(172 days)
The MicroScan Dried Gram-Negative MIC/Combo Panel is used to determine quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/ - 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert.
This particular submission is for the addition of the reformulated antimicrobial imipenem at concentrations of 0.25 to 8 ug/ml to the test panel.
The gram-negative organisms which may be used for imipenem susceptibility testing in this panel are:
Acinetobacter spp. Citrobacter spp. Escherichia coli, Klebsiella spp. Morganella morganii, Proteus vulgaris, Providencia rettgeri, and Pseudomonas aeruginosa
MicroScan Dried Gram-Negative MIC/Combo Panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-neqative bacilli.
The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.
This document is a 510(k) premarket notification for a medical device: the MicroScan Dried Gram-Negative MIC/Combo Panels with Imipenem. This type of document is filed with the FDA to demonstrate that a device is substantially equivalent to a legally marketed predicate device, rather than requiring full PMA approval. Therefore, the "study" described herein is a validation study comparing the new device to a reference method, rather than a clinical trial assessing a new drug or treatment.
Here's an analysis of the provided text to extract the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
| Metric | Acceptance Criteria (from "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", dated August 28, 2009) | Reported Device Performance (MicroScan Dried Gram-Negative MIC/Combo Panel with Imipenem) |
|---|---|---|
| Overall Essential Agreement (compared to CLSI frozen Reference Panel) | Not explicitly stated in the provided text as a numerical acceptance criterion, but the context implies "acceptable performance" as defined by the guidance document. | 95.5% |
| Inoculum and Instrument Reproducibility | Not explicitly stated as a numerical acceptance criterion in the provided text, but the context implies "acceptable reproducibility and precision." | Demonstrated acceptable reproducibility and precision. |
| Quality Control (QC) Testing | Not explicitly stated as a numerical acceptance criterion in the provided text, but the context implies "acceptable results." | Demonstrated acceptable results. |
Explanation of "Essential Agreement": In antimicrobial susceptibility testing, Essential Agreement (EA) typically means that the MIC (Minimum Inhibitory Concentration) results from the test device are within +/- one doubling dilution of the reference method's MIC.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: The document does not explicitly state the total number of isolates (samples) used in the "external evaluations." It mentions "fresh and stock Efficacy isolates and stock Challenge strains."
- Data Provenance: Not explicitly stated (e.g., country of origin). The study involved "external evaluations," which could imply multi-center or independent lab testing, but no specific locations are mentioned. The data is retrospective, as it uses "stock" isolates and challenge strains.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts
- This information is not provided in the document. The ground truth for susceptibility testing is established by the CLSI (Clinical and Laboratory Standards Institute) frozen Reference Panel, which represents a standardized and accepted method, not typically by human expert consensus in the same way a diagnostic imaging study would be.
4. Adjudication Method for the Test Set
- This is not applicable in the context of antimicrobial susceptibility testing where the "ground truth" is determined by a reference laboratory method (CLSI frozen Reference Panel), rather than human interpretation requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
- No, an MRMC study was not done. This type of study is relevant for diagnostic imaging interpretation where human readers interpret images. For an AST device, the comparison is against a reference laboratory method.
- Effect Size of Human Readers Improvement: Not applicable as no MRMC study was conducted. However, the document does imply human involvement in reading results (visually or with MicroScan instrumentation) after incubation. The study validated the device's performance in generating the MIC, not the human interpretation of that MIC.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done
- Yes, effectively. While the device can be read visually, the core validation is of the device's ability to produce an accurate MIC result when compared to the CLSI reference method. The "MicroScan instrumentation" option for reading implies algorithmic interpretation. The study evaluates the panel's performance as a standalone system for determining antimicrobial susceptibility, regardless of the reading method. The reproducibility testing confirms the device's consistent performance.
7. The Type of Ground Truth Used
- The ground truth used was the CLSI frozen Reference Panel. This is a recognized standard method for antimicrobial susceptibility testing, providing a highly reliable and standardized reference for MIC values. It's akin to a "gold standard" laboratory method.
8. The Sample Size for the Training Set
- This information is not provided in the document. For a 510(k) for an AST device, the "training set" doesn't typically refer to a machine learning training dataset. Instead, it would refer to the development and internal validation data used during the device's creation. The provided document focuses on the final validation study for regulatory submission.
9. How the Ground Truth for the Training Set Was Established
- This information is not provided in the document. As noted above, the concept of a "training set" with ground truth in the machine learning sense is likely not applicable here in the way it would be for an AI/ML-based diagnostic device. The development of an AST panel involves optimizing the concentrations and formulation to ensure accurate results, which would rely on established microbiological methods and internal testing, analogous to how the final validation ground truth (CLSI reference) is established.
§ 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).