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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.

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.

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The BD GeneOhm™ StaphSR Assay is a qualitative in vitro diagnostic test for the rapid detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from positive blood culture. The assay utilizes polymerase chain reaction (PCR) for the amplification of specific targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed on Gram positive cocci, identified by Gram stain, from positive blood cultures. The BD GeneOhm™ StaphSR Assay is not intended to monitor treatment for MRSA/SA infections. Subculturing of positive blood cultures is necessary for further susceptibility testing.

The BD GeneOhm™ StaphSR Assay is a qualitative in vitro diagnostic test for the rapid detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from positive blood culture. The assay utilizes polymerase chain reaction (PCR) for the amplification of specific targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed on Gram positive cocci, identified by Gram stain, from positive blood cultures. To test a positive blood culture, an aliquot of the culture media is transferred into a sample buffer tube and lysed. Following specimen lysis, amplification of the targets (MRSA: a S. aureus specific target and a sequence near the insertion site of the Staphylococcal Cassette Chromosome mec (SCCmec); SA: another S. aureus specific sequence] occurs in the presence of either or both targets. Amplification of the IC, a DNA fragment of 335-bp including a 277-bp sequence not found in S. aureus or MRSA, also takes place unless PCR inhibitory substances are present. The amplified DNA targets are detected with molecular beacon probes, hairpin-forming single-stranded oligonucleotides labelled at one end with a quencher and at the other end with a fluorescent reporter dye (fluorophore). In the absence of target, the fluorescence is quenched. In the presence of target, the hairpin structure opens upon beacon/target hybridization, resulting in emission of fluorescence. For the detection of MRSA amplicon, the molecular beacon probe contains the fluorophore FAM at the 5' end and the non-fluorescent quencher moiety DABCYL at the opposite end of the oligonucleotide. For the detection of S. aureus amplicon, the molecular beacon probe is labelled with the fluorophore TexasRed at the 5' end and the quencher DABCYL at the 3' end. For the detection of the IC amplicon, the molecular beacon probe contains the fluorophore TET at the 5' end and the quencher DABCYL at the 3' end, Each beacon-target hybrid fluoresces at a wavelength characteristic of the fluorophore used in the particular molecular beacon probe. The amount of fluorescence at any given cycle, or following cycling, depends on the amount of specific amplicon present at that time. The SmartCycler software simultaneously monitors the fluorescence emitted by each beacon probe, interprets all data, and provides a final result at the end of the cycling program.

Acceptance Criteria and Device Performance for BD GeneOhm™ StaphSR Assay

This document describes the acceptance criteria and study proving the BD GeneOhm™ StaphSR Assay meets these criteria, as presented in the 510(k) Summary K071026.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the BD GeneOhm™ StaphSR Assay are implicitly established through the comparison to predicate devices, where the assay is deemed "substantially equivalent in performance." While specific numerical performance targets are not explicitly stated as "acceptance criteria" in the provided text, the clinical trial results demonstrate the performance achieved. Based on the analysis of the provided tables, the reported device performance for both MRSA and S. aureus detection consistently achieves high levels of positive and negative agreement with reference methods across multiple sites.

Note: The "acceptance criteria" are implied by the claim of "substantial equivalence in performance" to established predicate devices (Remel Staphaurex Latex Agglutination Test, BBL (BD) Oxacillin Screen Agar, and BD Phoenix Automated ID/AST System). The reported device performance demonstrates a high degree of concordance with these reference methods.

2. Sample Size Used for the Test Set and Data Provenance

The clinical trials were performed at five sites. The total sample sizes for the test set across all sites are calculated from the provided tables:

• For MRSA:
  • Site 1: 446 samples
  • Site 2: 133 samples
  • Site 3: 232 samples
  • Site 4: 286 samples
  • Site 5: 86 samples
  • Total MRSA Test Set: 1183 samples
• For S. aureus:
  • Site 1: 446 samples
  • Site 2: 133 samples
  • Site 3: 232 samples
  • Site 4: 286 samples
  • Site 5: 86 samples
  • Total S. aureus Test Set: 1183 samples
    (The sample sizes for MRSA and S. aureus appear to be derived from the same set of positive blood cultures.)

Data Provenance: The document states that the "Clinical trials were performed at five sites." While specific countries of origin for these sites are not explicitly mentioned, it is highly probable that the data were collected in the United States or Canada, given the submitter and contact information (BD Diagnostics, GeneOhm Sciences Canada Inc., with a US Agent in San Diego, CA). The study is prospective in nature, as it is a "clinical trial" evaluating the performance of a new diagnostic assay.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The ground truth was established by "reference methods" in clinical laboratories. These reference methods are listed as:

• Remel Staphaurex Latex Agglutination Test (for S. aureus)
• BBL (BD) Oxacillin Screen Agar (for MRSA)
• BD Phoenix Automated ID/AST System (for both S. aureus and MRSA)
• Culture/PBP2' Latex (for MRSA at Site 5)

The document does not specify the number of individual experts (e.g., microbiologists, lab technologists) who interpreted these reference methods at each site, nor their specific qualifications (e.g., years of experience). However, it is implied that these interpretations were performed by qualified laboratory personnel following standard laboratory protocols for these established diagnostic tests.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for discrepancies between the test device and the reference methods. The tables present a direct comparison of the BD GeneOhm™ StaphSR results against the respective reference method results at each site. Any disagreements would have been considered false positives or false negatives against the established reference standard.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study evaluates the performance of a diagnostic assay (BD GeneOhm™ StaphSR) against established laboratory reference methods, not the performance of human readers with or without AI assistance. Therefore, there is no effect size reported for human reader improvement with AI vs. without AI assistance.

6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, this was a standalone study in the context of a diagnostic test kit. The BD GeneOhm™ StaphSR Assay is a PCR-based molecular diagnostic test. The "performance" tables directly compare the output of the "BD GeneOhm™ StaphSR" assay (which includes the entire PCR and detection process interpreted by the SmartCycler software) against the reference culture/ID-AST systems. While human technicians perform the sample preparation and run the assay, the "result" generated by the device itself is interpreted by the SmartCycler software providing a final result at the end of the cycling program. This means the reported performance is the "algorithm only" or "device only" performance in its intended use.

7. The Type of Ground Truth Used

The ground truth used was established by standard microbiological culture and identification/antimicrobial susceptibility testing (ID/AST) methods, which are considered the gold standard for identifying bacterial species and their resistance patterns in clinical microbiology. Specifically, these included:

• Culture/ID-AST System 1, 2, 3
• Culture/Oxacillin Screen Agar
• Culture/PBP2' Latex

These are laboratory reference standards, often supported by expert interpretation of growth characteristics and biochemical or molecular profiles.

8. The Sample Size for the Training Set

The document does not provide information on the sample size for the training set. This is common for diagnostic assays of this type, where the "training" (development and optimization) often involves laboratory strains and characterized clinical isolates during the assay design phase, rather than a distinct, formally reported "training set" of patient samples in the same manner as machine learning models might have. The clinical trials described here represent the validation or test set.

9. How the Ground Truth for the Training Set Was Established

As no specific training set is detailed, the method for establishing its ground truth is also not provided. However, during the development of such assays, ground truth for optimization and development samples would typically be established using well-characterized clinical isolates and reference strains confirmed by extensive phenotypic and genotypic methods, including sequencing, to ensure accurate target and non-target differentiation.

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