VRESelect ™ is a selective and differential chromogenic medium, containing 8 µg/mL of vancomycin, for the qualitative detection of gastrointestinal colonization of vancomycin-resistant Enterococcus faecium (VREfm) and vancomycin-resistant Enterococcus faecalis (VREfs) and to aid in the prevention and control of vancomycin-resistant Enterococcus (VRE) in healthcare settings. The test is performed on rectal swabs or fecal specimens from patients to be screened for VRE colonization. VRESelect ™ is not intended to diagnose VRE infection nor to guide or monitor treatment of infection. Results can be interpreted after 24 to 28 hours incubation. Subculture to non-selective media (e.g., trypticase soy agar with 5% sheep blood) is needed for susceptibility testing and epidemiological typing.

Device Description

VRESelect ™ is a selective medium for the detection of vancomycin-resistant Enterococcus (VRE). The selectivity of this medium is based on the presence of an antifungal/antibiotic mixture that inhibits the growth of most yeast, Gram negative and Gram positive bacteria, with the exception of vancomycin-resistant Enterococci (VRE).

Detection is based on the cleavage of chromogenic substrates by specific enzymes of Enterococcus faecium which produces pink colonies and Enterococcus faecalis which produces blue colonies.

Enterococcus gallinarum and Enterococcus casseliflavus are intrinsically resistant to vancomycin and may grow on the VRESelect™ medium as colorless or white colonies because they do not metabolize the chromogenic substrates. Vancomycin susceptible enterococci are inhibited.

After 24 to 28 hours incubation pink colonies can be reported as VREfm. Blue colonies should be confirmed by a catalase test and susceptibility (refer to limitation 9 in package insert).

AI/ML Overview

K122187: VRESelect™ Media Acceptance Criteria and Performance Study

The VRESelect™ Media is a selective and differential chromogenic medium intended for the qualitative detection of gastrointestinal colonization of vancomycin-resistant Enterococcus faecium (VREfm) and Enterococcus faecalis (VREfs).

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for VRESelect™ Media are not explicitly stated as numerical thresholds in this document. However, performance is assessed through comparison with a predicate device (BEAV + Confirmation) and established laboratory methods (Biochemical identification (Vitek) and Vancomycin minimal inhibitory concentration (MIC) by E-Test). The implicit acceptance criteria appear to be high levels of positive and negative agreement with these reference methods.

Metric	Acceptance Criteria (Implicit)	Reported Device Performance (24 hours)	Reported Device Performance (28 hours)
Method Comparison (vs. BEAV + Confirmation)
% Positive Agreement	High agreement	96% (182/189, [0.92, 0.98])	98% (186/189, [0.95, 0.99])
% Negative Agreement	High agreement	96% (727/757, [0.94, 0.97])	95% (721/757, [0.93, 0.96])
Biochemical Identification (vs. Vitek)
VREfm
% Positive Agreement	High agreement	94% (171/181, [0.90, 0.97])	97% (175/181, [0.93, 0.99])
% Negative Agreement	High agreement	97% (740/765, [0.95, 0.98])	96% (734/765, [0.94, 0.97])
VREfs
% Positive Agreement	High agreement	94% (15/16, [0.70, 0.99])	94% (15/16, [0.70, 0.99])
% Negative Agreement	High agreement	98% (910/930, [0.97, 0.99])	98% (909/930, [0.97, 0.99])
Vancomycin Resistance (vs. E-Test)
VREfm
% Positive Agreement	High agreement	96% (171/178, [0.92, 0.98])	98% (175/178, [0.95, 0.99])
% Negative Agreement	High agreement	97% (743/768, [0.95, 0.98])	96% (737/768, [0.94, 0.97])
VREfs
% Positive Agreement	High agreement	100% (12/12, [0.82, 1.00])	100% (12/12, [0.82, 1.00])
% Negative Agreement	High agreement	98% (911/934, [0.96, 0.99])	97% (910/934, [0.96, 0.98])

The conclusion states that "The VRESelect™ showed high diagnostic sensitivity and accuracy in this study," indicating that the reported performance met the sponsor's internal acceptance criteria.

