← Product Code [NIJ](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/NIJ) · K061686

# IDI-VANR ASSAY (K061686)

_Geneohm Sciences Canada, Inc. · NIJ · Aug 30, 2006 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/NIJ/K061686

## Device Facts

- **Applicant:** Geneohm Sciences Canada, Inc.
- **Product Code:** [NIJ](/submissions/MI/subpart-b%E2%80%94diagnostic-devices/NIJ.md)
- **Decision Date:** Aug 30, 2006
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.1640
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for Use

The IDI-VanR® Assay is a qualitative in vitro test for the rapid detection of vancomycinresistance (vanA and vanB) genes directly from rectal swabs. The IDI-vanR® Assav 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 realtime PCR instrument with rectal swabs from patients at risk for VRE colonization. The IDI-VanR® Assay can be used as an aid to identify, prevent and control vancomycinresistant colonization in healthcare settings. Concomitant cultures are necessary to recover ofganisms for epidemiological typing, susceptibility testing and for further confirmatory identification. The IDI-VanR® Assay is not intended to diagnose VRE infections nor to guide or monitor treatment for VRE infections.

## Device Story

The IDI-VanR Assay is an in vitro diagnostic test for detecting vanA and vanB genes in rectal swabs. Input consists of rectal swab specimens; processing involves specimen lysis followed by real-time PCR amplification of target genes and an internal control. Detection utilizes molecular beacons—hairpin-forming oligonucleotides labeled with fluorophores (FAM for vanA, Texas Red for vanB, TET for internal control) and a DABCYL quencher. In the presence of target DNA, hybridization opens the beacon, emitting fluorescence. The SmartCycler instrument monitors fluorescence in real-time; software interprets data to provide results. Used in healthcare settings to aid in VRE colonization control; requires concomitant cultures for confirmation and susceptibility testing. Results assist clinicians in identifying colonized patients for infection control measures.

## Clinical Evidence

Clinical trial at four sites (n=968) compared IDI-VanR Assay to culture-based phenotypic identification. Overall sensitivity for vanA was 97.1% and vanB was 57.1% (low sensitivity due to low prevalence of vanB). Overall sensitivity for VRE detection was 97.3% (95% CI: 92.2%-99.4%) and specificity was 91.4% (95% CI: 89.3%-93.2%). Negative predictive value was 99.6%; positive predictive value was 59.1%.

## Technological Characteristics

Real-time PCR assay using molecular beacon technology. Targets: vanA, vanB, and internal control DNA. Detection via fluorophore-quencher labeled oligonucleotides (FAM, Texas Red, TET). Instrument: SmartCycler. Qualitative in vitro diagnostic test.

## Regulatory 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](/device/K972359.md))

## Submission Summary (Full Text)

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>
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
K061686

B. Purpose for Submission:
To detect vanA and vanB genes in rectal swabs

C. Measurand:
vanA and vanB genes

D. Type of Test:
Qualitative Nucleic Acid Amplification Test of the vanA and vanB genes directly from rectal swabs.

E. Applicant:
GeneOhm Sciences Canada Inc.

F. Proprietary and Established Names:
IDI-VanR™ Assay

G. Regulatory Information:
1. Regulation section:
866.1640
2. Classification:
II
3. Product code:
NIJ – System, test, genotypic detection, resistant markers
4. Panel:

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## H. Intended Use:

1.  Intended use(s):
The IDI-VanR® Assay is a qualitative in vitro test for the rapid detection of vancomycin-resistance (*vanA* and *vanB*) genes directly from rectal swabs. The IDI-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 rectal swabs from patients at risk for VRE colonization. The IDI-VanR® Assay can be used as an aid to identify, prevent and control vancomycin-resistant colonization in healthcare settings. Concomitant cultures are necessary to recover organisms for epidemiological typing, susceptibility testing and for further confirmatory identification. The IDI-VanR® Assay is not intended to diagnose VRE infections nor to guide or monitor treatment for VRE infections.

