(260 days)
The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System is an in vitro diagnostic product for clinical susceptibility testing of non-fastidious isolates.
This 510(k) is for vancomycin in the dilution range of 0.25-128 ug/mL for testing non-fastidious gram-positive isolates on the Sensititre 18-24 hour MIC or Breakpoint Susceptibility System. Testing is indicated for Staphylococcus aureus, Staphylococci other than Staphylococcus aureus, and Enterococcus spp., as recognized by the FDA Susceptibility Test Interpretive Criteria (STIC) webpage.
The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin in the dilution range of 0.25-128 ug/mL demonstrated acceptable performance with the following organisms:
Staphylococcus aureus (including MRSA)
Staphylococci other than Staphylococcus aureus (S. epidermidis, S. haemolyticus, S. hominis, S. lugdunensis, S. saprophyticus)
Enterococcus spp. (E. faecalis, E. faecium)
Not Found
The provided FDA 510(k) clearance letter pertains to an Antimicrobial Susceptibility Test (AST) System (The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin). This type of medical device is designed to determine the susceptibility of bacteria to various antimicrobial agents.
It's crucial to understand that the information typically requested in your prompt (especially regarding AI/ML models, MRMC studies, expert consensus on ground truth for medical images, etc.) is NOT APPLICABLE to this type of device. The FDA clearance letter describes a traditional in vitro diagnostic product, not a software-as-a-medical-device (SaMD) or an AI/ML-powered diagnostic aid.
Therefore, the following points address the questions to the extent they are relevant to a traditional AST system, while clarifying where the requested information is not applicable.
Description of Acceptance Criteria and Study Proving Device Performance for The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin
This device is an in vitro diagnostic product used for clinical susceptibility testing of non-fastidious bacterial isolates against Vancomycin. The performance of such systems is typically evaluated based on their ability to accurately determine the Minimum Inhibitory Concentration (MIC) or breakpoint susceptibility, which is compared to a reference method.
1. Table of Acceptance Criteria and Reported Device Performance
For Antimicrobial Susceptibility Test (AST) systems, acceptance criteria are generally based on agreement rates with a reference method (e.g., broth microdilution or agar dilution as per CLSI standards). The key performance metrics are:
- Essential Agreement (EA): The MIC result obtained by the test device is within ±1 doubling dilution of the reference method MIC.
- Categorical Agreement (CA): The interpretation (Susceptible, Intermediate, Resistant) obtained by the test device agrees with the interpretation from the reference method.
- Minor Errors (mE): The test device classifies a sample as Susceptible when the reference method classifies it as Intermediate or Resistant, or as Intermediate when the reference method classifies it as Susceptible or Resistant.
- Major Errors (ME): The test device classifies a sample as Resistant when the reference method classifies it as Susceptible.
- Very Major Errors (VME): The test device classifies a sample as Susceptible when the reference method classifies it as Resistant.
Typical Acceptance Criteria (General for AST, specific values are submission-dependent):
| Performance Metric | Acceptance Criteria (General) | Reported Device Performance (Not explicitly stated in the letter, but implied for clearance) |
|---|---|---|
| Essential Agreement (EA) | ≥ 90-95% (e.g., typically ≥ 90% for clinical isolates) | Implied to be met for clearance |
| Categorical Agreement (CA) | ≥ 90-95% (e.g., typically ≥ 90% for clinical isolates) | Implied to be met for clearance |
| Minor Errors (mE) | ≤ 10% | Implied to be within acceptable limits |
| Major Errors (ME) | ≤ 3% | Implied to be within acceptable limits |
| Very Major Errors (VME) | ≤ 1.5% (especially for critical drugs like Vancomycin) | Implied to be within acceptable limits |
The clearance letter states: "The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin in the dilution range of 0.25-128 µg/mL demonstrated acceptable performance with the following organisms: Staphylococcus aureus (including MRSA), Staphylococci other than Staphylococcus aureus (S. epidermidis, S. haemolyticus, S. hominis, S. lugdunensis, S. saprophyticus), Enterococcus spp. (E. faecalis, E. faecium)." This statement confirms that the specific performance criteria (EA, CA, mE, ME, VME) were met for these organisms, although the exact percentages are not provided in the public clearance letter.
