a human reads the result from the strip, the performance study itself assesses the accuracy of the strip's ability to generate that MIC in comparison to a reference method. It's not an "algorithm" in the typical software sense, but the device's inherent functional performance is evaluated independently.

7. The Type of Ground Truth Used

The ground truth used was the CLSI M07-A11 broth microdilution reference method. This is considered the gold standard for determining antimicrobial susceptibility.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" in the context of device development or algorithm training. The performance study focuses on the evaluation of the finished product using clinical and challenge isolates against a reference method.

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

As no training set is explicitly described for algorithm development, this point is not applicable. The device's underlying mechanism is a physical chemical gradient, not a machine learning algorithm that requires a separate training set. The "development" or "calibration" of the ETEST® strips would involve internal studies to ensure the accuracy of the gradient, likely using similar reference methods.

Summary

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May 7, 2020

bioMérieux S.A. Alexia Bosquet Regulatory Affairs Specialist 376 Chemin de l'Orme Marcy L'Etoile, 69280 France

Re: K200512

Trade/Device Name: ETEST Plazomicin (PLZ) (0.016-256 µg/mL) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: JWY Dated: February 28, 2020 Received: March 2, 2020

Dear Alexia Bosquet:

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, 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) K200512

Device Name ETEST® PLAZOMICIN (PLZ) (0.016-256 µg/mL)

Indications for Use (Describe)

ETEST® PLZ can be used to determine the MIC of Plazomicin aqainst the following microorganisms:

Active both in vitro and in clinical infections:

Escherichia coli
Klebsiella pneumoniae
Proteus mirabilis
Enterobacter cloacae

In vitro data are available for the following microorganisms, but clinical significance is unknown:

Citrobacter freundii
Citrobacter koseri
Klebsiella (Enterobacter) aerogenes
Klebsiella oxytoca
Morganella morganii
Proteus vulgaris
Providencia stuartii
Serratia marcescens

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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Image /page/3/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 across the blue portion of the circle.

ETEST® PLAZOMICIN (PLZ) (0.016-256 µg/mL)

A. 510(k) Submission Information:

Submitter's Name:	bioMerieux SA
Address:	376 Chemin de l'Orme69280 Marcy-l'Etoile, FRANCE
Contact Person:	Alexia BosquetRegulatory Affairs Specialist
Phone Number:	+33 (0)4 78 87 50 20
Date of Preparation:	February 28th, 2020

B. Device Name:

Formal/Trade Name:	ETEST® PLAZOMICIN (PLZ) (0.016–256 µg/mL)
Classification Name:	21 CFR 866.1640
	Manual Antimicrobial Susceptibility Test SystemsProduct Code: JWY
Common Name(s):	ETEST® PLAZOMICIN; ETEST® PLZ
C. Predicate Device:	ETEST® Telavancin (TLA) (0.002-32 µg/mL) (K180936)

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Image /page/4/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 half of the circle is a solid dark blue color, and the text "BIOMÉRIEUX" is written in white, sans-serif font in the center of the blue section. The bottom half of the circle is a gradient that transitions from yellow to green.

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® Plazomicin contains a range of plazomicin from 0.016 to 256 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.

Plazomicin has been shown to be active against most isolates of the bacteria listed below according to the FDA label for this antimicrobial agent.

ETEST® PLZ can be used to determine the MIC of Plazomicin against the following microorganisms:

Active both in vitro and in clinical infections:

-Escherichia coli
-Klebsiella pneumoniae
-Proteus mirabilis
Enterobacter cloacae -

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Image /page/5/Picture/0 description: The image is a logo for the company BIOMÉRIEUX. The logo is a circle with two different colored sections. The top section is a dark blue color and contains the company name in white, sans-serif font. The bottom section is a gradient of yellow and green.

In vitro data are available for the following microorganisms, but clinical significance is unknown:

Citrobacter freundii -
Citrobacter koseri -
-Klebsiella (Enterobacter) aerogenes
Klebsiella oxytoca -
Morganella morganii -
-Proteus vulgaris
Providencia stuartii -
Serratia marcescens -

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

The similarities and differences of ETEST® Plazomicin (PLZ) when compared to the predicate device, ETEST® Telavancin (TLA) (K180936) are described in the table below:

