(422 days)
The BD GeneOhm™ VanR Assay is a qualitative in vitro test for the rapid detection of vancomycin-resistance (vanA and vanB) genes directly from perianal or rectal swabs. The BD GeneOhm™ VanR Assay detects the presence of the vanA and vanB genes that can be associated with vancomycin-resistant enterococci (VRE). The assay is performed on an automated real-time PCR instrument with perianal or rectal swabs from individuals at risk for VRE colonization. The BD GeneOhm™ VanR Assay can be used as an aid to identify, prevent and control vancomycin-resistant colonization in healthcare settings. The BD GeneOhm™ VanR Assay is not intended to diagnose VRE infections nor to guide or monitor treatment for VRE infections. Concomitant cultures are necessary to recover organisms for epidemiological typing, susceptibility testing and for further confirmatory identification.
Following specimen lysis, the vanA and vanB genetic targets, if present, are amplified. Amplification of the Internal Control (IC), a DNA fragment of 294-bp including a 254-bp sequence not found in VRE, will also take 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 the vanA amplicon, the molecular beacon probe contains the fluorophore FAM at the 5' end and the nonfluorescent quencher moiety DABCYL at the opposite 3' end of the oligonucleotide. For the detection of the vanB amplicon, the molecular beacon probe contains the fluorophore Texas Red 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 molecular beacon probe, interprets all data, and provides a final result at the end of the cycling program.
Here's a summary of the acceptance criteria and study details for the BD GeneOhm™ VanR Assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific performance thresholds (e.g., "Sensitivity must be >X%"). Instead, the study aims to demonstrate substantial equivalence to the predicate device. The performance is reported in terms of observed sensitivity and specificity (or Positive Percent Agreement and Negative Percent Agreement). The tables below summarize the overall clinical performance across all sites.
| Metric (for VanR detection) | Acceptance Criteria (Implicit: Demonstrate substantial equivalence) | Reported Device Performance (Overall) - Perianal Specimens | Reported Device Performance (Overall) - Rectal Specimens |
|---|---|---|---|
| Sensitivity (using Direct/Enriched Culture) | Sufficiently High (to be equiv. to predicate) | 92.9% (87.7% - 96.4% CI) | 93.1% (87.4% - 96.8% CI) |
| Specificity (using Direct/Enriched Culture) | Sufficiently High (to be equiv. to predicate) | 86.0% (83.8% - 87.9% CI) | 82.2% (79.2% - 85.0% CI) |
| Positive Percent Agreement (using Direct Culture) | Sufficiently High (to be equiv. to predicate) | 95.0% (89.3%-98.1% CI) | 95.5% (89.9%-98.5% CI) |
| Negative Percent Agreement (using Direct Culture) | Sufficiently High (to be equiv. to predicate) | 83.9% (81.7%-86.0% CI) | 81.0% (77.9%-83.8% CI) |
| Unresolved Rate (final) | Low | 0.3% (0.1% - 0.6% CI) | 0.3% (0.1% - 0.6% CI) (Overall study rate) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Test Set):
- Direct/Enriched Culture Comparison: 2156 specimens (1316 perianal and 834 rectal specimens). 2150 reportable results.
- Direct Culture Comparison: 2152 specimens (1314 perianal and 832 rectal specimens). 2146 reportable results.
- Data Provenance: The study was a "multisite prospective investigational study" conducted across "Five (5) medical centers." The country of origin is not explicitly stated, but the submission is to the US FDA, implying US-based or internationally accepted clinical trial standards. The study design is prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts involved in establishing the ground truth. The reference method involved a multi-step microbiological process. While it implicitly requires expert laboratory personnel to perform and interpret these complex tests, no specific "expert" panel for ground truth adjudication is mentioned.