2. Sample Size Used for the Test Set and Data Provenance
The clearance letter does not specify the exact sample size used for the test set. For AST systems, the test set typically includes a significant number of clinical isolates (hundreds to thousands, often including challenge strains with known resistance mechanisms) to ensure robustness across various resistance profiles.
- Data Provenance: For in vitro diagnostic devices, data is typically collected from prospective and/or retrospective clinical samples from laboratories, often from multiple geographically diverse sites within the country of submission (e.g., the United States for FDA clearance) to represent real-world clinical populations. Some isolates may also come from culture collections.
3. Number of Experts Used to Establish Ground Truth and Qualifications
This question is not applicable in the context of an AST system being cleared.
- Ground truth for AST systems is established by validated reference methods (e.g., CLSI broth microdilution, agar dilution, or molecular methods for specific resistance genes) run by trained laboratory personnel, not by expert interpretation of images or clinical data. There are no "experts" in the sense of physicians or radiologists reviewing and labeling data.
4. Adjudication Method for the Test Set
This question is not applicable.
- Since ground truth is established by a quantitative laboratory method, there is no "adjudication" in the sense of multiple human readers resolving disagreements. Discrepancies between the test device and the reference method would be analyzed, and repeated testing or further characterization of the isolate might occur if needed during the study design, but it's not a consensus-based adjudication process.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size
This question is not applicable.
- MRMC studies are relevant for devices that involve human interpretation of medical images or complex data (e.g., AI-powered CADe/CADx devices for radiology). An AST system is an automated or semi-automated laboratory instrument that provides a direct result (MIC value, interpretation) based on bacterial growth or lack thereof. There is no "human reader" component in the direct output of the device that would be assisted by AI, nor is there a direct human comparative effectiveness study for its primary function.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
This question is not applicable in the sense of an AI algorithm.
- The Sensititre 18-24 hour system is primarily a "standalone" device in that it produces susceptibility results without requiring human "interpretation" of a complex output like an image. Its performance is evaluated independently against a reference method. However, it's not an "algorithm only" in the sense of a software-driven AI solution; it is a laboratory instrument that performs a specific biological assay.
7. The Type of Ground Truth Used
- The ground truth for AST systems is based on reference antimicrobial susceptibility testing methods, typically broth microdilution or agar dilution as per a recognized standard (e.g., Clinical and Laboratory Standards Institute - CLSI guidelines). This is considered the "gold standard" for determining MIC values and categorical interpretations. In some cases, molecular methods (e.g., PCR for resistance genes) might be used to confirm certain resistance mechanisms, which indirectly supports the "ground truth" for specific resistant phenotypes.
8. The Sample Size for the Training Set
This question is not applicable for a traditional AST system.
- Traditional AST systems are not "trained" in the way AI/ML models are. They are designed and validated based on established microbiological principles. There is no distinct "training set" of data used to iteratively improve an algorithm's performance. Instead, the device is developed, and its performance is then validated against a large test set to ensure accuracy and reproducibility.
9. How the Ground Truth for the Training Set was Established
This question is not applicable for a traditional AST system, as there is no "training set" in the AI/ML sense.
In summary, the FDA clearance for The Sensititre 18-24 hour MIC or Breakpoint Susceptibility System with Vancomycin is based on the device's ability to accurately determine antimicrobial susceptibility by comparing its results to established reference methods using a statistically significant number of relevant bacterial isolates. The concepts of AI/ML model training, human expert consensus for image interpretation, and MRMC studies are not relevant to the validation of this traditional in vitro diagnostic device.
§ 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).