(304 days)
Remel Spectra™ VRE is a selective and differential chromogenic medium, containing 6 µg/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 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.
Remel Spectra™ VRE is an opaque medium allowing differentiation of vancomycin-resistant E. faecium from vancomycin-resistant E. faecalis by incorporation of two chromogens that are targeted by phosphatase and agalactosidase. The action of these enzymes on the chromogens results in a build-up of color within the colony. The presence of phosphatase enzymes in both E. faecium and E. faecalis results in a light blue or blue colony. However, E. faecium also produces a-galactosidase, resulting in a mix of blué and pink chromophores within the bacterium producing navy blue or pink-purple colonies, which are distinquished from the light blue or blue E. faecalis colonies. Additional antibiotics. in combination with vancomycin, are present to suppress the growth of competing flora including E. gallinarum and E. casseliflavus, both of which are intrinsically resistant to vancomycin, possessing the chromosomally encoded VanC resistance mechanism.
The information provided describes the performance of the Spectra™ VRE device, a chromogenic medium for detecting VRE colonization. Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a section, but rather presents the overall agreement percentages for the device compared to conventional methods. The implicit acceptance criteria would likely be high concordance with established methods for both positive and negative results, along with robust detection of the target organisms.
| Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Spectra™ VRE vs. Conventional Methods) |
|---|---|---|
| Overall Performance | High agreement | Positive % Agreement: 99.1% (218/220) |
| Negative % Agreement: 99.8% (408/409) | ||
| VR-E. faecium Detection | High agreement | Positive % Agreement: 99.0% (189/191) |
| Negative % Agreement: 99.8% (437/438) | ||
| VR-E. faecalis Detection | High agreement | Positive % Agreement: 100% (29/29) |
| Negative % Agreement: 100% (600/600) | ||
| VRE Recovery (Spectra™ VRE vs. BEAV) | Higher or similar recovery | Spectra™ VRE: 99.1% (218/220) |
| BEAV: 95.5% (210/220) | ||
| Interfering Substances | Minimal interference | Some substances (e.g., blood, Pepto-Bismol®) may reduce recovery |
| Reproducibility | 100% consistency | 100% of tested strains produced expected results at 24 hours |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 623 prospective rectal swab and fecal surveillance specimens (yielding 629 data points).
- Data Provenance: The study was conducted at "three geographically diverse regions of the United States," indicating a multi-site prospective study within the US. The data is prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the "number of experts" or their "qualifications." It states that suspect VRE isolates were evaluated using:
- Vitek® 2 system
- Biochemical tests
- Antibiotic gradient method for vancomycin MIC determination
This suggests laboratory personnel following established microbiology protocols, rather than individual expert adjudication in the traditional sense of, for example, multiple radiologists reviewing images.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method in the context of resolving discrepancies between multiple readers or interpretations. The ground truth was established by a combination of standard laboratory methods (Vitek® 2, biochemical tests, MIC determination), which inherently provide a definitive result without a need for "adjudication" between conflicting interpretations by multiple individuals.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. The study compares the performance of the Spectra™ VRE medium to a conventional culture method (Bile Esculin Azide Agar with Vancomycin), not the comparative effectiveness of human readers with or without AI assistance. The interpretation of both the Spectra™ VRE and the conventional method is described as "Manual, visual," indicating human interpretation of culture plates, but not a study designed to measure the impact of AI assistance on human performance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
This is an in vitro diagnostic (IVD) device, specifically a culture medium. Its performance is inherent to how well it grows and differentiates bacteria under manual, visual interpretation. There is no "algorithm" in the sense of artificial intelligence that would perform autonomously. Therefore, the concept of a "standalone" algorithm performance (without human-in-the-loop) as understood in AI/ML medical devices does not apply here. The performance described is the standalone performance of the medium itself when interpreted manually.
7. The Type of Ground Truth Used
The ground truth was established by a combination of:
- Conventional Culture: Growth on Bile Esculin Azide Agar with 6 µg/ml Vancomycin (BEAV) after 48 hours incubation.
- Identification and Susceptibility Testing: Suspect isolates were further evaluated using the Vitek® 2 system, biochemical tests, and an antibiotic gradient method for vancomycin Minimum Inhibitory Concentration (MIC) to confirm VRE (specifically E. faecium and E. faecalis) with MICs >256 µg/ml.
This represents a form of "reference standard" based on established microbiology laboratory methods for identification and antimicrobial susceptibility testing.
8. The Sample Size for the Training Set
The document does not mention a "training set" or "training data" as this is not an artificial intelligence/machine learning device. The development of the chromogenic medium would involve laboratory R&D, but not in the sense of training an algorithm on a dataset.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the context of an AI/ML device, this question is not applicable. The development of the medium would rely on scientific principles of microbiology and chromogenic reactions to achieve the desired differentiation.