4. Adjudication Method for the Test Set
No explicit adjudication method (like 2+1 or 3+1) is described for the test set. The ground truth (Reference Method) was established through a defined laboratory protocol involving direct culture, enriched culture, phenotypic identification of Enterococcus colonies, vancomycin resistance testing (MIC method), and genotypic characterization of vanA or vanB genes using alternative PCR. This is a sequential, algorithm-driven process rather than an independent expert adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This device is a molecular diagnostic assay, not an imaging-based diagnostic tool that typically involves human reader interpretation. The comparison is between the automated PCR assay and a laboratory reference method.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done
Yes, the performance characteristics presented are for the standalone algorithm (BD GeneOhm™ VanR Assay). The device is a "qualitative in vitro test for the rapid detection of vancomycin-resistance (vanA and vanB) genes directly from perianal or rectal swabs" performed on "an automated real-time PCR instrument." The reported performance metrics (sensitivity, specificity etc.) are the direct output of this automated system compared to the reference method.
7. The Type of Ground Truth Used
The ground truth used was a "Reference Method" consisting of:
- Direct Culture complemented by Enriched Culture.
- Inoculation onto Bile Esculin Azide agar supplemented with 6 µg/mL vancomycin (BEAV).
- Phenotypic identification of presumptive Enterococcus colonies (PYR test, commercial tests for species identification).
- Vancomycin resistance determined using an MIC method.
- Genotypic characterization of vanA and vanB genes using alternative PCR for confirmed vancomycin-resistant enterococcal isolates.
A "vanA- and/or vanB-containing VRE positive specimen" was defined as a specimen with vancomycin-resistant enterococci from culture with vanA and/or vanB genes identified by alternative PCR. A negative specimen was defined as negative by both direct and enriched culture methods.
8. The Sample Size for the Training Set
The document provided (510(k) summary) does not specify a separate "training set" for the BD GeneOhm™ VanR Assay. Clinical performance studies typically involve a "test set" to evaluate the device against a reference method. For molecular assays, assay development involves extensive internal validation and optimization with various samples, but these are generally not described as a "training set" in the same way machine learning models would have one. The focus here is on the performance of the developed assay on a clinical validation cohort.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" is described for this type of device in the provided document, the method for establishing its ground truth is not detailed. However, the ground truth for the clinical validation (test set), as described in point 7, involved a comprehensive microbiological and molecular reference method. This rigorous reference method would implicitly guide the development and optimization of the assay during its pre-clinical phase.
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OCT 2 0 2011
510(k) Summary
October 17, 2011
K102416 BD GeneOhm™ VanR Assay
| Submitted by: | BD Diagnostics (GeneOhm Sciences, Inc.)7 Loveton Circle, Mail Code 614Sparks, MD 21152, USA |
|---|---|
| Contact: | Raymond J. BouléDirector, Regulatory AffairsMolecular Diagnostics - MAX Platform |
| Name of Device: | |
| Trade Name: | BD GeneOhm™ VanR Assay |
| Common Name: | Vancomycin-resistant Enterococci detection assay |
| Classification Name: | System, Nucleic Acid Amplification Test, DNA, VancomycinResistant Bacteria, Direct Specimen |
| Predicate Device: | Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV)(K972359) |
Device Description:
Intended Use:
The BD GeneOhm™ VanR Assay is a qualitative in vitro test for the rapid detection of vancomycin-resistance (vanA and vanB) genes directly from perianal or rectal swabs. The BD GeneOhm™ VanR Assay detects the presence of the vanA and vanB genes that can be associated with vancomycin-resistant enterococci (VRE). The assay is performed on an automated real-time PCR instrument with perianal or rectal swabs from individuals at risk for VRE colonization. The BD GeneOhm™ VanR Assay can be used as an aid to identify, prevent and control vancomycin-resistant colonization in healthcare settings. The BD GeneOhm™ VanR Assay is not intended to diagnose VRE infections nor to guide or monitor treatment for VRE infections. Concomitant cultures are necessary to recover organisms for epidemiological typing, susceptibility testing and for further confirmatory identification.
Test Description:
Following specimen lysis, the vanA and vanB genetic targets, if present, are amplified. Amplification of the Internal Control (IC), a DNA fragment of 294-bp including a 254-bp sequence not found in VRE, will also take 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
{1}------------------------------------------------
quenched. In the presence of target, the hairpin structure opens upon beacon/target hybridization, resulting in emission of fluorescence. For the detection of the vanA amplicon, the molecular beacon probe contains the fluorophore FAM at the 5' end and the nonfluorescent quencher moiety DABCYL at the opposite 3' end of the oligonucleotide. For the detection of the vanB amplicon, the molecular beacon probe contains the fluorophore Texas Red 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 molecular beacon probe, interprets all data, and provides a final result at the end of the cycling program.
