Liofilchem Antibiotic Discs are a semi-quantitative agar diffusion method for in vitro determination of antimicrobial susceptibility of clinical isolates tested on agar media after overnight incubation.

The Ceftobiprole BPR 5 µg Disc is intended to determine susceptibility of Enterobacterales and Staphylococcus aureus to ceftobiprole, as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC). Ceftobiprole at concentrations of 5 μg should be interpreted at 16-18 hours of incubation.

The Ceftobiprole BPR 5 µg Disc demonstrated acceptable performance with the following organisms:

Enterobacterales (Escherichia coli and Klebsiella pneumoniae)
Staphylococcus aureus (includes methicillin resistant isolates)

Device Description

Not Found

AI/ML Overview

Based on the provided FDA 510(k) Clearance Letter, the device in question is a "Ceftobiprole BPR 5 µg Disc." This is an Antimicrobial Susceptibility Test (AST) disc, not a medical imaging or AI-driven diagnostic device. Therefore, the acceptance criteria and study design elements typically associated with AI/ML-based devices (such as MRMC studies, multi-reader consensus, training/test sets for AI, pixel-level ground truth, etc.) are not applicable in this context.

The 510(k) letter discusses the substantial equivalence of this AST disc to legally marketed predicate devices. The "study" proving the device meets acceptance criteria for an AST disc involves demonstrating its performance in determining antimicrobial susceptibility for specific organisms, as recognized by FDA Susceptibility Test Interpretive Criteria (STIC).

Here's how to interpret the provided information in the context of an AST disc:

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

For an AST disc, "acceptance criteria" typically refer to the agreement of the new device's zone diameters or interpretations (Susceptible, Intermediate, Resistant) with a reference method (e.g., broth microdilution or another FDA-cleared AST method) and demonstrating acceptable categorical agreement (CA) and essential agreement (EA) rates, as well as addressing very major errors (VME), major errors (ME), and minor errors (mE). The specific numerical targets for these metrics are not provided in this 510(k) letter but are standard for AST device clearance.

The letter states:

Metric	Acceptance Criteria (Typical for AST)	Reported Device Performance
Performance Standard	Must demonstrate acceptable performance with specific organisms based on FDA Susceptibility Test Interpretive Criteria (STIC). This generally involves high rates of Categorical Agreement (CA) and Essential Agreement (EA) compared to a reference method, and low rates of very major, major, and minor errors.	"The Ceftobiprole BPR 5 µg Disc demonstrated acceptable performance with the following organisms:- Enterobacterales (Escherichia coli and Klebsiella pneumoniae)- Staphylococcus aureus (includes methicillin resistant isolates)" While specific percentages for CA, EA, VME, ME, mE are not in this letter, "acceptable performance" implies these standard metrics were met as per FDA guidance for AST devices.

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

Sample Size for Test Set: The 510(k) letter does not specify the number of isolates (sample size) used for the performance testing. For AST devices, this would typically be a pre-defined number of clinical isolates, often including a challenge set (e.g., resistant strains).
Data Provenance: The letter doesn't directly state the country of origin or if the study was retrospective or prospective. For AST studies, the isolates are usually collected from various clinical sources to ensure representativeness. They are often cultivated and tested prospectively in a lab setting.

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

For an AST disc, the "ground truth" is not established by human experts in the same way it is for image interpretation. Instead, the ground truth is established by a reference method, typically a CLSI-standardized broth microdilution method or another FDA-cleared AST system, using precisely controlled laboratory conditions.
The "experts" involved would be trained microbiologists and laboratory technicians who perform these standardized susceptibility tests accurately. Their qualification lies in their adherence to CLSI (Clinical and Laboratory Standards Institute) guidelines and good laboratory practices. The number of such individuals is not specified and is less relevant than the accuracy and standardization of the reference method itself.

4. Adjudication method for the test set:

Adjudication methods (e.g., 2+1, 3+1) are for subjective interpretations, primarily in medical imaging. For AST, the interpretations are quantitative (zone diameters) and then categorically assigned based on established breakpoints. There is no "adjudication" in the sense of multiple experts independently reviewing and then resolving discrepancies. The results from the test disc are compared directly to the results from the reference method.

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

No, an MRMC comparative effectiveness study was not done. MRMC studies are for evaluating human reader performance, often with and without AI assistance, especially in radiology. This is not applicable to an antimicrobial susceptibility test disc, which is a laboratory diagnostic tool that provides a direct measurement for interpretation.