2. Sample Size and Data Provenance for the Test Set

Sample Size: 946 stool samples were used for the method comparison study.
Data Provenance: The document does not explicitly state the country of origin for the samples. It also doesn't specify if the samples were retrospective or prospective, though the nature of a method comparison study often implies prospectively collected samples or a mixed approach.

3. Number of Experts and Qualifications for Ground Truth for the Test Set

The document does not specify the number of individual experts involved in establishing the ground truth for the test set. However, it indicates these processes:

For the Method Comparison Study (vs. BEAV + Confirmation): It states "confirmatory testing (Gram stain, catalase, PYR, Vitek 2 identification and vancomycin (MIC E-Test))." This implies established laboratory protocols and potentially certified laboratory personnel rather than individual "experts" in the sense of clinical specialists.
For Biochemical identification (Vitek) and Vancomycin minimal inhibitory concentration (MIC) (E-Test): These are standard laboratory methods with established protocols.

No specific qualifications (e.g., "radiologist with 10 years of experience") are mentioned for these individuals, as the ground truth relies on recognized laboratory tests rather than expert interpretation of images or clinical findings.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method in the context of multiple human readers or interpretations. The ground truth for the test set was established through a combination of a predicate device (BEAV) and a series of confirmatory laboratory tests (Gram stain, catalase, PYR, Vitek 2 identification, and vancomycin (MIC E-Test)). These are objective laboratory procedures, which typically do not involve an "adjudication" process in the same way clinical interpretations might.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not performed. The study evaluates the performance of the VRESelect™ medium itself against established laboratory methods, not how human readers improve with or without AI assistance. The device is a culture medium, not an AI or human-assisted diagnostic tool in the typical sense of an MRMC study.

6. Standalone Performance Study

Yes, a standalone performance study was done. The entire document describes the performance of the VRESelect™ media (the algorithm/device only, without human interpretation beyond reading the colonies) against established ground truth methods. The results are presented as agreement percentages.

7. Type of Ground Truth Used

The ground truth used was a combination of:

Predicate Device Performance: The results from the current standard, "BEAV plus Confirmation."
Laboratory Diagnostic Tests: This includes Gram stain, catalase, PYR, Vitek 2 identification, and vancomycin (MIC E-Test) for bacterial identification and resistance determination. This aligns with what can be considered definitive laboratory methods/gold standard diagnostic tests.

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or "training data" in the context of machine learning model development. This is because VRESelect™ is a chromogenic culture medium, not an AI/machine learning algorithm that requires training. Its performance is based on biochemical reactions and enzymatic activity, which are inherent properties of the medium. The studies described are validation or verification studies, not training for an adaptive algorithm.

However, if we interpret "training" in a broader sense of product development and optimization, the "limit of detection study" involving a panel of 18 vancomycin-resistant enterococci and the "challenge panel" of 56 well-characterized strains could be considered part of the development and refinement process, though not a "training set" for a learning algorithm.

9. How the Ground Truth for the Training Set (if applicable) was Established

As noted above, there is no explicit "training set" as understood in machine learning. For the studies that involved characterized strains (e.g., Limit of Detection, Challenge Panel), the ground truth for these strains would have been established through well-defined microbiological methods, including identification to species level and vancomycin susceptibility testing using standard laboratory techniques (e.g., AST methods like MIC E-Test or broth microdilution). The "ATCC reference strains" mentioned in the reproducibility study also serve as a form of "ground truth" with known characteristics.

