Thermo Scientific™ Oxoid™Antimicrobial Susceptibility Test (AST) Discs are used in the semi quantitative agar diffusion test method for in vitro susceptibility testing.

The Thermo Scientific Oxoid Meropenem/Vaborbactam Disc (30 can be used to determine susceptibility to Meropenem/Vaborbactam against the following bacteria for which Meropenem/Vaborbactam has been shown to be active both clinically and in vitro:

Escherichia coli
Klebsiella pneumoniae
Enterobacter cloacae species complex

Device Description

Thermo Scientific Oxoid Meropenem/Vaborbactam Disc (30μg) MEV30 Antimicrobial Susceptibility Test Discs are 6mm. discs prepared by impregnating high quality absorbent paper with accurately determined amounts of Meropenem and Vaborbactam. The Disc is clearly marked on both sides with the code MEV30. The code designates the agent (Meropenem/Vaborbactam) and the drug content (30µg).

Oxoid discs are supplied in cartridges containing 50 discs each, there are 5 cartridges per pack. Each cartridge is individually sealed together with a desiccant capsule in a foil covered seethrough blister pack. Oxoid discs can be dispensed using an Oxoid Disc Dispenser.

Meropenem/Vaborbactam Disc (30μg) MEV30 Disc Content: Meropenem 20μg / Vaborbactam10μg.

AI/ML Overview

The medical device under consideration is the Thermo Scientific Oxoid Meropenem/Vaborbactam Disc (30ug) MEV30, an Antimicrobial Susceptibility Test Disc.

Here's an analysis based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The primary acceptance criterion appears to be Category Agreement (CA) with a predicate device.

Acceptance Criterion (Implicit)	Reported Device Performance
High Category Agreement (CA) with predicate device	Enterobacteriaceae (Total=375): CA = 99.2% (372/375)
	K. pneumoniae (184 isolates)
	Escherichia coli (121 isolates)
	Enterobacter cloacae spp. complex (35 isolates)
Performance in accordance with antibiotic manufacturer recommendations	Product performance is in accordance with the recommendations of the manufacturer of the antibiotic.
Quality Control (QC) within acceptable ranges	Acceptable QC ranges established and tested (see Table 5.3)

2. Sample Sizes Used for the Test Set and Data Provenance:

Test Set Sample Size:
- 300 clinical isolates
- 75 challenge isolates
- Total: 375 isolates (Enterobacteriaceae specific, including K. pneumoniae, Escherichia coli, and Enterobacter cloacae spp. complex)
Data Provenance: Not explicitly stated regarding country of origin or if prospective/retrospective. However, clinical isolates suggest real-world samples.

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

This information is not provided in the document. The study compares the device against a "predicate device" and potentially "CLSI approved standards M02 and M100" for interpretation, rather than relying on human expert consensus for a de novo ground truth.

4. Adjudication Method for the Test Set:

This information is not provided. The study design focuses on direct comparison to a predicate device and adherence to established interpretive criteria.

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:

This is not applicable. The device is an antimicrobial susceptibility test disc, not an AI-powered diagnostic tool requiring human reader interpretation in the context of an MRMC study. Its performance is determined by the zone diameter measurement.

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

This is not applicable in the context of a typical standalone algorithm study for AI. The "device" itself (the disc) provides a direct output (zone diameter) which is then interpreted against established criteria. It doesn't involve an algorithm in the AI sense. However, the study did evaluate the device's performance independently, comparing its output to a predicate device and established criteria.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.):

The ground truth for the performance study is implicitly based on the results obtained from the predicate device (HardyDisk Meropenem/Vaborbactam 20/10 µg (MEV30), K172621) and the established susceptibility interpretive criteria (CLSI approved standards M02 and M100, presented in Table 5.2). The predicate device's performance would have previously been established as accurate.

8. The Sample Size for the Training Set:

This is not applicable/not provided. The device is a physical diagnostic disc, not a machine learning model that requires a training set in the conventional sense.

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

This is not applicable. As explained above, there is no "training set" for this type of device.

Summary of the Study:

The study was a comparative evaluation of the Thermo Scientific Oxoid Meropenem/Vaborbactam Disc against a legally marketed predicate device (Hardy Meropenem Vaborbactam disk) for determining antimicrobial susceptibility.