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

This concept is also not applicable. The "device" is a physical disc that produces a zone of inhibition. A human (trained lab personnel) measures this zone and interprets it based on established criteria. There is no "algorithm" in the AI sense that performs a standalone diagnosis without human involvement. The interpretation is human-in-the-loop, though it's rule-based rather than expert opinion-based as in image reading.

7. The type of ground truth used:

The ground truth for an AST disc is typically established by comparison to a CLSI-standardized reference method, such as broth microdilution or agar dilution, or an existing FDA-cleared AST system with well-defined performance characteristics. The relevant outcome data is the in vitro susceptibility phenotype of the bacterial isolate. It is not expert consensus, pathology, or direct patient outcomes in this context, but rather highly controlled laboratory measurements.

8. The sample size for the training set:

For an AST disk like this, there isn't a "training set" in the AI/ML sense. The "training" of the device is through its precise manufacturing to consistently release the specified antimicrobial concentration and create reproducible inhibition zones. The "training data" for setting interpretive criteria (breakpoints) involves extensive in vitro testing of many strains, correlation with clinical outcomes, and pharmacokinetic/pharmacodynamic (PK/PD) studies, which often span decades of research. The 510(k) letter doesn't provide details on this broader historical "training" data.

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

As above, for an AST disc, the concept of a "training set" and "ground truth" establishment for it, as understood in AI/ML, doesn't directly apply. The establishment of ground truth for setting the specific concentration of the disc (5 µg) and the interpretive breakpoints (STIC) is a highly complex process within clinical microbiology. It involves:
- Extensive in vitro susceptibility testing: Using reference methods like broth microdilution against thousands of bacterial isolates to determine the minimal inhibitory concentrations (MICs).
- Pharmacokinetic/Pharmacodynamic (PK/PD) studies: To understand drug concentrations in the body and how they relate to the MICs needed to inhibit bacterial growth.
- Clinical Efficacy Data: Correlation between in vitro susceptibility results and patient outcomes in clinical trials (though these trials are usually for the drug itself, not the disc).
- Expert Consensus and Regulatory Body Review: Committees (like CLSI and FDA) review all the available data to establish and officially recognize Susceptibility Test Interpretive Criteria (STIC) or breakpoints.

In summary, the information in the 510(k) letter pertains to an Antimicrobial Susceptibility Test Disc, which follows a different regulatory and validation pathway than AI/ML-driven diagnostic devices. The details requested primarily apply to AI-based systems.

Summary

FDA 510(k) Clearance Letter

U.S. Food & Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov

Doc ID # 04017.07.05

June 23, 2025

Liofilchem Inc.
Emily Hodgkins
Microbiologist
465 Waverley Oakes Road
Suite 317
Waltham, Massachusetts 02452

Re: K250885
Trade/Device Name: Ceftobiprole BPR 5 µg Disc
Regulation Number: 21 CFR 866.1620
Regulation Name: Antimicrobial Susceptibility Test Disc
Regulatory Class: Class II
Product Code: JTN
Dated: March 12, 2025
Received: March 25, 2025

Dear Emily Hodgkins:

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.

FDA's substantial equivalence determination also included the review and clearance of your Predetermined Change Control Plan (PCCP). Under section 515C(b)(1) of the Act, a new premarket notification is not required for a change to a device cleared under section 510(k) of the Act, if such change is consistent with an established PCCP granted pursuant to section 515C(b)(2) of the Act. Under 21 CFR 807.81(a)(3), a new premarket notification is required if there is a major change or modification in the intended use of a device, or if there is a change or modification in a device that could significantly affect the safety or effectiveness of

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K250885 - Emily Hodgkins Page 2

the device, e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process. Accordingly, if deviations from the established PCCP result in a major change or modification in the intended use of the device, or result in a change or modification in the device that could significantly affect the safety or effectiveness of the device, then a new premarket notification would be required consistent with section 515C(b)(1) of the Act and 21 CFR 807.81(a)(3). Failure to submit such a premarket submission would constitute adulteration and misbranding under sections 501(f)(1)(B) and 502(o) of the Act, respectively.

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).

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 QS 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 (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-safety-reporting-combination-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 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.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

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-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems.

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K250885 - Emily Hodgkins Page 3

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-devices/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-devices/device-advice-comprehensive-regulatory-assistance/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)
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

Enclosure

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FORM FDA 3881 (8/23) Page 1 of 1

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

510(k) Number (if known)
K250885

Device Name
Ceftobiprole BPR 5 µg Disc

Indications for Use (Describe)

The Ceftobiprole BPR 5 µg Disc demonstrated acceptable performance with the following organisms:

Enterobacterales (Escherichia coli and Klebsiella pneumoniae)
Staphylococcus aureus (includes methicillin resistant isolates)

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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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).