	Test Device	Predicate Device
	Similarities
	ETEST® Plazomicin (PLZ)(0.016-256 µg/mL)	ETEST® Telavancin (TLA)(0.002-32 µg/mL) (K180936)
Intended Use	ETEST® is a manual, quantitativetechnique for determination ofantimicrobial susceptibility ofnon-fastidious Gram-negative andGram-positive aerobic bacteriaand fastidious bacteria.The system comprises apredefined antibiotic gradientwhich is used to determine theMinimum InhibitoryConcentration (MIC, in µg/mL) ofdifferent antimicrobial agentsagainst microorganisms tested onagar media after overnight	ETEST® is a quantitativetechnique for determination ofantimicrobial susceptibility of bothnon-fastidious Gram-negative andGram-positive aerobic bacteriasuch as Enterobacteriaceae,Pseudomonas, Staphylococcus,and Enterococcus species andfastidious bacteria, such asanaerobes, N. gonorrhoeae, S.pneumoniae, Streptococcus andHaemophilus species.The system comprises apredefined antibiotic gradient
Test Device	Predicate Device
incubation.Plazomicin has been shown to beactive against most isolates of thebacteria listed below according tothe FDA label for thisantimicrobial agent.ETEST® PLZ can be used todetermine the MIC of Plazomicinagainst the followingmicroorganisms:Active both in vitro and in clinicalinfections:- Escherichia coli- Klebsiella pneumoniae- Proteus mirabilis- Enterobacter cloacaeIn vitro data are available for thefollowing microorganisms, butclinical significance is unknown:- Citrobacter freundii- Citrobacter koseri- Klebsiella (Enterobacter)aerogenes- Klebsiella oxytoca- Morganella morganii- Proteus vulgaris- Providencia stuartii- Serratia marcescens	which is used to determine theMinimum InhibitoryConcentration (MIC), in µg/mL, ofdifferent antimicrobial agentsagainst microorganisms as testedon agar media using overnightincubation.Telavancin has been shown to beactive against the Gram-positiveaerobic microorganisms listedbelow according to the FDA labelfor this antimicrobial agent.Active both in vitro and in clinicalinfections:• Staphylococcus aureus(including methicillinresistant isolates)• Enterococcus faecalis:(vancomycin-susceptibleonly)
Clinical &ChallengePerformance Data	Enterobacteriaceae:EA = 99.0%CA = 92.8%	Staphylococcus aureus:EA = 98.4%CA = 97.9%
	Test Device	Predicate Device
		Enterococcus faecalis:(vancomycin-susceptible only)EA = 91.6%CA = 97.6%
Reproducibility	Best-case: 100%Worst-case: 100%	Best-case: 100%Worst-case: 100%
Quality Control	Results within expected range> 95% of the time.	Results within expected range> 95% of the time.
Meets GuidanceDocumentPerformanceRequirements	Yes	Yes
Differencies
	ETEST® Plazomicin (PLZ)(0.016-256 µg/mL)	ETEST® Telavancin (TLA)(0.002-32 µg/mL) (K180936)
AntimicrobialAgent	Plazomicin	Telavancin
Claimed species	Enterobacteriaceae	Staphylococcus aureus (includingmethicillin resistant isolates)Enterococcus faecalis(vancomycin-susceptible only)
Product scale	0.016-256 µg/mL	0.002-32 µg/mL

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Image /page/6/Picture/1 description: The image shows a semi-circle shape with a gradient of colors. The left side of the semi-circle is a bright yellow color, which gradually transitions to a green color on the right side. The semi-circle is positioned against a white background, which makes the colors stand out. The overall effect is a smooth and visually appealing gradient.

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G. Performance Overview

ETEST® Plazomicin (PLZ) (0.016-256 ug/mL) demonstrated substantially equivalent performance when compared with the CLSI M07-A11 January 2018 broth 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 29th Ed. (January 2019) and 30th Ed. (January 2020).

This Premarket Notification (510[k]) presents data in support of ETEST® Plazomicin (PLZ) (0.016-256 µg/mL) for Enterobacteriaceae.

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Image /page/8/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 across the center of the blue portion of the circle.

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® Plazomicin (PLZ) (0.016-256 ug/mL) by comparing with the CLSI broth microdilution reference method.

ETEST® Plazomicin (PLZ) (0.016-256 µg/mL) demonstrated acceptable performance as presented in Table 1 below:

	Strains(N)	% EssentialAgreement(EA)a)	% CategoryAgreement(CA)
Enterobacteriaceaeb)c)d)e)f)	રેતે જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દ	99.0	92.8

Table 1: Performance Characteristics for ETEST® Plazomicin

Notes:

EA = % of MIC values within ± 1 dilution of the reference method. a)
b) The performance data presented for Enterobacteriaceae include Escherichia coli (78), Klebsiella pneumoniae (89), Proteus mirabilis (63), Enterobacter cloacae (60), Citrobacter freundii (59), Citrobacter koseri (34), Klebsiella (Enterobacter) aerogenes (38), Klebsiella oxytoca (39), Morganella morganii (31). Proteus vulgaris (34), Providencia stuartii (35) and Serratia marcescens (38).
The optional inoculator and ETEST® strip applicator can be used for plate inoculation and c) applying ETEST® strips onto agar media. In the ETEST® Plazomicin clinical studies, swabs and the Inoculator RETRO C80™ were used for plate inoculation/streaking and forceps and the Vacuum Pen NEMA C88TM were used for ETEST® strip application.
d) The Category Agreement was < 90% for the following organisms: Morganii (67.7%), Proteus mirabilis (85.7%), Providencia stuartii (74.3%), Proteus vulgaris (85.3%) and Serratia marcescens (89.5%). The performance is acceptable since the Essential Agreement was > 90% and all categorical errors were minor and within essential agreement, except for one isolate of Serratia marcescens.
e) ETEST® Plazomicin MIC values tended to be in exact agreement or one doubling dilution lower when testing Morganella morganii compared to the reference broth microdilution method.
ETEST® Plazomicin MIC values tended to be in exact agreement or at least one doubling f) dilution higher when testing Klebsiella (Enterobacter) aerogenes and Klebsiella pneumoniae compared to the CLSI reference broth microdilution method. However, this trending did not impact the Essential or Category Agreement (Klebsiella aerogenes EA:100%, CA:100%; Klebsiella pneumoniae EA:100%; CA:98.9%).

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Limitations:

The ability of ETEST Plazomicin to detect the following resistant isolates is unknown because a sufficient number of resistant isolates were not available at the time of comparative testing: Cirrobacter koseri, Serratia marcescens.

Reproducibility and Quality Control demonstrated acceptable results.

Conclusion:

The performance data presented in this submission support a substantial equivalence decision. ETEST® Plazomicin (PLZ) (0.016-256 µg/mL) is substantially equivalent to ETEST® Telavancin (TLA) (0.002-32 µg/mL) (K180936).

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).