VRESELECT CULTURE MEDIUM

K103684 · Bio-Rad · JSO · Oct 21, 2011 · Microbiology

Device Facts

• Record ID: K103684
• Device Name: VRESELECT CULTURE MEDIUM
• Applicant: Bio-Rad
• Product Code: JSO · Microbiology
• Decision Date: Oct 21, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1700
• Device Class: Class 2

Intended Use

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 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 further identification, susceptibility testing and epidemiological typing.

Device Story

VRESelect™ is a selective/differential chromogenic culture medium for identifying vancomycin-resistant Enterococcus (VRE) from rectal swabs. Medium contains 8 µg/mL vancomycin and antifungal/antibiotic agents to inhibit non-VRE flora. Principle of operation: enzymatic cleavage of chromogenic substrates by specific Enterococcus enzymes; VREfm produces pink colonies; VREfs produces blue colonies. Used in clinical microbiology laboratories; results interpreted visually by technicians after 24-28 hours incubation. Blue colonies require confirmatory catalase and susceptibility testing. Subculture to non-selective media required for further identification. Aids infection control by identifying VRE colonization in healthcare settings.

Clinical Evidence

Performance evaluated via method comparison study of 757 specimens against BEAV media and biochemical identification (Vitek 2). At 24-28 hours, VRESelect demonstrated high positive and negative agreement. For VREfm, positive agreement was 97-98% and negative agreement 97%. For VREfs, positive agreement was 79-82% and negative agreement 97%. Reproducibility confirmed with a blinded panel of 6 reference strains tested at 3 sites by 3 technicians, achieving 100% expected results. Analytical specificity tested against 119 microorganisms with no cross-reactivity observed. Minimum detection limit is 10^3 CFU/mL.

Technological Characteristics

Selective/differential chromogenic culture medium. Contains 8 µg/mL vancomycin and antifungal/antibiotic mixture. Principle: enzymatic cleavage of chromogenic substrates by specific Enterococcus enzymes. Form factor: plated medium. Incubation: 24-28 hours at 35-37°C. Manual interpretation of colony color (pink for E. faecium, blue for E. faecalis).

Indications for Use

Indicated for qualitative detection of gastrointestinal colonization with vancomycin-resistant Enterococcus faecium (VREfm) and Enterococcus faecalis (VREfs) in patients screened via rectal swabs. Not for diagnosing active infection or guiding/monitoring treatment.

Regulatory Classification

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.

Predicate Devices

• Spectra VRE Chromogenic Media (K092819)
• Bile Esculin Azide Agar with 6ug/mL vancomycin (K972359)

Submission Summary (Full Text)

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510(k) Submission K103684 Request for Additional Information VRESelect™ Culture Media Page 12 of 19

# OCT 2 1 2011

# 510(k) SUMMARY

# Date of Summary

October 19, 2011

Product Name

Sponsor

VRESelect ™ 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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510(k) Submission K 103684
Request for Additional Information
VRESelect™ Culture Media
Page 13 of 19

| | Spectra VRE | Bile Esculin Agar | Substantial Equivalent |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------|
| TM | Remel Spectra VRE is a selective and<br>differential chromogenic medium,<br>containing 6µg/mL of Vancomycin,<br>intended for use in the qualitative<br>detection of gastrointestinal<br>colonization with vancomycin-<br>resistant <i>Enterococcus faecium</i> and<br><i>Enterococcus faecalis</i> (VRE) to aid in<br>the prevention and control of VRE in<br>healthcare settings. The test is<br>performed with a rectal swab and fecal<br>specimens from patients to screen for<br>VRE colonization. Spectra VRE is not<br>intended to diagnose VRE infection or<br>to guide or monitor treatment for<br>infections. Subculture to non-selective<br>media (e.g. Tryptic Soy Agar with 5%<br>sheep blood) is needed for further<br>identification, susceptibility testing,<br>and epidemiological typing. | Remel's Bile Esculin Azide Agar w/<br>6µg/mL vancomycin is a plated<br>medium recommended for use in<br>qualitative procedures as a selective<br>and differential medium for the<br>primary isolation of vancomycin-<br>resistant enterococci from<br>surveillance cultures. This product is<br>not intended for use as [a] method of<br>antimicrobial susceptibility testing.<br>Confirmation of resistance by an<br>approved method is recommended as<br>some organisms on initial isolation<br>may overcome the inhibitory effects<br>of the medium. | |
| and<br>medium,<br>vancomycin,<br>of<br>of<br><i>Enterococcus</i><br>vancomycin-<br><i>faecalis</i><br>prevention<br>resistant<br>healthcare<br>on<br>to<br>infection.<br>to guide<br>after 24 to<br>subculture to<br>(trypticase<br>blood) is<br>and | | | ✓<br>✓ |
| | Enzymatic | Enzymatic | |
| | Direct specimen | Direct specimen | |

