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® 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 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 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.

Device Description

Following specimen lysis, amplification of the vanA and vanB targets occurs. Amplification of the IC, a DNA fragment of 294-bp including a 254-bp sequence not found in VRE, will also take place unless there are PCR inhibitory substances. The amplified DNA targets are detected with molecular beacons, a 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 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. For the detection of the Internal Control (IC) amplicons, the molecular beacon 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. The amount of fluorescence at any given cycle, or following cycling, 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.

AI/ML Overview

The GeneOhm Sciences Canada, Inc. IDI-VanR™ Assay is a qualitative in vitro test for the rapid detection of vancomycin-resistance (vanA and vanB) genes directly from rectal swabs, used as an aid to identify, prevent and control vancomycinresistant colonization in healthcare settings.

Here's an analysis of the provided text regarding acceptance criteria and the study that proves the device meets them:

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds that the device must meet. Instead, it presents the device's performance in comparison to a predicate device and culture technique, implying that substantial equivalence to the predicate (Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV)) serves as the primary "acceptance criterion" for market clearance.

However, based on the presented clinical performance data, we can infer the reported performance of the IDI-VanR™ Assay.

Acceptance Criteria (Inferred)	Reported Device Performance (Overall Study)
Substantial Equivalence to Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV) with phenotypic identification and resistance determination.	Clinical Performance with IDI-VanR™ Assay from Rectal Swabs vs. Culture Technique:- Overall Sensitivity: 97.3% (95% CI: 92.2%-99.4%)- Overall Specificity: 91.4% (95% CI: 89.3%-93.2%)- Negative Predictive Value (NPV): 99.6% (95% CI: 98.9%-99.9%)- Positive Predictive Value (PPV): 59.1% (95% CI: 51.6%-66.4%)Detailed breakdown by gene (Table 1):- Sensitivity VanA': 97.1% (95% CI: 91.6-99.4%) (Note: VanA' includes vanA alone and vanA+B PCR results considered true positive where culture was vanA positive.)- Sensitivity VanB: 57.1% (95% CI: 1.8-90.1%) (Acknowledged as low due to low number of vanB positive specimens).- Specificity (combined for vanA, vanB, vanA+B, negative): 91.4% (This specificity seems to be derived from the overall calculation in Table 2, not solely from Table 1's detailed breakdown, as a direct calculation from Table 1's "Negative" row would be different if only negative cultures were considered.)Unresolved Rate:- Initial: 0.2% (2/968)- After repeat testing: 0.1% (1/968)

Acceptance Criteria (Inferred)

Reported Device Performance (Overall Study)

Substantial Equivalence to Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV) with phenotypic identification and resistance determination.

Clinical Performance with IDI-VanR™ Assay from Rectal Swabs vs. Culture Technique:- Overall Sensitivity: 97.3% (95% CI: 92.2%-99.4%)- Overall Specificity: 91.4% (95% CI: 89.3%-93.2%)- Negative Predictive Value (NPV): 99.6% (95% CI: 98.9%-99.9%)- Positive Predictive Value (PPV): 59.1% (95% CI: 51.6%-66.4%)Detailed breakdown by gene (Table 1):- Sensitivity VanA': 97.1% (95% CI: 91.6-99.4%) (Note: VanA' includes vanA alone and vanA+B PCR results considered true positive where culture was vanA positive.)- Sensitivity VanB: 57.1% (95% CI: 1.8-90.1%) (Acknowledged as low due to low number of vanB positive specimens).- Specificity (combined for vanA, vanB, vanA+B, negative): 91.4% (This specificity seems to be derived from the overall calculation in Table 2, not solely from Table 1's detailed breakdown, as a direct calculation from Table 1's "Negative" row would be different if only negative cultures were considered.)Unresolved Rate:- Initial: 0.2% (2/968)- After repeat testing: 0.1% (1/968)

Note on "Acceptance Criteria": In 510(k) submissions, the primary "acceptance criterion" is often substantial equivalence to a predicate device. The performance metrics presented are to demonstrate that the new device is as safe and effective as the predicate. While specific numerical targets might not be explicitly stated as "acceptance criteria," regulatory bodies assess if the presented performance is acceptable for the intended use and comparable to established methods.