Substantial Equivalence:
The BD GeneOhm™ VanR Assay was originally cleared under premarket notification K061686 as the GeneOhm Sciences Canada, Inc. IDI-VanR™ Assay, for use with the rectal swab specimen collection method. This 510(k) notification was submitted for use with an additional specimen collection method, specifically, the perianal swab specimen collection method.
Additional clinical performance studies were performed to support the claims for either perianal or rectal specimen collection methods. The BD GeneOhm™ VanR Assay has been found to be substantially equivalent to the Remel Bile Esculin Azide agar with 6 ug/mL vancomvcin (BEAV) (K972359) with phenotypic identification of Enterococcus colonies and confirmation of vancomycin resistance for the detection of vancomycin resistant Enterococcus, followed by genotypic characterization of the vanA or the vanB gene with alternative PCR.
Clinical Performance:
Performance characteristics of the BD GeneOhm™ VanR Assay were determined in a multisite prospective investigational study. Five (5) medical centers participated in the study. To be enrolled in the study, specimens had to be from individuals for whom cultures were indicated and/or ordered, according to institutional policies.
The Reference Method consisted of direct culture complemented by enriched culture. Enriched culture analysis was completed for all specimens that were negative for VRE by direct culture. Direct culture was performed by inoculating specimens onto a primary isolation media containing Bile Esculin Azide agar supplemented with 6 µg/mL vancomycin (BEAV). Enriched culture was performed by incculating 300 uL of sample buffer containing the specimen into BEA broth or BEAV broth (BEA broth supplemented with 6 ug/mL vancomycin). Confirmed enterococcal colonies were tested for vancomycin resistance. Genotypic characterization of confirmed vancomycin-resistant enterococcal isolates was performed using alternative PCR.
For the Reference Method, plates were directly inoculated with swab specimens followed by incubation at 35°C for 24 to 48 hours. Presumptive colonies of Enterococcus were subcultured to 5% sheep blood agar plates and incubated for 18-24 hours at 35°C. Colonies presumptive for the Enterococcus genus underwent the pyrrolidonyl arylamidase (PYR) test.
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If the PYR test was positive, enterococcal species identification was performed using appropriate commercial tests. Vancomycin resistance was determined for confirmed enterococci using an MIC method. Confirmed VRE isolates underwent alternative PCR testing for genotypic characterization of vanA and vanB genes. An enrichment step in BEA broth or BEAV broth (BEA broth supplemented with vancomycin 6 □g/mL) was performed in cases where a negative result for vancomycin resistance was obtained with enterococci isolated from the BEAV plate or when no enterococci were isolated. For this purpose, the broth was incculated with 300 µL of sample buffer containing the specimen, and incubated 24 to 48 hours at 35°C. Any broth culture that exhibited black growth was subcultured to a BEAV plate and incubated 24 to 48 hours at 35°C. Presumptive colonies of Enterococcus were subcultured to 5% sheep blood agar plates and incubated for 18-24 hours at 35°C. Confirmation of presumptive colonies and determination of vancomycin resistance was performed as described above. Confirmed VRE isolates underwent alternative PCR testing for genotypic characterization of vanA and vanB genes.
A vanA- and/or vanB-containing VRE positive specimen was defined as a specimen with vancomycin-resistant enterococci from culture with vanA and/or vanB genes identified by alternative PCR: a VanR-positive specimen was defined as a VRE having vanA, vanB or both. A negative specimen was defined as a specimen negative for vancomycin-resistant enterococci by both direct and enriched culture methods.
A total of 2156 specimens were tested using Direct/Enriched culture with alternative PCR and the BD GeneOhm VanR™ Assay, producing 2150 reportable results. Tables 1A and 1B show the final results (1316 perianal and 834 rectal specimens) of the BD GeneOhm VanR™ Assay in comparison to Direct/Enriched culture with alternative PCR. Two hundred and twenty-two (222) specimens (123 perianal and 99 rectal) were culture negative but positive for vanB only by the BD GeneOhm VanR™ PCR and may represent detection of the vanB gene in non-enterococcal organisms. Further investigation for non-enterococcal organisms that might contain the vanB gene was not performed.