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510(k) Submission K103684
Request for Additional Information
VRESSelec/™ Culture Media
Page 14 of 19

| | The Matther Mand Company Company Collection Company Collection Comparis Comparent Collection Compress of Children Comparis of Children Comparis of Children Comparis of Childr<br>Rectal swabs | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------<br>ectal swabs or fecal specimer<br>The state of the state of the state of the status and the states of the states of the states of | Comments of the Comments of Children of Children Comments of Children<br>Fecal or urine specime | COCITION CONTINUE |
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510(k) Submission K103684 Request for Additional Information VRESelect™ Culture Media Page 15 of 19

### Product Description

VRESelect ™ is a selective medium for the detection of vancomyoin-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 facium which produces pink colonies and Enterococcus faecalis which produces blue colonies.

Enterococcus gallinarum and Enterocccus casseliflavus are intrinsically resistant to vancomycin and may grow on the VRESelect™ medium as colories 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 VRESm. Blue colonies should be confirmed by a catalase test and susceptibility testing (refer to limitation 8 in package insert).

#### Intended Use

VRESelect ™ is a selective and differential chromogenic medium, containing 8ug/mL of vancomycin, for the qualitative detection of gastrointestinal of vancomycin-resistant Enterococcus faccium (VREfm) and vancomycin-resistant Enterococcus faccalis (VREfs) and to aid in the prevention and control of VRE in healthcare settings. The test is performed on rectal swabs from patients to screen 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 need 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 ™ 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), K Y 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™ plates. The only exceptions were Tuck's Medicated Cooling Pads (coloration delayed after 24 hours with VREfm (ATCC 700221)) and Miconazole cream. The blood and mucins caused a delayed growth of one VREfs (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 nineteen (119) microorganisms representing Gram-negative rods, Grampositive 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.

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510(k) Submission K 103684 Request for Additional Information VRESelect™ Culture Media Page 16 of 19

#### Recovery 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 vancomycin-resistant 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°C 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 ™ is 103 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 vancomvcin-susceptible Enterococcus) were tested at three sites. At each site three technicians tested the panel on three lots of VRESelect™ each 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

757 specimens 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.

# Table 1

BEAV +Confirmation vs. VRESelect™ results

| | | BEAV +Confirmation | |
|------------|--------|-----------------------------|------------------------------|
| | | % Positive Agreement | % Negative Agreement |
| VRESelect™ | 24 hrs | 98% (118/120, [0.94, 1.00]) | 97% (615/637, [0.95, 0.98]) |
| | 28 hrs | 99% (119/120, [0.95, 1.00]) | 96% (610/637, [0.94, 0.97])* |

Ten of the 27 specimens that were BEAV plus confirmation negative and grew pink and/or blue colonies on VRESelect™ media, after subculture from VRESelect™ to Blood Agar Plates (BAPs), were confirmed as vancomycin-resistant E. faecium and/or E. faecalis by Vitek 2 biochemical identification and vancomycin E-Test. Seventeen specimens grew pink and/or blue colonies on VRESelect™ that were not confirmed by Viek 2 biochemical identification and vancomycin E-Test to be either vancomycin-resistant 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.

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510(k) Submission K103684 Request for Additional Information VRESelect™ Culture Media Page 17 of 19

## Table 2

Biochemical identification (Vitek) vs. VRESelect™ results

| | Vitek 2 Biochemical Identification | |
|------------------------|------------------------------------|------------------------------|
| | % Positive Agreement | % Negative Agreement |
| VREfm | | |
| VRESelectTM @ 24 hours | 97% (94/97, [0.91, 0.99]) | 97% (639/660, [0.95, 0.98]) |
| VRESelectTM @ 28 hours | 98% (95/97, [0.92, 0.99]) | 97% (639/660, [0.95, 0.98])* |
| VREfs | | |
| VRESelectTM @ 24 hours | 79% (30/38, [0.63, 0.89]) ** | 97% (696/719, [0.95, 0.98])† |
| VRESelectTM @ 28 hours | 82% (31/38, [0.66, 0.91]) | 97% (701/719, [0.96, 0.98]) |

ギ Twenty-one (21) specimens not identified as E. faecium on the study grew pink colonies on VRESelect™ media. 20 of those specimens, after subculture from VRESelect™ to BAPs, were confirmed as vancomycin-resistant E. faecium or E. faecium/E. faecalis by Vitek 2 biochemical identification and vancomycin E-Test. One specimen was determined to be false positive.