2.  Indication(s) for use:
The IDI-VanR® Assay is a qualitative in vitro test for the rapid detection of vancomycin-resistance (*vanA* and *vanB*) genes directly from rectal swabs. The IDI-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 rectal swabs from patients at risk for VRE colonization. The IDI-VanR® Assay can be used as an aid to identify, prevent and control vancomycin-resistant colonization in healthcare settings. Concomitant cultures are necessary to recover organisms for epidemiological typing, susceptibility testing and for further confirmatory identification. The IDI-VanR® Assay is not intended to diagnose VRE infections nor to guide or monitor treatment for VRE infections.

3.  Special conditions for use statement(s):
Samples must be collected using the Copan Transystem™ swabs. (Liquid Stuart, Liquid Amies, Amies Agar Gel without Charcoal, or Amies Agar Gel with Charcoal).

Prescription Use Only

4.  Special instrument requirements:
Assay is performed with the SmartCycler® instrument

## I. Device Description:

The IDI-VanR™ Assay is performed on rectal swabs with a procedure that includes

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specimen lysis, amplification of the vanA and vanB targets, and detection of fluorogenic target-specific hybridization probes. The amplification, detection and interpretation of the signals are done automatically by the Cepheid SmartCycler® instrument software. A positive and negative control is included in each IDI-vanR™ Assay run. An Internal Control is also included in each assay tube. The inclusion of these three controls will monitor every step of the PCR procedure and the functionality of every reagent. External controls are recommended to monitor the cell lysis and DNA extraction steps. The procedure takes about 60 to 75 minutes.

# J. Substantial Equivalence Information:

1. Predicate device name(s):

Bile Esculin Azide agar with  $6\mu \mathrm{g / mL}$  vancomycin

2. Predicate 510(k) number(s):

K972359

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Intended Use | Screening for vancomycin resistance | Same  |
|  Type of test | Qualitative | Same  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device | Predicate  |
|  Technology | PCR amplification with detection of fluorogenic target-specific hybridization | Growth based phenotypic detection  |
|  Controls | Positive, negative and internal controls are part of the assay. Specimen processing controls are recommended which include positive and negative Enterococci spp. isolates | E. faecalis ATCC 51299 - positive; E. faecalis ATCC 29212 - negative  |
|  Mode of detection | Presence of vanA and or vanB genes | Growth or no growth in the presence of 6 μg/mL vancomycin  |
|  Specimen Type | Rectal swab | Rectal swab or stool  |

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K. Standard/Guidance Document Referenced (if applicable):

Not Applicable

L. Test Principle:

Following specimen lysis and vanA and vanB amplification, the DNA targets are detected with molecular beacons, a hairpin-forming single-stranded oligonucleotides labeled as tone 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 vanA amplicons, the molecular beacon 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 the vanB amplicons, the molecular beacon contains the fluorophore Texas Red 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. The amount of fluorescence depends on the amount of specific amplicons present at that time. The SmartCycler® software simultaneously monitors the fluorescence emitted by each beacon, interprets all data, and provides a final result at the end of the cycling program.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Ten samples containing negative matrix consisting of 3 low positive specimens and 5 high positive specimens and a negative and positive control were frozen and sent to three sites. Testing was performed in triplicate on three separate days at each site with three lots. Both vanA and vanB genes were included to ensure that all primers and probes of the IDI-vanR™ Assay were assessed. The overall reproducibility was >95% with 3 invalid positive control results.

b. Linearity/assay reportable range:

Not Applicable

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

The table below describes internal controls that are part of the assay with the various parts controlled.

