(225 days)
To determine gram-negative and gram-positive bacterial susceptibility against the antimicrobial agent Cefdinir.
Organisms with indications for testing* include:
Gram-Negative Bacteria: None**
Gram-Positive Bacteria: Staphylococcus aureus *** (Including methicillin-susceptible, β-lactamase producing strains), Streptococcus pyogenes
*As taken from the indications and Usage section of the manufacturer's package insert (Issued: March 1998).
**No gram-negative organisms for which Microscan is seeking clearance are indicated for testing in the Indications and Usage section of the manufacturer's package insert.
***Cefdinir is inactive against methicillin-resistant Staphylococcus
The following secondary organisms included for the testing of MicroScan® panels with Cefdinir have in vitro data but the safety and effectiveness in treating clinical infections have not been established: Citrobacter (diversus) koseri, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus epidermidis (methicillin-susceptible), Streptococcus agalactiae
Microdilution Minimum Inhibitory Concentration (MIC) Panels, specifically MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels with Cefdinir.
Here's an analysis of the provided text, focusing on the acceptance criteria and study details for the MicroScan® Dried Gram-Negative and Gram-Positive MIC/Combo Panels with Cefdinir:
The document describes the regulatory submission (510(k)) for a new antimicrobial agent, Cefdinir, to be used with MicroScan MIC (Minimum Inhibitory Concentration) panels. The study aims to demonstrate that the performance of these new panels is substantially equivalent to a legally marketed predicate device, the NCCLS Frozen Cefdinir Reference Panels.
1. Table of Acceptance Criteria and Reported Device Performance
Acceptance Criteria for Essential Agreement (Based on FDA DRAFT document "Review Criteria for Assessment of Antimicrobial Susceptibility Devices" dated May 31, 1991): While the exact numerical acceptance criteria are not explicitly stated within this document fragment, it is implied that an "acceptable performance" is defined by Essential Agreement. Based on similar FDA guidances for antimicrobial susceptibility testing devices, an Essential Agreement (EA) of ≥ 90% and/or ≥ 95% is typically required for new antimicrobial-device combinations. Given the reported performance, the presumed acceptance criterion for Essential Agreement would be in this range.
| Metric | Acceptance Criteria (Implied) | Reported Device Performance (Gram-Negative) | Reported Device Performance (Gram-Positive) |
|---|---|---|---|
| Essential Agreement | Acceptable Performance (e.g., ≥ 90-95%) | 97.9% | 94.0% |
| Reproducibility | Acceptable Reproducibility | Acceptable | Acceptable |
| Precision | Acceptable Precision | Acceptable | Acceptable |
| Quality Control | Acceptable Performance | Acceptable | Acceptable |
Notes on Essential Agreement: Essential Agreement refers to agreement between the MIC values of the test device and the reference method within a specified range (typically ±1 doubling dilution).
2. Sample Size and Data Provenance
- Test Set Sample Size: The exact number of isolates (sample size) for the external evaluations is not explicitly stated in the provided text. It mentions "fresh and stock Efficacy isolates and stock Challenge strains" were used.
- Data Provenance: The studies were described as "external evaluations," implying they were conducted at sites outside the manufacturer's primary facility. The country of origin is not specified, but given the manufacturer (Dade MicroScan Inc., located in West Sacramento, CA) and the FDA submission, it is highly likely the evaluations were conducted in the United States. The data is prospective, as it was generated specifically for this 510(k) submission to compare the new device against a reference.
3. Number of Experts and Qualifications for Ground Truth
- The document does not explicitly mention the number of experts or their specific qualifications (e.g., years of experience) used to establish the ground truth for the test set.
- The ground truth was established by the NCCLS Frozen Cefdinir Reference Panel. This implies that the 'experts' would be the individuals or laboratories meticulously performing and interpreting the reference method according to NCCLS (now CLSI) guidelines, which are established by consensus among microbiologists and clinicians.
4. Adjudication Method for the Test Set
- The document does not specify an explicit adjudication method (e.g., 2+1, 3+1). The comparison is described as a direct performance comparison (Essential Agreement) between the MicroScan device and the NCCLS reference panel. Any discrepancies would typically be resolved by retesting or further analysis in accordance with standard microbiology practices for AST performance studies, though this is not detailed.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed or described for this device. This type of study is more common in imaging diagnostics where human interpretation is a primary component of the diagnostic workflow. For automated microbiology susceptibility testing panels, the focus is on the agreement of the device's output (MIC values) with a gold standard, rather than how human readers' performance is affected by the device.
6. Standalone Performance Study
- Yes, a standalone performance study was done. The reported Essential Agreement (97.9% for gram-negative and 94.0% for gram-positive) directly reflects the algorithm-only/device-only performance of the MicroScan panels when compared to the NCCLS reference method. There is no mention of a human-in-the-loop component for interpreting the raw results beyond what is standard for any AST device (e.g., technician reading a panel, entering data, etc.). The study evaluated the device's ability to accurately determine MIC values on its own.
7. Type of Ground Truth Used
- The ground truth used was expert consensus / reference method. Specifically, the "NCCLS Frozen Cefdinir Reference Panel" served as the gold standard. NCCLS (National Committee for Clinical Laboratory Standards, now CLSI) methods are widely regarded as the gold standard for antimicrobial susceptibility testing, representing a consensus of expert microbiological and clinical knowledge.
8. Sample Size for the Training Set
- The document does not provide any information regarding a "training set" or its sample size. This is typical for a device like this, which likely uses a pre-defined algorithm and interpretive rules for MIC determination rather than a machine learning model that requires a dedicated training phase with labeled data. The development of the panel itself (e.g., concentrations of antimicrobials) would be based on extensive prior knowledge and calibration, but not in the sense of a machine learning "training set."
9. How the Ground Truth for the Training Set was Established
- As no training set is described or implied for a machine learning context, the method for establishing its ground truth is not applicable here. The overall "training" for such a device relies on established microbiological principles, extensive historical data on drug-bug interactions, and adherence to reference methods (like those from NCCLS/CLSI) during its development and validation.
§ 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).