(170 days)
The BD MAX™ MRSA Assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection of Methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of MRSA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The BD MAX™ MRSA Assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. It is not intended to diagnose, guide or monitor MRSA infections. A negative result does not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.
The BD MAX™ MRSA Assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection of Methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of MRSA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The assay also includes a Sample Processing Control (SPC). The Sample Processing Control is present in the Extraction Tube and undergoes the extraction and amplification steps to monitor for inhibitory substances as well as process inefficiency due to instrument or reagent failure. No operator intervention is necessary once the clinical sample and reagent strip are loaded into the BD MAX™ System. The BD MAX™ System automates sample lysis, DNA extraction and concentration, reagent rehydration, nucleic acid amplification and detection of the target nucleic acid sequence using real-time polymerase chain reaction (PCR). Amplified targets are detected with hydrolysis probes labeled with quenched fluorophores. The amplification, detection and interpretation of the signals are done automatically by the BD MAX™ System.
The BD MAX™ System uses a combination of lytic and extraction reagents to perform cell lysis and DNA extraction. Following enzymatic cell lysis at elevated temperature, the released nucleic acids are captured by magnetic affinity beads. The beads with the bound nucleic acids are washed and the nucleic acids are eluted by heat in Elution Buffer. Eluted DNA is neutralized with Neutralization Buffer and transferred to the Master Mix Tube to rehydrate PCR reagents. The reconstituted amplification reagent is dispensed into the BD MAX™ PCR Cartridge. Microvalves in the BD MAX™ PCR Cartridge are sealed by the system prior to initiating PCR to prevent evaporation and amplicon contamination.
The amplified DNA targets are detected using hydrolysis (TagMan®) probes labeled at one end with a fluorescent reporter dye (fluorophore) and at the other end with a quencher moiety. Probes labeled with different fluorophores are used to detect MRSA and SPC amplicons in two different optical channels of the BD MAX™ System: MRSA amplicons are detected in the FAM channel and SPC amplicons are detected in the ROX channel. When the probes are in their native state, the fluorescence of the fluorophore is quenched due to its proximity to the quencher. However, in the presence of target DNA, the probes hybridize to their complementary sequences and are hydrolyzed by the 5'-3' exonuclease activity of the DNA polymerase as it synthesizes the nascent strand along the DNA template. As a result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The amount of fluorescence detected in the two optical channels used for the BD MAX™ MRSA Assay is directly proportional to the quantity of the corresponding probe that is hydrolyzed. The BD MAX™ System measures these signals at the end of each amplification cycle, and interprets the data to provide a result.
1. Acceptance Criteria and Device Performance:
The acceptance criteria are not explicitly stated as numerical thresholds in the provided document. However, the study aims to demonstrate substantial equivalence to the predicate device (BD GeneOhm™ MRSA ACP Assay) based on the presented sensitivity and specificity values. Therefore, the device's performance metrics serve as the "reported device performance" against an implied standard of clinical utility and equivalence.
| Metric | Reported Device Performance (BD MAX™ MRSA Assay) | Implied Acceptance Criteria (Based on Substantial Equivalence) |
|---|---|---|
| Overall Sensitivity | 93.0% (146/157) (87.9%, 96.0% CI) | High sensitivity to detect MRSA, comparable to predicate |
| Overall Specificity | 95.9% (1653/1724) (94.8%, 96.7% CI) | High specificity to correctly identify absence of MRSA, comparable to predicate |
| Initial Unresolved Rates | 0.5% (10/1884) (0.3%, 1.0% CI) | Low unresolved rate |
| Unresolved Rates After Repeat | 0.0% (0/1882) (0.0%, 0.2% CI) | Very low to zero unresolved rate after repeat testing |
2. Sample Size and Data Provenance for the Test Set:
- Sample Size:
- Clinical Performance (Reference Method): 1903 specimens were reference method compliant (Table 2, footnote 3).
- Comparison to Direct Culture: 1881 specimens (Table 3).
- Unresolved Rates: 1884 specimens were PCR method compliant for initial rates, and 1882 for rates after repeat (Table 5, footnote 2).
- Data Provenance:
- Country of Origin: Not explicitly stated, but the submission is from GeneOhm Sciences Canada Inc. (BD Diagnostics) and the FDA approval is from the US. The study involved "multi-site prospective investigational study" with "Four (4) investigational centers participated," suggesting US or North American data.
- Retrospective or Prospective: Prospective. The document states: "Clinical performance characteristics of the BD MAX™ MRSA Assay were determined in a multi-site prospective investigational study."
3. Number of Experts and Qualifications for Ground Truth:
The document does not mention the use of human experts to establish the ground truth in the traditional sense of consensus reading for diagnostic imaging or clinical assessment.
- Ground Truth Method: The "Comparative Reference Method" used a laboratory-based process: direct culture complemented by enriched culture. The identification of S. aureus was confirmed with an agglutination test, and Methicillin-resistance was confirmed by Cefoxitin disk diffusion susceptibility testing. No human experts are described as providing subjective interpretations for ground truth.
4. Adjudication Method for the Test Set:
Not applicable. The ground truth was established through objective laboratory culture and susceptibility testing, not through expert consensus or a process that would require adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, an MRMC comparative effectiveness study was not done. This device is an automated, in vitro diagnostic molecular assay (PCR-based), not an imaging or clinical interpretation tool that relies on human readers. Therefore, the concept of human readers improving with or without AI assistance does not apply in this context.
6. Standalone Performance Study:
- Yes, a standalone study was performed. The entire clinical performance section (Tables 1-5) details the performance of the BD MAX™ MRSA Assay (the algorithm/device only) compared to a defined reference method. This is a direct measure of the algorithm's performance without human intervention in result interpretation. The "amplification, detection and interpretation of the signals are done automatically by the BD MAX™ System."
7. Type of Ground Truth Used:
- Laboratory Reference Method: The ground truth was established using a "Comparative Reference Method" which consisted of direct culture complemented by enriched culture. This involved:
- Presumptive S. aureus colonies on selective media.
- Subculture onto Blood Agar (BA).
- Identification confirmed with an agglutination test.
- Methicillin-resistance confirmed by Cefoxitin disk (30μg) diffusion susceptibility testing.
- Enrichment in Trypticase Soy Broth with 6.5% NaCl (TSB 6.5% NaCl) for initial direct culture-negative specimens, followed by re-inoculation and MRSA confirmation as above.
8. Sample Size for the Training Set:
- The document does not provide information on the sample size used for the training set. This submission focuses on the performance of the final device in a clinical validation study rather than the development process.
9. How Ground Truth for the Training Set Was Established:
- The document does not provide information on how the ground truth for the training set was established. As mentioned above, the focus is on the validation study, not the development data.
§ 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).