Study Details:

Sample sizes used for the test set and data provenance:
- Total Sample Size: 968 rectal swab specimens.
- Data Provenance: Clinical trials were performed at four investigational sites. The country of origin is not explicitly stated for all sites, but the submitter is GeneOhm Sciences Canada, Inc., suggesting at least some Canadian sites. The study appears to be prospective as it evaluates the performance of the IDI-VanR™ Assay against culture technique in a clinical trial setting.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications for establishing the ground truth. The ground truth (comparator method) was the "Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV) with phenotypic identification of presumptive Enterococcus colonies and determination of vancomycin and teicoplanin resistance (CLSI, M7-A6 and M100-S15)." This implies that laboratory personnel trained in microbiology and following established clinical guidelines (MMWR, CDC, CLSI) performed the ground truth testing.
Adjudication method for the test set:
- The document does not describe a formal adjudication method (e.g., 2+1, 3+1). The ground truth was established by the predicate culture method, and the device's results were compared against this. Any discrepancies would typically be resolved by retesting or further investigation according to the study protocol, though this specific detail is not provided.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- This is not an AI/CAD device. The IDI-VanR™ Assay is a nucleic acid amplification test (real-time PCR) for detecting specific genes. Therefore, an MRMC study with human readers and AI assistance is not applicable to this device.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance presented is for the device operating stand-alone. The IDI-VanR™ Assay is an in vitro diagnostic test, and its results (positive/negative for vanA/vanB) are generated by an automated real-time PCR instrument and software. The reported sensitivity and specificity refer to the device's performance as a primary diagnostic tool against the reference method.
The type of ground truth used:
- The ground truth used was culture technique (Remel Bile Esculin Azide agar with vancomycin) combined with phenotypic identification of Enterococcus colonies and determination of vancomycin and teicoplanin resistance according to established clinical and laboratory standards (MMWR, CDC, CLSI M7-A6 and M100-S15). This is a well-accepted and standard method for identifying VRE.
The sample size for the training set:
- The document does not mention a training set. This is typical for in vitro diagnostic tests like PCR assays. These types of assays are based on established molecular biology principles and validated against known controls and clinical samples without a "training set" in the machine learning sense. The assay's parameters (e.g., primer and probe design, cycling conditions) would be developed and optimized in a lab setting, not through machine learning training on a large dataset.
How the ground truth for the training set was established:
- As there is no mention of a training set, this question is not applicable. The assay's fundamental design is based on known genetic sequences (vanA and vanB) and molecular detection methods, not on data-driven training. Development would involve extensive analytical validation using characterized bacterial strains and clinical samples to optimize performance characteristics.

Summary

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K 061 t 86

AUG 8 9 2006

510(k) Summary

August 23, 2006

GeneOhm Sciences Canada, Inc. IDI-VanR™ Assay

Submitted by:	GeneOhm Sciences Canada, Inc.2050, boul. René-Lévesque O, 4º étageSainte-Foy, QuébecCanadaG1V 2K8
Contact:	Patricia Dionne, Ph.D.
Name of Device:Trade Name:Common Name:Classification Name:	IDI-VanR™ AssayVancomycin-resistant Enterococci detection assaySystem, 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 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.

Test Description:

The amplified DNA targets are detected with molecular beacons, a 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 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. For the detection of the Internal Control (IC) amplicons, the molecular beacon contains the fluorophore TET

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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 at any given cycle, or following cycling, 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.