** Of the eight (8) specimens that were identified as E. faecalis by Vitek 2 biochemical identification and did not grow blue colonies on VRESelect™ media, six were shown to be vancomycin susceptible by the reference arm of the study. One specimen grew blue colonies on VRESelect™ after 28 hours and one specimen was determined to be false negative

ート Twenty-three (23) specimens not identified as E. faecalis on the reference arm of the study grew blue colonies on VRESelect™ media. Thirteen (13) of those specimens, after subculture from VRESelect to BAPs, were confirmed as vancomycin-resistant E. faecalis /E. faecium by Vitek 2 biochemical identification and vancomycin E-Test. Ten (10) specimens were found to be false positive (including 6 staphylococci catalase positive).

:

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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510(k) Submission K103684 Request for Additional Information VRESelect™ Culture Media Page 18 of 19

### Table 3

Vancomycin MIC vs. VRESelect™ results

| | Vancomycin Resistance (E-Test) | |
|------------------------|--------------------------------|-------------------------------|
| | % Positive Agreement | % Negative Agreement |
| VREfm | | |
| VRESelectTM @ 24 hours | 99% (93/94, [0.94, 0.99]) | 98% (626/637, 0.97, 0.99]) |
| VRESelectTM @ 28 hours | 100% (94/94, [0.95, 1.00]) | 98% (626/637, 0.97, 0.99])* |
| VREfs | | |
| VRESelectTM @ 24 hours | 96% (27/28, [0.81, 0.99]) | 98% (622/637, [0.96, 0.99]) |
| VRESelectTM @ 28 hours | 96% (27/28, [0.81, 0.99]) | 97% (617/637, [0.95, 0.98])** |

Note: Specimens that were identified in the reference arm of the study as vancomycin-resistant and identified as E. faecium or E. faecalis by Vitek 2 AND grew pink or blue colonies on VRESelect™ were considered in positive agreement.

* Eleven (11) specimens not identified as vancomycin-resistant on the reference arm of the study grew pink colonies on VRESelect™, the colonies which grew from 10 of those specimens, after subculture to a BAP, were confirmed to be vancomycin-resistant E. faecium by Vitek 2 biochemical identification and vancomycin E-Test. One specimen was determined to be false positive.

** Twenty (20) specimens not identified as vancomycin-resistant on the reference arm of the study grew blue colonies on VRESelect™. When colonies from those specimens were subcultured to BAPs five were identified as vancomycin-resistant E. faecium and 15 were not confirmed to be vancomycin-resistant E. faecalis / E. faecium, or were vancomycin-susceptible (including 8 staphylococci catalase positive).

# Conclusion

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

#### Statement of Safety and Efficacy

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

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Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the circumference. Inside the circle is a stylized symbol that resembles a human figure in profile, with three wavy lines emanating from the head, representing health and well-being.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

OCT 2 1 2011

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

Re: k103684

Trade/Device Name: VRESelect ™ Culture Medium Regulation Number: 21 CFR 866.1700 Regulation Name: Culture Media, Antimicrobial Susceptibility Test, Excluding Mueller Hinton Agar Regulatory Class: Class II Product Code: JSO Dated: October 19, 2011 Received: October 20, 2011

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 class II (Special Controls), 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

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# Page 2 - Ms. White

CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). 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 advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html,

Sincerely vours.

Yreddie Lu. Poole, ms

Sally 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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510(k) Submission K103684 Request for Additional Information VRESelect™ Culture Media Page 19 of 19

# Indications for Use

510(k) Number (if known): K103684

Device Name:

VRESelect ™ Culture Media

Indications for Use: J '

VRESelect ™ is a selective and differential chromogenic medium, containing 8 µg/mL of vancomycin, for the qualitative detection of gastrointestion 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 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 need for susceptibility testing and epidemiological typing.

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (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 Diagnostic Device Evaluation and Safety (OIVD)

Freddie h. Poole

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

510(k) K103684

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