Summary

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KIZZI87

510(k) SUMMARY

NOV 6 2012

Date of Summary

November 6, 2012

Product Name

Sponsor

VRESelect TM Media

Bio-Rad 3 Boulevard Raymond Poincaré 92430 Marnes-la-Coquette France

Correspondent

MDC Associates. LLC Fran White. Regulatory Consultant 180 Cabot Street Beverly. MA 01915

Substantially Equivalent Device

VRESelect ™ is substantially equivalent to the Thermo Fisher Scientific (formerly Remel) Spectra VRE Chromogenic Media (reference 510(k) K092819) and the Thermo Fisher Bile Esculin Azide Agar with 6ug/mL vancomycin (reference 510(k) K972359). The predicate device Package Inserts are included for reference (see Appendix II).

Thermo Fisher Scientific (formerly Remel) Manufacturer: Products: Spectra VRE Chromogenic Media Bile Esculin Azide Agar with 6ug/mL vancomycin

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Product Attribute	Intended use	Methodology	Inoculation	Sample Type	Substantial Equivalent
Bio-Rad VRESelect ™	VRE Select ™ is a selective and differential chromogenic medium, containing 8µg/mL of Vancomycin, for the qualitative detection of gastrointestinal colonization of vancomycin-resistant Enterococcus faecium (VRE fm ) and vancomycin-resistant Enterococcus faecalis (VRE fs ) and to aid in the prevention and control of vancomycin-resistant Enterococcus (VRE) in healthcare settings. The test is performed on rectal swabs or fecal specimens from patients to be screened for VRE colonization. VRE Select ™ is not intended to diagnose VRE infection nor to guide or monitor treatment of infection. Results can be interpreted after 24 to 28 hours incubation. Subculture to non-selective media (e.g., trypticase soy agar with 5% sheep blood) is needed for susceptibility testing and epidemiological typing.	Enzymatic	Direct or indirect	Rectal swabs or fecal specimens
Spectra VRE	Chromogenic mediaRemel Spectra VRE is a selective and differential chromogenic medium, containing 6µg/mL of Vancomycin, intended for use in the qualitative detection of gastrointestinal colonization with vancomycin-resistant Enterococcus faecium and Enterococcus faecalis (VRE) to aid in the prevention and control of VRE in healthcare settings. The test is performed with a rectal swab and fecal specimens from patients to screen for VRE colonization. Spectra VRE is not intended to diagnose VRE infection or to guide or monitor treatment for infections. Subculture to non-selective media (e.g. Tryptic Soy Agar with 5% sheep blood) is needed for further identification, susceptibility testing, and epidemiological typing.	Enzymatic	Direct specimen	Rectal swabs or fecal specimens	✓
Bile Esculin Azide Agar	Remel's Bile Esculin Azide Agar w/ 6µg/mL vancomycin is a plated medium recommended for use in qualitative procedures as a selective and differential medium for the primary isolation of vancomycin-resistant enterococci from surveillance cultures. This product is not intended for use as [a] method of antimicrobial susceptibility testing. Confirmation of resistance by an approved method is recommended as some organisms on initial isolation may overcome the inhibitory effects of the medium.	Enzymatic	Direct specimen	Fecal or urine specimens	✓

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Product Description

Detection is based on the cleavage of chromogenic substrates by specific enzymes of Enterococcus faecium which produces pink colonies and Enterococcus faecalis which produces blue colonies.

After 24 to 28 hours incubation pink colonies can be reported as VREfm. Blue colonies should be confirmed by a catalase test and susceptibility (refer to limitation 9 in package insert).

Intended Use

VRESelect ™ is a selective and differential chromogenic medium, containing 8μg/mL of vancomycin, for the qualitative detection of gastrointestinal colonization of vancomycin-resistant Enterococcus faecium (VREfm) and vancomycin-resistant Enterococcus faecalis (VREfs) and to aid in the prevention and control of VRE in healthcare settings. The test is performed on rectal swabs or fecal specimens from patients to be screened for VRE colonization. VRESelect ™ is not intended to diagnose VRE infection nor to guide or monitor treatment of infection. Results can be interpreted after 24 to 28 hours incubation. Subculture to non-selective media (e.g., trypticase soy agar with 5% sheep blood) is needed for susceptibility testing and epidemiological typing.

