K Number

Device Name

Manufacturer

Liofilchem s.r.l.

Date Cleared

2023-05-18

(85 days)

Product Code

Regulation Number

Type

Panel

Reference & Predicate Devices

N/A

Predicate For

N/A

Intended Use

The ComASP® Cefiderocol 0.008-128 is a quantitative broth microdilution method intended for the in vitro determination of antimicrobial susceptibility of bacteria. ComASP® Cefiderocol consists of polystyrene microtier panels containing lyophilized concentrations of cefiderocol and tubes of media (iron depleted cation adjusted Mueller Hinton broth), which are used to determine the minimum inhibitory concentration (MIC) in ug/mL using over overnight incubation and manual reading procedures. ComASP® Cefiderocol at concentrations of 0.008-128 ug/mL should be interpreted at 16-20 hours of incubation.

ComASP® Cefiderocol can be used to determine the MC of cefiderocol against the following microorganisms for which cefiderocol has been shown to be active clinically and in vitro according to the FDA drug approved label:

Acinetobacter baumannii complex Escherichia coli Enterobacter cloacae complex Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa Serratia marcescens

Device Description

AI/ML Overview

This document is an FDA 510(k) clearance letter for an in vitro diagnostic device, specifically the ComASP Cefiderocol 0.008-128, which is an antimicrobial susceptibility test. The information provided in the prompt is not about an AI/ML medical device, and therefore the concepts of "test set," "training set," "ground truth experts," "adjudication," "MRMC study," "human improvement with AI assistance," or "standalone algorithm performance" are not applicable to this type of device submission.

Antimicrobial susceptibility tests (ASTs) are evaluated based on their ability to accurately determine the Minimum Inhibitory Concentration (MIC) of an antibiotic against a microorganism, and to correctly categorize the susceptibility (e.g., Susceptible, Intermediate, Resistant) compared to a reference method.

Therefore, I cannot fulfill the request as it is phrased for an AI/ML device. However, I can describe the acceptance criteria and the study that would typically be done for an antimicrobial susceptibility test device based on the information that would be relevant to such a device, and extrapolate what "acceptance criteria" and "performance" would mean in this context.

Revised Response based on Antimicrobial Susceptibility Test Device Evaluation:

The ComASP Cefiderocol 0.008-128 is an antimicrobial susceptibility test (AST) device. The acceptance criteria and the study proving it meets these criteria for AST devices typically involve comparing the device's results (MICs and categorical interpretations) to a recognized reference method.

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

For an AST device, acceptance criteria are generally defined as the acceptable rates of agreement between the new device and the reference method for MIC results and categorical interpretations. The reported device performance would be the actual agreement rates achieved in the study.

Acceptance Criteria Category	Acceptance Criteria (e.g., % Agreement)	Reported Device Performance (e.g., % Agreement)
Essential Agreement (EA)	≥ 90% (often 95% or higher)	[Specific percentage reported for each organism-drug combination]
Categorical Agreement (CA)	≥ 90% (often 95% or higher)	[Specific percentage reported for each organism-drug combination]
Major Discrepancies (MD)	≤ 3.0% (false susceptible)	[Specific percentage reported for each organism-drug combination]
Very Major Discrepancies (VMD)	≤ 1.5% (false resistant)	[Specific percentage reported for each organism-drug combination]

Essential Agreement (EA): The MIC result from the device is within one doubling dilution of the reference method's MIC result.
Categorical Agreement (CA): The categorical interpretation (e.g., Susceptible, Intermediate, Resistant) from the device matches the reference method's interpretation.
Major Discrepancies (MD): The device reports "Susceptible" when the reference method reports "Intermediate" or "Resistant." This is a significant error as it could lead to ineffective treatment.
Very Major Discrepancies (VMD): The device reports "Resistant" when the reference method reports "Susceptible." This is a significant error as it could lead to unnecessary use of alternative, potentially more toxic, or broader-spectrum antibiotics.

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

For an AST, the "test set" would be a collection of bacterial isolates.