In comparison to Direct/Enriched culture with alternative PCR, the BD GeneOhm™ VanR Assay identified 81.3% to 100% of the VanR-positive specimens and 72.7% to 93.1% of the neqative specimens (Table 3A). The BD GeneOhm™ VanR Assay identified 92.9% and 93.1% of the perianal and rectal positive specimens, respectively, and identified 86.0% and 82.2% of the perianal and rectal negative specimens, respectively (Tables 2A and 2B).
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Tables 1A-B. Results Obtained with the BD GeneOhm™ VanR Assay in Comparison to Direct/Enriched Culture with Alternative PCR
| Table 1A. Perianal Specimens | Direct/Enriched Culture + Alternative PCR | |||||
|---|---|---|---|---|---|---|
| VRE withvanAGenotype | VRE withvanBGenotype | VRE withvanA andvanBGenotype | Negative | Total | ||
| BD GeneOhm™VanRResults | vanA | 106 | 0 | 0 | 35 | 141 |
| vanA and vanB | 28 | 0 | 0 | 5 | 33 | |
| vanB | 7 | 3 | 0 | 123 | 133 | |
| Negative | 11 | 0 | 0 | 998 | 1009 | |
| Total | 152 | 3 | 0 | 1161 | 1316 |
| Table 1B. Rectal Specimens | Direct/Enriched Culture + Alternative PCR | |||||
|---|---|---|---|---|---|---|
| VRE withvanAGenotype | VRE withvanBGenotype | VRE withvanA andvanBGenotype | Negative | Total | ||
| BD GeneOhm™VanRResults | vanA | 75 | 0 | 0 | 20 | 95 |
| vanA and vanB | 32 | 2 | 1 | 6 | 41 | |
| vanB | 8 | 4 | 0 | 99 | 111 | |
| Negative | 9 | 0 | 0 | 578 | 587 | |
| Total | 124 | 6 | 1 | 703 | 834 |
Tables 2A-B.Clinical Performance Obtained with the BD GeneOhm™ VanR Assay by Specimen Type in Comparison to Direct/Enriched Culture with Alternative PCR
Table 2A. Perianal Specimens
| Sensitivity(95% CI') | Specificity(95% CI') | VRE Prevalence | PPV(95% CI') | NPV(95% CI') | |
|---|---|---|---|---|---|
| vanA | 88.2%(134/152)(81.9% - 92.8%) | 96.6%(1124/1164)(95.3% - 97.5%) | 11.1%(152/1372) | 77.0%(134/174)(70.0% - 83.0%) | 98.4%(1124/1142)(97.5% - 99.1%) |
| vanB | 100.0%(3/3)(29.2% - 100.0%) | 87.6%(1150/1313)(85.7% - 89.3%) | 0.2%(3/1372) | 1.8%(3/166)(0.4% - 5.2%) | 100.0%(1150/1150)(99.7% - 100.0%) |
| VanR | 92.9%(144/155)(87.7% - 96.4%) | 86.0%(998/1161)(83.8% - 87.9%) | 11.3%(155/1372) | 46.9%(144/307)(41.2% - 52.7%) | 98.9%(998/1009)(98.1% - 99.5%) |
' Binomial 95% exact confidence intervals.
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Table 2B. Rectal Specimens
| Sensitivity(95% CI¹) | Specificity(95% CI¹) | VRE Prevalence | PPV(95% CI¹) | NPV(95% CI¹) | |
|---|---|---|---|---|---|
| vanA | 86.4%(108/125)(79.1% - 91.9%) | 96.1%(681/709)(94.3% - 97.4%) | 15.4%(133/863) | 79.4%(108/136)(71.6% - 85.9%) | 97.6%(681/698)(96.1% - 98.6%) |
| vanB | 100.0%(7/7)(59.0% - 100.0%) | 82.5%(682/827)(79.7% - 85.0%) | 1.0%(9/863) | 4.6%(7/152)(1.9% - 9.3%) | 100.0%(682/682)(99.5% - 100.0%) |
| VanR | 93.1%(122/131)(87.4% - 96.8%) | 82.2%(578/703)(79.2% - 85.0%) | 16.3%(141/863) | 49.4%(122/247)(43.0% - 55.8%) | 98.5%(578/587)(97.1% - 99.3%) |
Binomial 95% exact confidence intervals.