Performance Data

Interfering Substances

The following potential interfering substances were tested to confirm that they did not interfere with the performance of the VRESelect TM media:

Dulcolax®, Adult Glycerin Suppositories, Vaseline®, Preparation H®, Original . Boudreaux's Butt Paste®, Tuck's Medicated Cooling Pads®, Pepto-Bismol®, Miconazole cream, Nonoxynol-9 (spermicide), KY® Jelly, and Pepcid AC Max strength®.
Blood and Mucins .
Three commonly used transport media Amies without charcoal, Cary Blair. and LQ . Stuart

The interfering substances tested caused no significant differences between the number of colonies observed on the Control plates and the number of colonies observed on the VRESelect TM plates. The only exceptions were Tuck's Medicated Cooling Pads® (coloration delayed after

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24 hours with VREfm (ATCC 700221)) and Miconazole cream. The blood and mucins caused a delayed growth of one VREfs strain (ATCC 51299).

Cross Reactivity Testing (Analytical Specificity)

A cross-reactivity study was performed to determine if strains other than vancomycin-resistant enterococci could grow on VRESelect ™. One hundred thirty one (131) microorganisms representing Gram-negative rods, Gram-positive cocci, and yeasts were evaluated with the VRESelect ™. No cross-reactivity was observed with any strain tested. No variation was seen between 24 and 28 hour incubation time.

Limit of Detection Study

The minimum concentration of VRE reliably detected by VRESelect ™ is 103 CFU/mL.

To determine the percent recovery for the VRESelect ™ media a panel of eighteen vancomycinresistant enterococci - 8 VREfm and 10 VREfs - were tested at varying dilutions. For each strain to be tested a 0.5 McFarland suspension of the strain was prepared. A series of 10-fold serial dilutions in saline were carried out and inoculated onto three lots of VRESelect ™ plates and one lot of Blood Agar plates were incubated at 35-37℃ ambient air and read at 24 and 28 hours. The color and number of colonies were recorded. The Blood Agar plates were used to confirm the inoculum concentration at each dilution. Data confirmed that the minimum concentration of VRE reliably detected by VRESelect TM is 10 CFU/mL.

Reproducibility

In order to confirm the reproducibility of the VRESelect™ medium a blinded panel of 6 ATCC reference strains (2 VREfs, 3 VREfm, and 1 vancomycin-susceptible Enterococcus) were tested at three sites. At each site three technicians tested the panel on three lots of VRESelect™ each day for three days. The strains produced the expected results with VRESelect™ 100% of the time at 24 and 28 hours.

Challenge Panel

VRESelect ™ was evaluated with fifty-six (56) well-characterized strains including vancomycin-resistant and vancomycin-susceptible E. faecalis and E. faecium, as well as microorganisms commonly isolated from stool. All strains showed expected results.

Method Comparison

946 stool samples were tested on VRESelect ™ media (pink or blue colonies between 24 and 28 hours incubation) and BEAV (colonies with dark halos between 24 and 48 hours incubation) plus confirmatory testing (Gram stain, catalase, PYR, Vitek 2 identification and vancomycin (MIC E-Test) showed the following results.

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Table 1 BEAV +Confirmation vs. VRESelect™ results

		BEAV plus Confirmation
		% Positive Agreement	% Negative Agreement
VRESelect™	24 hours	96% (182/189, [0.92, 0.98])	96% (727/757, [0.94, 0.97])
	28 hours	98% (186/189, [0.95, 0.99])	95% (721/757, [0.93, 0.96])*

Thirty-three (33) of the 36 specimens that were BEAV plus Confirmation negative and that grew pink and/or blue colonies on VRESelect™ media, after subculture to blood agar plates (BAPs), were confirmed to be vancomycin resistant E. faecium and/or E. faecalis by biochemical identification and vancomycin E-Test. Three (3) specimens that were BEAV plus Confirmation negative and that grew pink and/or blue colonies on VRESelect™ media, after subculture to blood agar plates (BAPs), were not confirmed biochemical identification and vancomycin E-Test to be E. faecium and/or E. faecalis and represent false positive results.

