K Number
K071026
Date Cleared
2007-12-20

(253 days)

Product Code
Regulation Number
866.1640
Reference & Predicate Devices
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

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.

Device Description

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.

AI/ML Overview

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.

Metric (Implicit Acceptance Criteria based on Predicate Device Performance)BD GeneOhm™ StaphSR Assay Performance (Across 5 Sites)
MRSA Detection:
Positive Agreement (Sensitivity)100% (Range: 100% across all sites)
Negative Agreement (Specificity)98.2% - 100% (Lowest: 98.2% at Site 2, Highest: 100% at Sites 3 & 5)
Overall Agreement98.5% - 100% (Lowest: 98.5% at Site 2, Highest: 100% at Sites 3 & 5)
S. aureus Detection:
Positive Agreement (Sensitivity)98.8% - 100% (Lowest: 98.8% at Site 4, Highest: 100% at Sites 1, 2, 3, 5)
Negative Agreement (Specificity)96.5% - 100% (Lowest: 96.5% at Site 4, Highest: 100% at Sites 1, 3, 5)
Overall Agreement97.2% - 100% (Lowest: 97.2% at Site 4, Highest: 100% at Sites 1, 3, 5)
Unresolved ResultsLow (Range: 0.0% - 0.3% initially; 0.0% - 0.0% on repeat)
Invalid AssaysLow (Range: 1.8% - 8.9% initially; 0.0% - 0.0% on repeat)

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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510(k) Summary: K071026

December 18, 2007

BD Diagnostics, BD GeneOhm™ StaphSR Assay Positive Blood Culture Indication

Submitted by:BD Diagnostics (GeneOhm Sciences Canada Inc.)2050, boul. René-Lévesque O, 4e étageSainte-Foy, Québec G1V 2K8 CANADA
Contact (US Agent):Raymond BouléSr. Director, RA/QM/RCBD Diagnostics - GeneOhm6146 Nancy Ridge DriveSan Diego, CA 92121 USA
DEC 2 0 2007
Name of Device:
Trade Name:BD GeneOhm™ StaphSR Assay
Common Name:Staphylococcus aureus and Methicillin-resistantStaphylococcus aureus detection assay
Classification Name:System, Test, Genotypic Detection, resistant and non-resistant markers, Staphylococcus colonies
Predicate Device:Performance:Remel Staphaurex Latex Agglutination Test (K851949)BBL (BD) Oxacillin Screen Agar (K863821)BD Phoenix Automated ID/AST System (K020322,K023301)
Technology:GeneOhm Sciences Canada BD GeneOhm™ MRSA Assa(K042357)

Device Description:

Intended Use:

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.

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Test Description:

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 singlestranded 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.

Substantial Equivalence:

The BD Diagnostics BD GeneOhm™ StaphSR Assay is substantially equivalent in technology to the currently marketed GeneOhm Sciences Canada BD GeneOhm™ MRSA Assay (K042357). The BD GeneOhm™ StaphSR Assay contains additional primers and molecular beacon probes to detect Staphylococcus aureus.

The GeneOhm BD GeneOhm™ StaphSR Assay is substantially equivalent in performance to the Remel Staphaurex Latex Agglutination Test (K851949) for detection of Staphylococcus aureus; the culture medium BBL (BD) Oxacillin Screen Agar (K863821) for detection of methicillin-resistant Staphylococcus aureus; and the BD Phoenix Automated ID/AST System (K020322, K023301) for detection of both Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. These methods were used as the reference methods in the clinical trials.

Clinical trials were performed at five sites to evaluate the performance of the BD GeneOhm™ StaphSR Assay. The results are summarized in Tables 1-5:

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Table 1. Results obtained with BD GeneOhm™ StaphSR for MRSA and S. aureus in comparison to the reference methods

S. aureus

Site 1
Culture/ID-AST System 1Culture/ID-AST System 1
BDGeneOhm™StaphSR++-BDGeneOhm™StaphSR++-
6156699099
03803800347347
6138544699347446
Site 2
Culture/ID-AST System 2Culture/ID-AST System 2
BDGeneOhm™StaphSR++-BDGeneOhm™StaphSR++-
2422640141
010710709292
241091334093133
Site 3
Culture/Oxacillin Screen AgarCulture/Oxacillin Screen Agar
BDGeneOhm™StaphSR++-BDGeneOhm™StaphSR++-
2102183083
02112110149149
2121123283149232
Site 4
Culture/ID-AST System 3Culture/ID-AST System 3
BDGeneOhm™StaphSR++-BDGeneOhm™StaphSR++-
4845284791
0234234-1194195
4823828685201286
Site 5
Culture/PBP2' LatexCulture/PBP2' Latex
BDGeneOhm™StaphSR++-BDGeneOhm™StaphSR++-
202808
08484-07878
2848687886

MRSA

Performance obtained with BD GeneOhm™ StaphSR for MRSA (by investigational site) in comparison to the Table 2. reference method.