Tables 3A-C. Clinical Performance Obtained with the BD GeneOhm™ VanR Assay by site in Comparison to Direct/Enriched Culture with Alternative PCR
Table 3A. VanR
| Investigational Site | Collection Method | VRE Prevalence | Sensitivity (95% CI1) | Specificity (95% CI1) |
|---|---|---|---|---|
| Site 1 | Perianal | 8.6% (16/185) | 81.3% (13/16) (54.4% - 96.0%) | 93.1% (134/144) (87.6% - 96.6%) |
| Rectal | 17.0% (19/112) | 100.0% (17/17) (80.5% - 100.0%) | 75.3% (67/89) (65.0% - 83.8%) | |
| Site 2 | Perianal | 15.6% (60/385) | 100.0% (54/54) (93.4% - 100.0%) | 81.0% (217/268) (75.8% - 85.5%) |
| Site 3 | Rectal | 23.4% (79/338) | 94.3% (66/70) (86.0% - 98.4%) | 72.7% (168/231) (66.5% - 78.4%) |
| Site 4 | Perianal | 9.5% (75/789) | 90.1% (73/81) (81.5% - 95.6%) | 86.5% (640/740) (83.8% - 88.9%) |
| Rectal | 10.1% (8/79) | 88.9% (8/9) (51.8% - 99.7%) | 83.3% (60/72) (72.7% - 91.1%) | |
| Site 5 | Perianal | 30.8% (4/13) | 100.0% (4/4) (39.8% - 100.0%) | 77.8% (7/9) (40.0% - 97.2%) |
| Rectal | 10.5% (35/334) | 88.6% (31/35) (73.3% - 96.8%) | 91.0% (283/311) (87.3% - 93.9%) |
Binomial 95% exact confidence intervals.
Table 3B. vanA
| Investigational Site | Collection Method | VRE Prevalence | Sensitivity (95% CI¹) | Specificity (95% CI¹) |
|---|---|---|---|---|
| Site 1 | Perianal | 8.6% (16/185) | 81.3% (13/16) (54.4% - 96.0%) | 98.6% (142/144) (95.1% - 99.8%) |
| Rectal | 17.0% (19/112) | 94.1% (16/17) (71.3% - 99.9%) | 97.8% (87/89) (92.1% - 99.7%) | |
| Site 2 | Perianal | 15.3% (59/385) | 96.2% (51/53) (87.0% - 99.5%) | 91.4% (246/269) (87.4% - 94.5%) |
| Site 3 | Rectal | 21.0% (71/338) | 84.4% (54/64) (73.1% - 92.2%) | 93.2% (221/237) (89.3% - 96.1%) |
| Site 4 | Perianal | 9.3% (73/789) | 84.8% (67/79) (75.0% - 91.9%) | 98.1% (728/742) (96.9% - 99.0%) |
| Rectal | 10.1% (8/79) | 88.9% (8/9) (51.8% - 99.7%) | 100.0% (72/72) (95.0% - 100.0%) | |
| Site 5 | Perianal | 30.8% (4/13) | 75.0% (3/4) (19.4% - 99.4%) | 88.9% (8/9) (51.8% - 99.7%) |
| Rectal | 10.5% (35/334) | 85.7% (30/35) (69.7% - 95.2%) | 96.8% (301/311) (94.2% - 98.4%) |
Binomial 95% exact confidence intervals.
