BD GENEOHM VANR ASSAY

K102416 · Bd Diagnostics Science · NIJ · Oct 20, 2011 · Microbiology

Device Facts

• Record ID: K102416
• Device Name: BD GENEOHM VANR ASSAY
• Applicant: Bd Diagnostics Science
• Product Code: NIJ · Microbiology
• Decision Date: Oct 20, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

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.

Device Story

The BD GeneOhm™ VanR Assay is a molecular diagnostic test for detecting vanA and vanB genes associated with VRE. Input consists of perianal or rectal swabs. The assay uses real-time PCR to amplify target genes and an internal control (IC). Molecular beacon probes (hairpin-forming oligonucleotides with fluorophore/quencher pairs) detect amplified DNA; fluorescence emission indicates target presence. The SmartCycler® instrument performs thermal cycling and monitors fluorescence. Software interprets data to provide qualitative results. Used in healthcare settings to identify VRE colonization for infection control. Results aid in screening; they do not diagnose active infection or guide therapy. Concomitant cultures are required for confirmation and susceptibility testing.

Clinical Evidence

Multisite prospective study (5 centers, 2156 specimens). Compared BD GeneOhm™ VanR Assay to reference method (direct/enriched culture + alternative PCR). Sensitivity for VanR ranged 81.3%–100% (perianal) and 88.6%–100% (rectal). Specificity ranged 69.2%–98.6% (perianal) and 73.5%–100% (rectal). Initial unresolved rate 1.1%, reduced to 0.3% after retest.

Technological Characteristics

Real-time PCR assay; uses molecular beacons (FAM, Texas Red, TET fluorophores). Automated SmartCycler® System with I-CORE™ modules. Reagents: Master Mix, Control DNA, Diluent. Software-based interpretation of fluorescence. Sterilization/materials not specified beyond standard lab reagents.

Indications for Use

Indicated for individuals at risk for VRE colonization; qualitative detection of vanA and vanB genes from perianal or rectal swabs to aid in identification, prevention, and control of VRE colonization in healthcare settings. Not for diagnosing VRE infections or monitoring treatment.

Regulatory Classification

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.

Predicate Devices

• Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV) (K972359)

Submission Summary (Full Text)

{0}------------------------------------------------

OCT 2 0 2011

## 510(k) Summary

October 17, 2011

# K102416 BD GeneOhm™ VanR Assay

| Submitted by: | BD Diagnostics (GeneOhm Sciences, Inc.)<br>7 Loveton Circle, Mail Code 614<br>Sparks, MD 21152, USA |
|----------------------|-----------------------------------------------------------------------------------------------------|
| Contact: | Raymond J. Boulé<br>Director, Regulatory Affairs<br>Molecular 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, Vancomycin<br>Resistant Bacteria, Direct Specimen |
| Predicate Device: | Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV)<br>(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.

{2}------------------------------------------------

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).

{3}------------------------------------------------

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 with<br>vanA<br>Genotype | VRE with<br>vanB<br>Genotype | VRE with<br>vanA and<br>vanB<br>Genotype | Negative | Total |
| BD GeneOhm™VanR<br>Results | 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 with<br>vanA<br>Genotype | VRE with<br>vanB<br>Genotype | VRE with<br>vanA and<br>vanB<br>Genotype | Negative | Total |
| BD GeneOhm™VanR<br>Results | 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<br>(95% CI') | Specificity<br>(95% CI') | VRE Prevalence | PPV<br>(95% CI') | NPV<br>(95% CI') |
|------|---------------------------------------|-----------------------------------------|---------------------|---------------------------------------|-------------------------------------------|
| vanA | 88.2%<br>(134/152)<br>(81.9% - 92.8%) | 96.6%<br>(1124/1164)<br>(95.3% - 97.5%) | 11.1%<br>(152/1372) | 77.0%<br>(134/174)<br>(70.0% - 83.0%) | 98.4%<br>(1124/1142)<br>(97.5% - 99.1%) |
| vanB | 100.0%<br>(3/3)<br>(29.2% - 100.0%) | 87.6%<br>(1150/1313)<br>(85.7% - 89.3%) | 0.2%<br>(3/1372) | 1.8%<br>(3/166)<br>(0.4% - 5.2%) | 100.0%<br>(1150/1150)<br>(99.7% - 100.0%) |
| VanR | 92.9%<br>(144/155)<br>(87.7% - 96.4%) | 86.0%<br>(998/1161)<br>(83.8% - 87.9%) | 11.3%<br>(155/1372) | 46.9%<br>(144/307)<br>(41.2% - 52.7%) | 98.9%<br>(998/1009)<br>(98.1% - 99.5%) |

' Binomial 95% exact confidence intervals.