SiteMRSAprevalenceMRSA Positive% Agreement(95% Cl) 1MRSA Negative% Agreement(95% CI) 1Overall% Agreement
Site 113.7% (61/446)100%(61/61) (94.1%-100%)98.7% (380/385) (97.0% - 99.6%)98.9%
Site 218.0% (24/133)100%(24/24) (85.8%-100%)98.2% (107/109) (93.5% - 99.8%)98.5%
Site 39.1% (21/232)100%(21/21) (83.9%-100%)100.0% (211/211) (98.3% - 100.0%)100%
Site 416.8% (48/286)100% (48/48)(92.6%-100%)98.3% (234/238) (95.8% - 99.5%)98.6%
Site 52.3% (2/86)100%(2/2) (15.8%-100%)100.0% (84/84) (95.7% - 100.0%)100%

1 Binomial 95% exact confidence intervals.

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Table 3. Performance obtained with BD GeneOhm™ StaphSR for S. aureus (by investigational site) in comparison to the reference method.

InvestigationalsiteS. aureusprevalenceS. aureus Positive% Agreement(95% CI) ,S. aureus Negative% Agreement(95% CI) 1Overall% Agreement
Site 122.2% (99/446)100.0% (99/99) (96.3%-100%)100% (347/347)(98.9%-100%)100%
Site 230.1% (40/133)100% (40/40)(91.2%-100%)98.9% (92/93) (94.2%-100%)99.2%
Site 335.8% (83/232)100% (83/83)( 95.7%-100%)100% (149/149) (97.6%-100%)100%
Site 429.7% (85/286)98.8% (84/85) (93.6% - 100.0%)96.5% (194/201) (93.0% - 98.6%)97.2%
Site 59.3% (8/86)100% (8/8) (63.1% - 100.0%)100% (78/78) (95.4%-100%)100%

1 Binomial 95% exact confidence intervals.

Table 4. Unresolved results

Investigationalsite% Initial Unresolved with 95%exact confidence intervals% Repeat Unresolved with 95%exact confidence intervals
Site 10.0% (0/446)(0.0% - 0.8%)0.0% (0/446)(0.0% - 0.8%)
Site 20.0% (0/133)(0.0% - 2.7%)0.0% (0/133)(0.0% - 2.7%)
Site 30.0% (0/232)(0.0% - 1.6%)0.0% (0/232)(0.0% - 1.6%)
Site 40.3% (1/286)(0.0% - 1.9%)0.0% (1/286)(0.0% - 1.3%)
Site 50.0% (0/86)(0.0% - 4.2%)0.0% (0/86)(0.0% - 4.2%)

Table 5. Invalid assays

Investigationalsite% Initial invalid runs with 95%exact confidence intervals% Invalid repeat runs with 95%exact confidence intervals
Site 11.8% (2/113) (0.2% - 6.2%)0.0% (0/113) (0.0% - 3.2%)
Site 28.9% (5/56) (3.0% - 19.6%)0.0% (0/56) (0.0% - 6.4%)
Site 32.9% (2/69) (0.4% - 10.1%)0.0% (0/69) (0.0% - 5.2%)
Site 42.4% (2/84) (0.3% - 8.3%)0.0% (0/84) (0.0% - 4.3%)
Site 57.7% (5/65) (2.5% - 17.0%)0.0% (0/65) (0.0% - 5.5%)

·

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle-like symbol with three curved lines representing its wings or feathers. The symbol is positioned to the right of the text, which is arranged in a circular pattern around the symbol. The text reads "DEPARTMENT OF HEALTH & HUMAN SERVICES USA".

DEC 2 0 2007

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Raymond Boulé Senior Director, Regulatory Affairs BD Diagnostics (GeneOhm Sciences Canada, Inc.) 6146 Nancy Ridge Drive San Diego, CA 92121

K071026 Re: Trade/Device Name: BD GeneOhm™ StaphSR Assay Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: Class II Product Code: NQX Dated: November 23, 2007 Received: November 26, 2007

Dear Mr. Boulé:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240-276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ' (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Sally attaym

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

K071026 510(k) Number (if known):

BD GeneOhm™ StaphSR Assay Device Name:

Indications For Use:

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.

OR Prescription Use XXX

(Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices Evaluation and Safety (OIVD)

Freddie Poole
Division Sign-Off

vision Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K071026

§ 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).