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Table 3C. vanB
| Investigational Site | Collection Method | VRE Prevalence | Sensitivity (95% CI¹) | Specificity (95% CI¹) |
|---|---|---|---|---|
| Site 1 | Perianal | 0.0% (0/185) | No data for sensitivity rate calculation | 93.8% (150/160) (88.8% - 97.0%) |
| Rectal | 0.0% (0/112) | No data for sensitivity rate calculation | 75.5% (80/106) (66.2% - 83.3%) | |
| Site 2 | Perianal | 0.3% (1/385) | 100.0% (1/1) (2.5% - 100.0%) | 87.5% (281/321) (83.4% - 90.9%) |
| Site 3 | Rectal | 2.7% (9/338) | 100.0% (7/7) (59.0% - 100.0%) | 73.5% (216/294) (68.0% - 78.4%) |
| Site 4 | Perianal | 0.3% (2/789) | 100.0% (2/2) (15.8% - 100.0%) | 86.7% (710/819) (84.2% - 88.9%) |
| Rectal | 0.0% (0/79) | No data for sensitivity rate calculation | 81.5% (66/81) (71.3% - 89.2%) | |
| Site 5 | Perianal | 0.0% (0/13) | No data for sensitivity rate calculation | 69.2% (9/13) (38.6% - 90.9%) |
| Rectal | 0.0% (0/334) | No data for sensitivity rate calculation | 92.5% (320/346) (89.2% - 95.0%) |
Binomial 95% exact confidence intervals.
A total of 2152 specimens were tested using Direct Culture with alternative PCR and the BD GeneOhm VanR™ Assay, producing 2146 reportable results. Tables 4A and 4B show the final results (1314 perianal and 832 rectal specimens) of the BD GeneOhm VanR™ Assay in comparison to Direct Culture with alternative PCR. Two hundred and thirty-one (231) specimens (129 perianal and 102 rectal) were culture negative but positive for vanB only by the BD GeneOhm VanR™ PCR and may represent detection of the vanB gene in nonenterococcal organisms. Further investigation for non-enterococcal organisms that might contain the vanB gene was not performed.
In comparison to Direct Culture with alternative PCR, the BD GeneOhm™ VanR Assay identified 86.7% to 100% of the VanR-positive specimens and 71.0% to 93.1% of the negative specimens (Table 6A). The BD GeneOhm™ VanR Assay identified 95.0% and 95.5% of the perianal and rectal positive specimens, respectively, and identified 83.9% and 81.0% of the perianal and rectal negative specimens, respectively (Tables 5A and 5B).
Tables 4A-B. Results Obtained with the BD GeneOhm™ VanR Assay in Comparison to Direct Culture with Alternative PCR
| Table 4A. Perianal Specimens | Direct Culture + Alternative PCR | |||||
|---|---|---|---|---|---|---|
| VRE withvanAGenotype | VRE withvanBGenotype | VRE withvanA andvanBGenotype | Negative | Total | ||
| BD GeneOhm™VanRResults | vanA | 82 | 0 | 0 | 57 | 139 |
| vanA and vanB | 27 | 0 | 0 | 6 | 33 | |
| vanB | 3 | 1 | 0 | 129 | 133 | |
| Negative | 6 | 0 | 0 | 1003 | 1009 | |
| Total | 118 | 1 | 0 | 1195 | 1314 |
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| Table 4B. Rectal Specimens | Direct Culture + Alternative PCR | |||||
|---|---|---|---|---|---|---|
| VRE withvanAGenotype | VRE withvanBGenotype | VRE withvanA andvanBGenotype | Negative | Total | ||
| BD GeneOhm™VanRResults | vanA | 65 | 0 | 0 | 28 | 93 |
| vanA and vanB | 31 | 2 | 1 | 7 | 41 | |
| vanB | 4 | 4 | 0 | 102 | 110 | |
| Negative | 5 | 0 | 0 | 583 | 588 | |
| Total | 105 | 6 | 1 | 720 | 832 |
Tables 5A-B. Clinical Performance Obtained with the BD GeneOhm™ VanR Assay by Specimen Type in Comparison to Direct Culture with Alternative PCR