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|  Step controlled |   | Positive Control | Negative Control | Internal Control  |
| --- | --- | --- | --- | --- |
|  Specimen Preparation | Cell lysis |  |  |   |
|   |  DNA extraction |  |  |   |
|   | Inactivation of heat labile inhibitors |  | X | X  |
|  PCR | Denaturation step | X |  | X  |
|   |  Primer/target annealing | X |  | X  |
|   |  Elongation Step | X |  | X  |
|   | Probe/amplicon annealing | X |  | X  |
|  Presence of non heat labile PCR inhibitors |   |  |  | X  |
|  Reagent contamination |   |  | X |   |
|  Environmental contamination with GBS amplicon |   |  | X |   |

Since Cell lysis and DNA extraction are not controlled, the Package Insert will carry a statement that the user may test a positive and negative strain as recommended or required by other regulations. The recommendations include the testing of ATCC 51299 E. faecalis as a positive specimen processing control and for E. gallinarum ATCC 700425 as an external negative control.

d. Detection limit:

Internal studies determined that the genomic limits of detection (LOD) for specific vanA and vanB are 5 and 10 DNA copies per reaction, respectively. The bacterial LOD for vanA and vanB are 1.6 and 1.4 CFU/reaction.

e. Analytical specificity:

Analytical specificity of the IDI-vanR™ Assay was determined with well-characterized isolates of vancomycin-sensitive closely related genera, and other pathogenic and commensal flora found in the rectum and stools. These included Enterococcus spp. with the presence of other van genes (vanC, vanD, vanE, vanG). All provided a negative test result.

Potentially interfering substances were tested using materials that may be found in the rectum (petroleum jellies, creams, blood, suppositories). Blood showed a reduction in the IC% Endpoint and hydrocortisone provided unresolved results when the swab was heavily covered in it.

f. Assay cut-off:

Acceptance Criteria for the IDI-VanR™ were established during assay development and pre-validated at one external site with 216 specimens prior to the clinical trial. The acceptance criteria includes; Endpoint threshold, 2nd derivative threshold, minimum cycle threshold, maximum cycle threshold, and % IC NC endpoint.

2. Comparison studies:

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a. Method comparison with predicate device:

A clinical study was conducted at 4 diverse sites from units with high VRE prevalence such as intensive care units. Each site performed routine VRE screening (culture on selective media [Bile Esculin azide agar with  $6\mu \mathrm{g / mL}$  vancomycin (BEAV) plate) followed by phenotypic identification and detection of vancomycin and teicoplanin resistance]. An enriched culture method was also inoculated (Bile Esculin Azide broth with vancomycin 8  $\mu \mathrm{g / mL}$ ) and further cultured if the original culture was negative. A total of 968 rectal swab specimens were collected with one of the recommended swabs (refer to "Materials required but not provided"), screened for vancomycin-resistance with the reference culture method described above and with the IDI-VanR™ assay. Compared to the culture method, the IDI-VanR™ assay identified  $97.3\%$  of the positive specimens (by either culture technique), and  $91.4\%$  of the specimens negative (by both culture techniques). For the population tested, these results produced a negative predictive value of  $99.6\%$  and positive predictive value of  $59.1\%$ .

|   | IDI-VANR™ |   |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |  VAN A | VAN B | VAN A+B | NEGATIVE | UNRESOLVED | TOTAL  |
|  Reference Method | VanA | 80 | 0 | 18 | 3 | 0 | 101  |
|   |  VanB | 0 | 4 | 3 | 0 | 0 | 7  |
|   |  VanA + B | 0 | 0 | 2 | 0 | 0 | 2  |
|   |  Negative | 14 | 58 | 2 | 783 | 1 | 858  |
|   | Total : | 94 | 62 | 25 | 786 | 1 | 968  |

The IDI-vanR™ "vanB" only column in the table above would be recommended for further confirmation according to the interpretation of this result. Of the 62 vanB only positives, 4 were culture vanB positive with the rest not positive fro VRE by culture.

b. Matrix comparison:

Not Applicable

3. Clinical studies:

a. Clinical Sensitivity:

Not Applicable

b. Clinical specificity:

Not Applicable

c. Other clinical supportive data (when a. and b. are not applicable):

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Not Applicable

4. Clinical cut-off:
Not Applicable

5. Expected values/Reference range:
The prevalence of VRE in the study population was 11.1%. The overall vanA prevalence was 10.6% and vanB was 0.9%.

N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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**Source:** [https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/NIJ/K061686](https://fda.innolitics.com/submissions/MI/subpart-b%E2%80%94diagnostic-devices/NIJ/K061686)

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