{4}------------------------------------------------

Table 2B. Rectal Specimens

| | Sensitivity<br>(95% CI¹) | Specificity<br>(95% CI¹) | VRE Prevalence | PPV<br>(95% CI¹) | NPV<br>(95% CI¹) |
|------|---------------------------------------|---------------------------------------|--------------------|---------------------------------------|-----------------------------------------|
| vanA | 86.4%<br>(108/125)<br>(79.1% - 91.9%) | 96.1%<br>(681/709)<br>(94.3% - 97.4%) | 15.4%<br>(133/863) | 79.4%<br>(108/136)<br>(71.6% - 85.9%) | 97.6%<br>(681/698)<br>(96.1% - 98.6%) |
| vanB | 100.0%<br>(7/7)<br>(59.0% - 100.0%) | 82.5%<br>(682/827)<br>(79.7% - 85.0%) | 1.0%<br>(9/863) | 4.6%<br>(7/152)<br>(1.9% - 9.3%) | 100.0%<br>(682/682)<br>(99.5% - 100.0%) |
| VanR | 93.1%<br>(122/131)<br>(87.4% - 96.8%) | 82.2%<br>(578/703)<br>(79.2% - 85.0%) | 16.3%<br>(141/863) | 49.4%<br>(122/247)<br>(43.0% - 55.8%) | 98.5%<br>(578/587)<br>(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.

{5}------------------------------------------------

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 with<br>vanA<br>Genotype | VRE with<br>vanB<br>Genotype | VRE with<br>vanA and<br>vanB<br>Genotype | Negative | Total |
| BD GeneOhm™VanR<br>Results | 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 |

{6}------------------------------------------------

| Table 4B. Rectal Specimens | | Direct Culture + Alternative PCR | | | | |
|----------------------------|---------------|----------------------------------|------------------------------|------------------------------------------|----------|-------|
| | | VRE with<br>vanA<br>Genotype | VRE with<br>vanB<br>Genotype | VRE with<br>vanA and<br>vanB<br>Genotype | Negative | Total |
| BD GeneOhm™VanR<br>Results | 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<br>(95% CI1) | Negative Percent Agreement<br>(95% CI1) |
|------|-----------------------------------------|-----------------------------------------|
| vanA | 92.4%<br>(109/118)<br>(86.0%-96.5%) | 94.7%<br>(1133/1196)<br>(93.3%-95.9%) |
| vanB | 100.0%<br>(1/1)<br>(2.5%-100.0%) | 87.4%<br>(1148/1313)<br>(85.5%-89.2%) |
| VanR | 95.0%<br>(113/119)<br>(89.3%-98.1%) | 83.9%<br>(1003/1195)<br>(81.7%-86.0%) |

1 Binomial 95% exact confidence intervals.

## Table 5B. Rectal Specimens

| | Positive Percent Agreement<br>(95% CI1) | Negative Percent Agreement<br>(95% CI1) |
|------|-----------------------------------------|-----------------------------------------|
| vanA | 91.5%<br>(97/106)<br>(84.5%-96.0%) | 94.9%<br>(689/726)<br>(93.0%-96.4%) |
| vanB | 100.0%<br>(7/7)<br>(59.0%-100.0%) | 82.5%<br>(681/825)<br>(79.8%-85.1%) |
| VanR | 95.5%<br>(107/112)<br>(89.9%-98.5%) | 81.0%<br>(583/720)<br>(77.9%-83.8%) |

1 Binomial 95% exact confidence intervals.

{7}------------------------------------------------

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<br>(95% CI1) | Negative Percent Agreement<br>(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<br>(95% CI1) | Negative Percent Agreement<br>(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<br>(95% CI1) | Negative Percent Agreement<br>(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.

{8}------------------------------------------------

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 [phone] or [phone] 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