Table 5A. Perianal Specimens
| Positive Percent Agreement(95% CI1) | Negative Percent Agreement(95% CI1) | |
|---|---|---|
| vanA | 92.4%(109/118)(86.0%-96.5%) | 94.7%(1133/1196)(93.3%-95.9%) |
| vanB | 100.0%(1/1)(2.5%-100.0%) | 87.4%(1148/1313)(85.5%-89.2%) |
| VanR | 95.0%(113/119)(89.3%-98.1%) | 83.9%(1003/1195)(81.7%-86.0%) |
1 Binomial 95% exact confidence intervals.
Table 5B. Rectal Specimens
| Positive Percent Agreement(95% CI1) | Negative Percent Agreement(95% CI1) | |
|---|---|---|
| vanA | 91.5%(97/106)(84.5%-96.0%) | 94.9%(689/726)(93.0%-96.4%) |
| vanB | 100.0%(7/7)(59.0%-100.0%) | 82.5%(681/825)(79.8%-85.1%) |
| VanR | 95.5%(107/112)(89.9%-98.5%) | 81.0%(583/720)(77.9%-83.8%) |
1 Binomial 95% exact confidence intervals.
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Tables 6A-C. Clinical Performance Obtained with the BD GeneOhm™ VanR Assay by Site in Comparison to Direct Culture with Alternative PCR
Table 6A. VanR
| Investigational Site | Collection Method | Positive Percent Agreement(95% CI1) | Negative Percent Agreement(95% CI1) |
|---|---|---|---|
| Site 1 | Perianal | 86.7% (13/15) (59.5% - 98.3%) | 93.1% (135/145) (87.7% - 96.6%) |
| Rectal | 100.0% (16/16) (79.4% - 100.0%) | 74.4% (67/90) (64.2% - 83.1%) | |
| Site 2 | Perianal | 100.0% (35/35) (90.0% - 100.0%) | 75.6% (217/287) (70.2% - 80.5%) |
| Site 3 | Rectal | 95.2% (59/62) (86.5% - 99.0%) | 71.0% (169/238) (64.8% - 76.7%) |
| Site 4 | Perianal | 93.8% (61/65) (85.0% - 98.3%) | 85.4% (644/754) (82.7% - 87.9%) |
| Rectal | 100.0% (6/6) (51.1% - 100.0%) | 81.3% (61/75) (70.7% - 89.4%) | |
| Site 5 | Perianal | 100.0% (4/4) (39.8% - 100.0%) | 77.8% (7/9) (40.0% - 97.2%) |
| Rectal | 92.9% (26/28) (76.5% - 99.1%) | 90.2% (286/317) (86.4% - 93.3%) |
Binomial 95% exact confidence intervals.
Table 6B. vanA
| Investigational Site | Collection Method | Positive Percent Agreement(95% CI1) | Negative Percent Agreement(95% CI1) |
|---|---|---|---|
| Site 1 | Perianal | 86.7% (13/15) (59.5%-98.3%) | 98.6% (143/145) (95.1%-99.8%) |
| Rectal | 100.0% (16/16) (79.4% - 100.0%) | 97.8% (88/90) (92.2% - 99.7%) | |
| Site 2 | Perianal | 97.1% (33/34) (84.7% - 99.9%) | 85.8% (247/288) (81.2%- 89.6%) |
| Site 3 | Rectal | 87.5% (49/56) (75.9% - 94.8%) | 91.4% (223/244) (87.1%- 94.6%) |
| Site 4 | Perianal | 92.3% (60/65) (83.0% - 97.5%) | 97.5% (735/754) (96.1% - 98.5%) |
| Rectal | 100.0% (6/6) (54.1% - 100.0%) | 97.3% (73/75) (90.7% - 99.7%) | |
| Site 5 | Perianal | 75.0% (3/4) (19.4% - 99.4%) | 88.9% (8/9) (51.8% - 99.7%) |
| Rectal | 92.9% (26/28) (76.5-99.1%) | 96.2% (305/317) (93.5%- 98.0%) |
Binomial 95% exact confidence intervals
Table 6C. vanB
| Investigational Site | Collection Method | Positive Percent Agreement(95% CI1) | Negative Percent Agreement(95% CI1) |
|---|---|---|---|
| Site 1 | Perianal | No data for sensitivity rate calculation | 93.8% (150/160) (88.8% - 97.0%) |
| Rectal | No data for sensitivity rate calculation | 75.5% (80/106) (66.2% - 83.3%) | |
| Site 2 | Perianal | 100.0% (1/1) (2.5% - 100.0%) | 87.5% (281/321) (83.4% - 90.9%) |
| Site 3 | Rectal | 100.0% (7/7) (59.0% - 100.0%) | 73.7% (216/293) (68.3% - 78.7%) |
| Site 4 | Perianal | No data for sensitivity rate calculation | 86.4% (708/819) (83.9% - 88.7%) |
| Rectal | No data for sensitivity rate calculation | 81.5% (66/81) (71.3% - 89.2%) | |
| Site 5 | Perianal | No data for sensitivity rate calculation | 69.2% (9/13) (38.6% - 90.9%) |
| Rectal | No data for sensitivity rate calculation | 92.5% (319/345) (89.2% - 95.0%) |
" Binomial 95% exact confidence intervals.