Substantial Equivalence:

The GeneOhm Sciences Canada, Inc. IDI-VanR™ Assay has been found to be substantially equivalent to the Remel Bile Esculin Azide agar with 6 ug/mL vancomycin (BEAV) (K972359) with phenotypic identification of presumptive Enterococcus colonies (MMWR, 1995; CDC, 1999) and determination of vancomycin and teicoplanin resistance (CLSI, M7-A6 and M100-S15) for the detection of vancomycin resistance in presumptively identified cultures of Enterococcus faecalis and Enterococcus faecium.

Clinical trial were performed at four sites to evaluate the performance of the IDI-VanR™ Assay to the Remel Bile Esculin Azide agar with 6 ug/mL vancomvcin (BEAV) with phonotypic identification of presumptive Enterococcus colonies and determination of vancomycin and teicoplanin resistance. The results are summarized in Tables 1-3.

		IDI-VANRTM
		VANA	VANB	VANA+B	NEGATIVE	UNRESOLVED	TOTAL
Culture	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

Table 1: Clinical Performance Obtained for vanA and van B with IDI-VanR™ Assay from Rectal Swabs for the Overall Study in Comparison with Culture Technique

Sensitivity VanA': 97.1% (91.6-99.4%) Sensitivity VanB: 57.1% (1.8-90.1%)

Specificity: 91.4%

Sensitivity VanB: 57.1% (1.8-90.1%)

The vanA+B PCR results and culture vanA positive were considered as true positive and included in the calculation of the sensitivity of vanA target.

The low sensitivity associated with vanB detection is due to the low number of vanB positive specimens.

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		IDI-VANR TM
		POSITIVE	NEGATIVE	UNRESOLVED	TOTAL
Culture	Positive	107	3	0	110
	Negative	74	783	1	858
	Total :	181	786	1	968

Table 2: Clinical Performance Obtained with IDI-VanR™ Assay from Rectal Swabs for the Overall Study in Comparison with Culture Technique

Sensitivity: 97.3 (92.2%-99.4%)

Specificity: 91.4% (89.3%-93.2%)

3: Clinical Performance Obtained with IDI-VanR™ From Rectal Swabs by Each Table Investigational Site and For the Overall Study In Comparison With Culture Technique

Site	Clinical sensitivity ofIDI-VanR™	Clinical specificity IDI-VanR™ (95% CI)A	Initial	After repeattesting
Site #1	98.4%(91.2%-100%)	87.1%(81.6%-91.5%)	0.8%(2/255)	0.4%(1/255)
Site #2	100%(2.5-100%)	87.3%(81.3%-92.0%)	0%	N/A
Site #3	100%(2.5-100%)	92.0%(87.4%-95.4%)	0%	N/A
Site #4	95.7%(85.5%-99.5%)	96.0%(93.0%-97.9%)	0%	N/A
Overall study	97.3%(92.2%-99.4%)	91.4%(89.3%-93.2%)	0.2%(2/968)	0.1%(1/968)

A Binomial 95% confidence intervals

For the population tested, the negative predictive value was 99.6% (98.9%-99.9%) and the positive predictive value was 59.1% (51.6%-66.4%).

The low PPV is associated with vanB detection which is due to the low number of vanB positive specimens.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo features a stylized eagle with three tail feathers. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES . USA" are arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

AUG 3 0 2006

GeneOhm Sciences Canada, Inc. c/o Ms. Judi Smith Submission Correspondent Sienna Partners, LLC P.O. Box 103 Baldwin, Maryland 21082

K061686 Trade/Device Name: IDI-VanR® Assay Regulation Number: 21 CFR § 866.1640 Regulation Name: System test genotypic detection - resistant markers Regulatory Class: II Product Code: NIJ Dated: August 23, 2006 Received: August 24, 2006

Dear Ms. Smith:

Re:

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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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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, 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). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours.

Sally, autry

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

510(k) Number (if known): K061686

Device Name: IDI-VanR® Assay

Indications For Use:

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Loddie My Poole

Division Sign-Off

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Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K061686

Regulation Number and Section

§ 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).