VRESelect ™ (pink or blue colonies between 24 and 28 hours incubation) compared to samples identified as VREfm or VREfs using commercially available biochemical identification system demonstrated the following results.

Table 2

Biochemical identification (Vitek) vs. VRESelect™ results

	% Positive Agreement	% Negative Agreement
VREfm
VRESelect™ @ 24 hours	94% (171/181, [0.90, 0.97])	97% (740/765, [0.95, 0.98])
VRESelect™ @ 28 hours	97% (175/181, [0.93, 0.99])	96% (734/765, [0.94, 0.97])
VREfs
VRESelect™ @ 24 hours	94% (15/16, [0.70, 0.99])	98% (910/930, [0.97, 0.99])
VRESelect™ @ 28 hours	94% (15/16, [0.70, 0.99])	98% (909/930, [0.97, 0.99])

VRESelect ™ (pink or blue colonies observed between 24 and 28 hours incubation) compared to Vancomycin minimal inhibitory concentration (MIC) demonstrated the following results.

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· Table 3

Vancomycin Resistance vs. VRESelect™ results

	Vancomycin Resistance (E-Test)
	% Positive Agreement	% Negative Agreement
VREfm
VRESelect™ @ 24 hours	96% (171/178, [0.92, 0.98])	97% (743/768, 0.95, 0.98])
VRESelect™ @ 28 hours	98% (175/178, [0.95, 0.99])	96% (737/768, 0.94, 0.97])
VREfs
VRESelect™ @ 24 hours	100% (12/12, [0.82, 1.00])	98% (911/934, [0.96, 0.99])
VRESelect™ @ 28 hours	100% (12/12, [0.82, 1.00])	97% (910/934, [0.96, 0.98])

Conclusion

The VRESelect ™ showed high diagnostic sensitivity and accuracy in this study.

Statement of Safety and Efficacy

The data presented clearly demonstrates the safety and efficacy of the Bio-Rad VRESelect ™ for testing stool samples as compared to routine culture and identification when results are interpreted after 24 to 28 hours incubation.

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Image /page/6/Picture/0 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is circular, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the top half of the circle. In the center of the logo is a stylized image of an eagle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

Bio-Rad C/O Fran White, Regulatory Consultant MDC Associates, LLC 180 Cabot Street Beverly, MA 01915

6 2012 NOV

Re: K122187

Trade/Device Name: VRESelect™ Culture Medium Regulation Number: 21 CFR 866.1700 Regulation Name: Culture Medium for Antimicrobial Susceptibility Tests Regulatory Class: Class II Product Code: JSO Dated: October 10, 2012 Received: October 11, 2012

Dear Ms. White:

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 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 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

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Page 2 - Fran White

forth in the quality systems (QS) 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 Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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/cdrh/industrv/support/index.html.

Sincerely yours,

Sally A. Hojvat

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

Enclosure

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Indications for Use

412218 510(k) Number (if known):

Device Name:

VRESelect TM

Indications for Use:

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)

Nagaat
Division Sign Off

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

K122187 510(k)

Regulation Number and Section

§ 866.1700 Culture medium for antimicrobial susceptibility tests.

(a)
Identification. A culture medium for antimicrobial susceptibility tests is a device intended for medical purposes that consists of any medium capable of supporting the growth of many of the bacterial pathogens that are subject to antimicrobial susceptibility tests. The medium should be free of components known to be antagonistic to the common agents for which susceptibility tests are performed in the treatment of disease.(b)
Classification. Class II (performance standards).