Objective: To demonstrate that the performance of the new disc is equivalent to the predicate device.
Methodology:
- Comparison of zone diameter measurements for 375 isolates (300 clinical, 75 challenge) of Enterobacteriaceae (including K. pneumoniae, E. coli, and E. cloacae spp. complex).
- Assessment of Category Agreement (CA) between the new device and the predicate.
- Quality Control (QC) and reproducibility studies were also performed.
Results: A Category Agreement of 99.2% was achieved for Enterobacteriaceae (372 out of 375 isolates) when compared to the predicate device. The zone diameter interpretive criteria and acceptable quality control ranges were established based on CLSI standards.
Conclusion: The study concluded that the disc performance was equivalent to the predicate device and in accordance with the recommendations of the antibiotic manufacturer.

Limitations Noted in the Document:

The ability of the disc to detect resistance in species other than K. pneumoniae is unknown due to an insufficient number of resistant strains at the time of testing.
Performance for Enterobacteriaceae with specific resistance mechanisms (overexpression of efflux pumps and/or lower expression of porins) is unknown.

Summary

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September 27, 2018

Oxoid Limited (Part of Thermo Fisher Scientific) Philip Brame Regulatory Affairs Manager Wade Road Basingstoke, RG24 8PW Gb

Re: K181975

Trade/Device Name: Thermo Scientific Oxoid Meropenem/Vaborbactam Disc (30ug) MEV30 Regulation Number: 21 CFR 866.1620 Regulation Name: Antimicrobial susceptibility test disc Regulatory Class: Class II Product Code: JTN Dated: July 23, 2018 Received: July 24, 2018

Dear Philip Brame:

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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

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/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Steven R. Gitterman -S for

Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K181975

Device Name

Thermo Scientific Oxoid Meropenem/Vaborbactam Disc (30ug) MEV30

Indications for Use (Describe)

Thermo Scientific™ Oxoid™Antimicrobial Susceptibility Test (AST) Discs are used in the semi quantitative agar diffusion test method for in vitro susceptibility testing.

Escherichia coli Klebsiella pneumoniae Enterobacter cloacae species complex

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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510(K) SUMMARY

In accordance with 21 CFR 807.87(h) and (21 CFR 807.92) the 510(k) Summary for the Thermo Scientific Oxoid Meropenem/Vaborbactam Disc (30μg) MEV30 is provided below.

Device Common Name:	Thermo Scientific Oxoid Meropenem/Vaborbactam Disc (30µg)MEV30
Device Trade Name:	Thermo Scientific Oxoid Meropenem/Vaborbactam Disc (30µg)MEV30
Applicant:	Oxoid Ltd
Contact:	Philip BrameRegulatory Affairs Manager Oxoid Ltd.Wade Road BasingstokeHampshire RG24 8PWUnited Kingdom+44 (0)1256 694279phil.brame@thermofisher.com
Date Prepared:	23-JULY-2018
Regulation:	21 CFR 866.1620
Panel:	Microbiology
Product Code:	JTN

Indications for Use:

Thermo Scientific Oxoid Antimicrobial Susceptibility Test (AST) Discs are used in the semi quantitative agar diffusion test method for in vitro susceptibility testing.

The Thermo Scientific Oxoid Meropenem /Vaborbactam Disc (30u) MEV 30 can be used to determine susceptibility to Meropenem/Vaborbactam against the following bacteria for which Meropenem/Vaborbactam has been shown to be active both clinically and in vitro:

Escherichia coli ●
Klebsiella pneumoniae ●
Enterobacter cloacae species complex. ●

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Device Description:

(30µg).

Meropenem/Vaborbactam Disc (30μg) MEV30 Disc Content: Meropenem 20μg / Vaborbactam10μg.

Device Comparison:

Table 5.1: Similarities and differences between proposed and predicate devices.

