(35 days)
Antimicrobial Susceptibility Test Disks are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Doripenem 10ug BBL™ Sensi-Disc™ is intended for use in determining the susceptibility to Doripenem of a wide range of bacteria, as described in the "Indications for Use" section. Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer and received FDA approval under NDA Number 22-106.
Use of Doripenem 10µg BBL" Sensi-Disc" for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Doripenem. The concentration of 10ug has been shown to be active in viro against most strains of microorganisms listed below, as described in the FDA approved drug insert for this antimicrobic.
Active In Vitro and in Clinical Infections Against:
Aerobic facultative Gram-positive microorganisms Streptococcus constellatus Streptococcus intermedius
Aerobic and facultative Gram-negative microorganisms Acinetobacter baumannii Escherichia coli Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa
Active In Vitro Against:
Aerobic and facultative Gram-positive microorganisms Staphylococcus aureus - (methicillin-susceptible isolates only) Streptococcus agalactiae Streptococcus pyogenes
Aerobic and facultative Gram-negative microorganisms Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Klebsiella oxytoca Morganella morganii Serratia marcescens
Doripenem10µg BBL™ Sensi-Disc" is prepared by impregnating high quality paper with accurately determined amounts of Doripenem supplied by the drug manufacturer. Each Doripenem disk is clearly marked on both sides with the agent and drug content. Doripenem cartridges each contain 50 impregnated disks that are packed as either a single cartridge in a single box, or in a package containing ten cartridges. Doripenem disks are used for semi-quantitative in vitro susceptibility evaluations by the agar diffusion test method.
Agar diffusion susceptibility methods employing dried filter paper disks impregnated with specific concentrations of antimicrobial agents were developed in the 1940s. In order to eliminate or minimize variability in the testing, Bauer et al. developed a standardized procedure in which Mueller Hinton Agar was selected as the test medium.
Various regulatory agencies and standards-writing organizations subsequently published standardized reference procedures based on the Bauer-Kirby method. Among the earliest and most widely accepted of these standardized procedures were those published by the U.S. Food and Drug Administration (FDA) and the World Health Organization (WHO). The procedure was adopted as a consensus standard by the Clinical and Laboratory Standards Institute (CLSI) [Formerly National Committee for Clinical Laboratory Standards (NCCLS)] and is periodically updated.
The provided 510(k) submission describes the "Doripenem 10µg, BBL™ Sensi-Disc™ Antimicrobial Susceptibility Test Disks." This device is a semi-quantitative in vitro diagnostic tool used to determine the susceptibility of bacteria to Doripenem using standardized agar diffusion test procedures.
Here's an analysis of the acceptance criteria and the study information based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document states that "Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer and received FDA approval under NDA Number 22-106." It also mentions that "the categorical interpretation [susceptible (S), intermediate (I), or resistant (R)] for the organism being tested with the antimicrobial agent is made by comparing zone diameters to those found in the respective organism tables of CLSI/NCCLS Document M2 ("Performance Standards for Antimicrobial Disk Susceptibility Tests) and of CLSI/NCCLS Document M100 ("Performance Standards for Antimicrobial Susceptibility Testing")."
However, the specific numerical acceptance criteria (e.g., minimum percentage agreement with a reference method) and the performance data for the Doripenem 10µg Sensi-Disc obtained during the 510(k) submission process are not explicitly detailed in the provided text. The document refers to an "Appendix I - Doripenem drug package insert, 'Susceptibility Test Methods: Diffusion Techniques'" for "SUBSTANTIAL EQUIVALENCE TESTING DATA," but this appendix is not included in the provided text.
Based on the information available, the acceptance criteria are implicitly tied to the performance standards set by CLSI/NCCLS documents M2 and M100, and the FDA-approved drug insert for Doripenem (NDA 22-106). Without the performance data from that insert, a specific table of acceptance criteria vs. reported performance cannot be generated directly from this document.
2. Sample size used for the test set and the data provenance
The document states, "See the Doripenem drug package insert, 'Susceptibility Test Methods: Diffusion Techniques' (Appendix I)." This appendix would contain the details about the test set used for substantial equivalence testing. Without Appendix I, the exact sample size for the test set and the data provenance (e.g., country of origin, retrospective/prospective) cannot be determined from the provided text.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
Not explicitly mentioned in the provided text. Ground truth for antimicrobial susceptibility testing typically involves comparison to a reference method, such as broth microdilution or agar dilution, which are established laboratory procedures rather than expert consensus on individual cases.
4. Adjudication method for the test set
Not applicable in the context of antimicrobial susceptibility testing device validation as described. The "ground truth" is typically established by a reference laboratory method, not by human adjudication of images or clinical cases.
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 Antimicrobial Susceptibility Test Disk, a physical diagnostic tool for laboratory use, not an AI-assisted diagnostic imaging or clinical decision-support system involving human readers interpreting outputs for case diagnosis.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This device is not an algorithm. It is a physical disk impregnated with an antimicrobial agent. Its performance is evaluated in a standalone manner in the sense that the zone of inhibition measurement is a direct output, but human operators are involved in setting up the test, measuring the zones, and interpreting the results according to established guidelines (CLSI/NCCLS). The "algorithm" here would be the interpretative rules from CLSI/NCCLS. The performance data would represent the device's inherent capability to produce inhibition zones that correlate with bacterial susceptibility.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for evaluating Antimicrobial Susceptibility Test Disks is typically established by reference antimicrobial susceptibility testing methods, such as broth microdilution or agar dilution minimum inhibitory concentration (MIC) testing. The zone diameters obtained with the Sensi-Disc are then correlated with these MIC values to determine susceptibility categories (S, I, R). The document refers to "zone sizes... determined by the antimicrobic manufacturer and received FDA approval under NDA Number 22-106" and comparison to CLSI/NCCLS M2 and M100 documents. This implies that the ground truth is based on established laboratory standards and correlation with clinical outcomes data from the drug's development.
8. The sample size for the training set
Not explicitly mentioned in the provided text. The development of zone diameter breakpoints (which would implicitly constitute a "training" or "calibration" phase) for new antimicrobial agents typically involves extensive studies with a large and diverse collection of bacterial isolates by the drug manufacturer and standard-setting organizations. The document states "Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer and received FDA approval under NDA Number 22-106," indicating that the "training" was part of the drug development and approval process.
9. How the ground truth for the training set was established
The ground truth for establishing the zone diameter breakpoints (which can be considered analogous to a "training set" in this context) would have been established by the drug manufacturer as part of the new drug application (NDA 22-106). This process typically involves:
- Correlation studies: Comparing zone diameters obtained by the disk diffusion method with Minimum Inhibitory Concentrations (MICs) obtained using a reference method (e.g., broth microdilution or agar dilution) for a large number of diverse bacterial isolates.
- Pharmacokinetic/Pharmacodynamic (PK/PD) data: Integrating drug concentration profiles in the body with the MICs to predict clinical efficacy.
- Clinical outcome data: Correlating microbiologic susceptibility results with patient outcomes from clinical trials to define clinically relevant breakpoints (S, I, R).
- Expert committees (e.g., CLSI): Reviewing all available data to establish and periodically update breakpoints for various antimicrobial agents and bacterial species.
The provided document specifically refers to "FDA approved drug insert for this antimicrobic" and CLSI/NCCLS documents, confirming this multi-faceted approach to ground truth establishment for the interpretation criteria.
§ 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).