Sample Size: Typically, hundreds of isolates are tested for each organism-drug combination to ensure robust statistical analysis. A common number is 100-300 isolates per species-drug combination, with a sufficient number of resistant strains (often 50% or more) included to adequately assess VMDs.
Data Provenance:
- Country of Origin: Studies are often conducted at multiple clinical sites across different geographical regions (e.g., US, Europe) to ensure generalizability and capture diverse resistance mechanisms.
- Prospective/Retrospective: Isolates are usually a mix of fresh, prospectively collected clinical isolates and well-characterized challenge strains (retrospectively collected or laboratory strains) with known resistance profiles. This ensures both clinical relevance and the ability to test the device against specific, difficult-to-detect resistance mechanisms.

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

For AST devices, "ground truth" is not established by human experts in the same way as image interpretation. Instead, it is established by a reference method.

Ground Truth Method: The gold standard reference method for MIC determination is typically broth microdilution (BMD) as described by clinical and laboratory standards organizations (e.g., CLSI, EUCAST). This reference BMD is performed meticulously in a laboratory setting.
"Experts": The "experts" involved are highly trained microbiologists and medical technologists who meticulously perform the reference BMD and interpret results according to established guidelines. Their qualifications would include extensive experience in clinical microbiology and proficiency in AST methodologies. The reference method performance itself is standardized and validated, limiting subjectivity.

4. Adjudication method for the test set:

Adjudication as typically understood for AI models (e.g., 2+1, 3+1) is not directly applicable. Discrepancies between the new device and the reference method are thoroughly investigated.

Discrepancy Resolution: If there's a discrepancy, the typical "adjudication" involves:
- Re-testing both the new device and the reference method.
- Confirming isolate identity and purity.
- Potentially testing with an alternative reference method or molecular methods (e.g., sequencing for resistance genes) to understand the discrepancy.
  The goal is not to "vote" on the ground truth, but to understand the reason for the disagreement and ensure the original reference result was accurate.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done:

No, an MRMC study is not conducted for an AST device. The device provides a quantitative (MIC) and categorical result, not an image for human interpretation. Therefore, there's no "human reader" component whose performance would be improved by AI assistance.

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

The AST device is a standalone diagnostic test in terms of its direct output. The "algorithm" is the biochemical reaction and the method for reading the turbidity/growth. The performance evaluation is the standalone performance of the device against the reference method. While humans perform the manual reading for ComASP Cefiderocol (as stated in the Indications for Use: "manual reading procedures"), the evaluation specifically assesses the accuracy of the MIC determination by the device itself once inoculated, incubated, and read.

7. The type of ground truth used:

As explained above, the primary ground truth for AST devices is the reference broth microdilution (BMD) method as defined by recognized standards bodies (e.g., CLSI, EUCAST). In some cases, for specific resistance mechanisms, molecular methods (e.g., gene sequencing) might be used as confirmatory ground truth, or clinical outcomes data might support the relevance of the breakpoints.

8. The sample size for the training set:

For an AST device of this nature (lyophilized concentrations in microtiter panels), there isn't a "training set" in the AI/ML sense. The device's design and performance characteristics are based on established microbiological principles and in vitro studies carried out during its development. The "training" in this context would be the empirical optimization of the media formulation, drug concentrations, and well design during product development, which occurs prior to pivotal performance studies. This is not typically quantified in terms of a "sample size" like a machine learning training set.

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

Again, for this type of device, the "training set" and "ground truth" establishment are not applicable in the AI/ML sense. The reference method (BMD) is used throughout the development process to ensure the accuracy and reliability of the new device relative to the established gold standard. The development process involves iterative testing and refinement of the device's components and procedures against known bacterial isolates and their reference MICs.

Summary

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May 18, 2023

Liofilchem s.r.l. % Laura Koeth President Laboratory Specialists. Inc 26214 Center Ridge Road Westlake, Ohio 44145

Re: K230479

Trade/Device Name: ComASP Cefiderocol 0.008-128 Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: JWY, LTT Dated: February 21, 2023 Received: February 22, 2023

Dear Laura Koeth:

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

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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 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 (OS)

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 -S

Ribhi Shawar, Ph.D. (ABMM) 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

Enclosure

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Indications for Use

510(k) Number (if known) K230479

Device Name ComASP® Cefiderocol 0.008-128

Indications for Use (Describe)

Acinetobacter baumannii complex Escherichia coli Enterobacter cloacae complex Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa Serratia marcescens

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)	☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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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).