Similarities	Thermo Scientific OxoidMeropenem/VaborbactamDisc (30µg) MEV30	Predicate DeviceHardyDiskMeropenem/Vaborbactam20/10 µg (MEV30)K172621
Intended Use	Oxoid AntimicrobialSusceptibility Test Discsare used in the semiquantitative agar diffusiontest method for in vitrosusceptibility testing.	Same
Antimicrobial Agent(s)	Meropenem/Vaborbactam	Same
Antimicrobial AgentConcentration	Meropenem20µg/Vaborbactam 10µg	Same
Test Method	Semi quantitative agardiffusion test methodusing antimicrobial discsimpregnated with anantimicrobial agent.	Same
Result Interpretation Method	Measurement of zone size	Same

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	Thermo Scientific OxoidMeropenem/VaborbactamDisc (30µg) MEV30	Predicate DeviceHardyDiskMeropenem/Vaborbactam20/10 µg (MEV30)K172621
Interpretation	Require the user todetermine categoricalinterpretations (S/I/R) usingthe measured zone diameteragainst CLSI approvedstandards M02 and M100.	Same
Differences
Product Name	OxoidMeropenem/VaborbactamDisc (30µg) MEV30	HardyDiskMeropenem/Vaborbactam20/10 µg (MEV30)

Substantial Equivalence Conclusion:

Devices are substantially equivalent.

Performance Data:

The performance of the disc has been assessed through a comparative study with a predicate device (Hardy Meropenem Vaborbactam disk) on clinical and challenge isolates. The study also included QC and reproducibility studies. A summary of the results is detailed in section 20. The conclusion from the studies was that the disc performance was equivalent to the predicate device. A summary of the performance characteristics is presented here:

Performance Characteristics

The Oxoid Meropenem/Vaborbactam disc (30 µg, MEV30) was compared with a cleared disk (predicate) of the same antimicrobial, mass and concentration. The study included 300 clinical and 75 challenge isolates. The category agreement (CA) with the predicate was as follows:

Organism(s)	Total	CA (#)	CA (%)
Enterobacteriaceae 1, 2, 3	375	372	99.2

1 Including indicated organisms K. pneumoniae (184), Escherichia coli (121), and Enterobacter cloacae spp. Complex (35).

2The safety and efficacy of meropenem/vaborbactam in treating clinical infections due to Gram-Negative organisms other than Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex may or may not have been established in adequate and well-controlled clinical significance of such susceptibility

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information in those instances is unknown.

3The performance of Oxoid Meropenem/Vaborbactam disk (30 ug) MEV30 is unknown for Enterobacteriaceae with the following resistance mechanisms: overexpression of efflux pumps and/or lower expression of porins.

Product performance is in accordance with the recommendations of the manufacturer of the antibiotic.

Limitations

The ability of the Oxoid Meropenem/vaborbactam disc to detect resistance in species other than K. pneumoniae is unknown because an insufficient number of resistant strains were available at the time of comparative testing. If such a strain is observed, it should be submitted to a reference laboratory for further testing.

Table 5.2: Susceptibility Interpretive Criteria for Meropenem/Vaborbactam Disc (30μg)

Pathogen	Disc Diffusion ZoneDiameter (mm)
	S	I	R
Enterobacteriaceae	$\u226517$	14-16	$\u226413$

Abbreviations: S=Susceptible; I=intermediate; R=Resistant

Quality Control testing was completed in accordance with CLSI Performance Standards For Antimicrobial Disc Susceptibility Tests; Approved Standard - Twelfth Edition M02-A12 and Performance Standards for Antimicrobial Susceptibility Testing M100 - S27.

Quality Control testing was completed each day susceptibility testing is performed or weekly if satisfactory performance can be documented according to the CLSI Standard.

Control Zone Diameter Limits (mm) for organisms recommended to be tested are:

Table 5.3: Acceptable Quality Control Ranges for Meropenem/Vaborbactam Disc (30μg) Susceptibility Testing

Quality Control Organism	Disc Diffusion ZoneDiameter (mm)
Klebsiella pneumoniae ATCC BAA-1705*	21-27
Klebsiella pneumoniae ATCC BAA-2814*	16-20
Escherichia coli ATCC 25922	31-37
Klebsiella pneumoniae ATCC 700603	29-35

ATCC = American Type Culture Collection

*KPC-producing K. pneumoniae included for the QC of vaborbactam activity

Regulation Number and Section

§ 866.1620 Antimicrobial susceptibility test disc.

(a)
Identification. An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).