(52 days)
Antimicrobial Susceptibility Test Disks are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Voriconazole 1ug BBL" Sensi-Disc " is intended for use in determining the susceptibility to Voriconazole of a wide range of pathogens, 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 21-266.
Use of Voriconazole 1μg, BBL™ Sensi-Disc™ for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of pathogens to Voriconazole. The concentration of 1 ug has been shown to be active in vitro against most strains of Candida species listed below, as described in the FDA approved drug insert for this agent.
Active In Vitro and in Clinical Infections Against:
Candida albicans Candida glabrata Candida krusei Candida parapsilosis Candida tropicalis
Active In Vitro Against:
Candida lusitaniae Candida guilliermondii
Voriconazole 1ug BBL™ Sensi-Disc™ is prepared by impregnating high quality paper with accurately determined amounts of Voriconazole supplied by the drug manufacturer. Each Voriconazole disk is clearly marked on both sides with the agent and drug content. Voriconazole 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. Voriconazole 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) summary does not contain a specific acceptance criteria table or a detailed study section with performance metrics in numerical form. The submission focuses on establishing substantial equivalence to a predicate device for the Voriconazole 1µg BBL™ Sensi-Disc™ Antimicrobial Susceptibility Test Disks. Instead, it references the Voriconazole drug package insert, "Susceptibility Testing Methods: Diffusion Techniques" (Appendix 1) as the source of substantial equivalence testing data, which is not included in the provided text.
However, based on the information provided, we can infer some aspects and highlight what is missing.
1. Table of Acceptance Criteria and Reported Device Performance
This information is not explicitly provided in the given 510(k) summary. 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 21-266." This implies that the acceptance criteria are existing standards (zone size ranges) from the FDA-approved drug insert for Voriconazole. The document does not present the specific zone sizes observed with the BBL™ Sensi-Disc™ Voriconazole 1 µg for various organisms.
Inferred Information:
| Metric | Acceptance Criteria (Inferred from Drug Insert/CLSI) | Reported Device Performance (Not explicitly stated in this document) |
|---|---|---|
| Zone Diameter | Specific zone size ranges (mm) for Susceptible (S), Susceptible-Dose Dependent (S-DD), and Resistant (R) categories for various Candida species (e.g., C. albicans, C. glabrata, etc.) | Actual zone diameters observed during testing (not provided) |
| Control Organism | Specific zone size limits for quality control strains | Actual zone diameters observed for control strains (not provided) |
| Categorical Agreement | Agreement with reference method (likely MIC) for S/S-DD/R classifications | Percentage agreement (not provided) |
2. Sample size used for the test set and the data provenance
- The document states that the testing data is in the "Voriconazole drug package insert, "Susceptibility Testing Methods: Diffusion Techniques" (Appendix 1)." This appendix is not provided.
- Therefore, the exact sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective) are not available in this submission.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- This information is not provided in the 510(k) summary. The ground truth for antimicrobial susceptibility testing typically comes from reference methods (like broth microdilution for Minimum Inhibitory Concentration - MIC), which are interpreted by trained laboratory personnel following standardized guidelines (e.g., CLSI). The involvement of "experts" in the sense of clinical specialists establishing grand truth is not typically applicable in this context.
4. Adjudication method for the test set
- This information is not provided. For antimicrobial susceptibility testing, interpretations are generally made by comparing measured zone diameters to established breakpoints (from CLSI or the drug insert), rather than through an adjudication process among human readers.
5. Multi-reader multi-case (MRMC) comparative effectiveness study
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted or reported in this 510(k) summary. This type of study is more common for diagnostic imaging or interpretation tasks where human readers' performance is being evaluated.
- The device (Antimicrobial Susceptibility Test Disk) is a semi-quantitative in vitro diagnostic device used to determine susceptibility, not a tool to assist human readers in interpreting complex cases. Therefore, the concept of "how much human readers improve with AI vs. without AI assistance" is not applicable to this type of device.
6. Standalone (i.e., algorithm only without human-in-the loop performance) study
- Yes, the device is designed for "standalone" performance in the sense that it provides a direct measurement (zone diameter) that is then interpreted based on established breakpoints. The "algorithm" here is the physical diffusion process and the subsequent measurement and comparison to predefined ranges. There isn't an "AI" algorithm in the modern sense.
- The "performance" of the device itself (accuracy of drug impregnation, consistency of disk manufacturing, correlation of zone size to MIC) would have been established in the studies cited in the Voriconazole drug package insert. The 510(k) focuses on the substantial equivalence of the disk format and concentration to existing devices.
7. Type of ground truth used
- The ground truth for antimicrobial susceptibility testing, which the BBL™ Sensi-Disc™ method correlates with, is typically Minimum Inhibitory Concentration (MIC) values determined by a reference method such as broth microdilution. These MIC values are then categorized into Susceptible (S), Susceptible-Dose Dependent (S-DD), or Resistant (R) based on established breakpoints.
- The document implies this by stating: "The categorical interpretation [susceptible (S), susceptible-dose dependent (S-DD), or resistant (R)] for the organism being tested is made by comparing zone diameters to those found in the approved pharmaceutical package insert." These interpretations in the package insert are derived from correlation with MIC data.
8. Sample size for the training set
- The 510(k) summary does not provide specific details about a "training set" in the context of machine learning. For traditional in vitro diagnostic devices like this, the "training" equivalent would be the extensive studies (spanning many years and numerous isolates) conducted to establish the correlation between zone diameters and MIC values, and to define the interpretive breakpoints for Voriconazole. This data would be part of the original drug's NDA (NDA 21-266).
- Therefore, the sample size for the training set is not available in this document.
9. How the ground truth for the training set was established
- As mentioned above, the "ground truth" for establishing the interpretive criteria (i.e., the "training set" for breakpoints) would have been established through correlation studies comparing zone diameters to Minimum Inhibitory Concentration (MIC) values obtained using a reference method (e.g., broth microdilution) across a large and diverse collection of clinical isolates. These studies would have been part of the original drug development and regulatory approval (NDA 21-266).
- These correlation studies aim to find the zone diameter breakpoints that best predict the MIC-based susceptibility categories (S, S-DD, R).
§ 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).