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Twenty-three (23) specimens gave an initial Unresolved result (i.e. failure of the internal control), giving a rate of 1.1%. Upon retest, 17 of these specimens gave a reportable result whereas only 6 specimens remained Unresolved, producing a final Unresolved rate of 0.3% (Table 7).
| Investigational Site | Initial unresolved rate (95% CI') | Unresolved rate after repeat (95% CI') |
|---|---|---|
| Site 1 | 0.0% (0/266) (0.0% - 1.4%) | 0.0% (0/266) (0.0% - 1.4%) |
| Site 2 | 1.9% (6/322) (0.7% - 4.0%) | 0.0% (0/322) (0.0% - 1.1%) |
| Site 3 | 1.7% (5/301) (0.5% - 3.8%) | 0.0% (0/301) (0.0% - 1.2%) |
| Site 4 | 1.1% (10/908) (0.5% - 2.0%) | 0.7% (6/908) (0.2% - 1.4%) |
| Site 5 | 0.6% (2/359) (0.1% - 2.0%) | 0.0% (0/359) (0.0% - 1.0%) |
| Overall study | 1.1% (23/2156) (0.7% - 1.6%) | 0.3% (6/2156) (0.1% - 0.6%) |
Table 7. Initial and Repeat Unresolved Rates of the BD GeneOhm™ VanR Assay
1 Binomial 95% exact confidence intervals.
{9}------------------------------------------------
DEPARTMENT OF HEALTH & HUMAN SERVICES
1
Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of three human profiles facing right, stacked on top of each other. The graphic is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
BD Diagnostics (GeneOhm Sciences, Inc.) c/o Mr. Raymond J. Boulé Director, Regulatory Affairs 7 Loveton Circle, Mail Code 614 Sparks, MD 21152
OCT 2 0 2011
Re: K102416
Trade/Device Name: BD GeneOhm™ VanR Assay Regulation Number: 21 CFR$866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: Class II Product Code: NIJ Dated: October 18, 2011 Received: October 18, 2011
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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
{10}------------------------------------------------
Page- 2 - Mr. Raymond Boulé
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 Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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 (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Vay, aHymir
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices Radiological Health
Enclosure
{11}------------------------------------------------
Indications for Use Statement
510(k) Number (if known): K102416
Device Name: BD GeneOhm™ VanR Assay
Indications For Use:
Intended Use
The BD GeneOhm™ VanR Assay is a qualitative in vitro test for the rapid detection of vancomvcinresistance (vanA and vanB) genes directly from perianal or rectal swabs. The BD GeneOhm™ VanR Assay detects the presence of the vanA and vanB genes that can be associated with vancomvcinresistant enterococci (VRE). The assay is performed on an automated real-time PCR instrument with perianal or rectal swabs from individuals at risk for VRE colonization. The BD GeneOhm™ VanR Assay can be used as an aid to identify, prevent and control vancomvcin-resistant colonization in healthcare settings. The BD GeneOhm™ VanR Assay is not intended to diagnose VRE infections nor to guide or monitor treatment for VRE infections. Concomitant cultures are necessary to recover organisms for epidemiological typing, susceptibility testing and for further confirmatory identification.
Prescription Use
Over-The-Counter Use
(Per 21 CFR 801.109)
(Optional Format 1-2-96)
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
OR
Concurrence of CDRH, Office of In Vitro Diagnostic Devices Evaluation and Safety (OIVD)
Freddie Lee Poole
Civision Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K102416
§ 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).