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510(k) SUMMARY
Contact Information: Mary Ann Silvius Director. New Product & Business Development Microbiology North America Thermo Fisher Scientific Remel Products 12076 Santa Fe Drive Lenexa. KS 66215 Phone: (913) 895-4054 Fax: (913) 895-4054 email: maryann.silvius@thermofisher.com
JUL 1 5 2010
- Date Prepared: September 11, 2009
- Device Trade Name: Spectra™ VRE
- Predicate Device: Remel Bile Esculin Azide Aqar with 6 uq/ml Vancomycin
Device Classification: 21 CFR 866.1700: Culture medium for antimicrobial susceptibility tests.
- Remel Spectra™ VRE is a selective and differential Intended Use: chromogenic medium, containing 6 µg/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 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 Sov Agar with 5% sheep blood) is needed for further identification. susceptibility testing, and epidemiological typing.
- Device Description: Remel Spectra™ VRE is an opaque medium allowing differentiation of vancomycin-resistant E. faecium from vancomycin-resistant E. faecalis by incorporation of two chromogens that are targeted by phosphatase and agalactosidase. The action of these enzymes on the chromogens results in a build-up of color within the colony. The presence of phosphatase enzymes in both E. faecium and E. faecalis results in a light blue or blue colony. However, E. faecium also produces a-galactosidase, resulting in a mix of blué and pink chromophores within the bacterium producing navy blue or pink-purple colonies, which are distinquished from the light blue or blue E. faecalis colonies. Additional antibiotics. in combination with vancomycin, are present to suppress the growth of competing flora including E. gallinarum and E. casseliflavus, both of which are intrinsically resistant to vancomycin, possessing the chromosomally encoded VanC resistance mechanism.
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Device Comparison:
| Characteristic | Remel Spectra™ VRE | Remel Bile EsculinAzide with Vancomycin |
|---|---|---|
| Similarities | ||
| Intended Use | Remel Spectra™ VRE is a selective anddifferential chromogenic medium,containing 6 µg/ml of vancomycin,recommended for use in the qualitativedetection of gastrointestinal colonization ofvancomycin-resistant Enterococcus (VRE)to aid in the prevention and control of VREin healthcare settings. The test isperformed with rectal swabs and fecalspecimens from patients to screen for VREcolonization. Spectra™ VRE is notintended to diagnose VRE infection or toguide or monitor treatment for infections.Subculture to non-selective media (e.g.Tryptic Soy Agar with 5% sheep blood) isneeded for further identification,susceptibility testing, and epidemiologicaltyping. | Remel Bile Esculin Azide Agarw/ 6 µg/ml Vancomycin is asolid medium recommended foruse in qualitative procedures asa screening method for primaryisolation and presumptiveidentification of vancomycin-resistant enterococci (VRE)from surveillance cultures. |
| Inoculation | Direct Specimen | Direct Specimen |
| Sample Type | Fecal specimensRectal swabs | Fecal SpecimensUrine specimens |
| Interpretation | Manual, visual | Manual, visualAdditional confirmation required |
| TestMethodology | Enzymatic | Enzymatic |
| Incubation | 24 hours | 24-48 hours |
| Differences | ||
| TargetEnzyme | Phosphataseα-galactosidase | Esculin hydrolysis |
| SpeciesDifferentiation | Positive - Vancomycin-resistant E. faeciumcolonization: Navy blue or purple-pinkcolonies.Positive - Vancomycin-resistant E. faecaliscolonization: Light blue to blue colonies.Negative - No VRE colonization: Nocolored colonies | Positive - Dark brown to blackcolor around colonies anddiffusing into the medium.Negative - No blackening of themedia. |
Summary of Performance Data:
Clinical Accuracy:
The performance of Spectra™ VRE was evaluated at three geographically diverse regions of the United States. A total of six hundred twenty-three (623) prospective rectal swab and fecal surveillance specimens (yielding 629 data points) were evaluated. Results from Spectra™ VRE at 24 hours incubation were compared to results obtained from traditional culture on Bile Esculin Azide Agar with 6 µg/ml Vancomycin (BEAV) after 48 hours incubation. Two hundred twenty VRE with minimal inhibitory concentration MICs to vancomycin of >256 µg/ml were recovered from six hundred twenty three specimens (191 vancomycin-resistant E. faecium and 29
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vancomycin-resistant E. faecalis). The overall recovery of VRE on Spectra™ VRE at 24 hours was 99.1% (218/220) compared to recovery of 95.5% (210/220) on BEAV at 48 hours.
Suspect isolates of VRE were evaluated using the Vitek® 2 system and biochemical tests, and an antibiotic gradient method for determination of vancomycin MIC. For detection of VRE by colored colonies isolated on Spectra™ VRE at 24 hours compared to identification and susceptibility testing as described. the overall agreement was 99.5% (626/629).
| Positive % Agreement | Negative % Agreement | |
|---|---|---|
| Spectra™ VRE vs.conventional methods | 99.1% | 99.8% |
| (218/220) | (408/409) | |
| (95% CI = 96.8-99.9%) | (95% CI = 98.6-100%) |
Note : CI = Confidence Interval
Forty rectal swabs (eleven positive and twenty-eight negative) were tested which did not yield a statistically sound 95% lower bound confidence interval. The results are not included in the data.
Spectra™ VRE vs. Conventional Methods
| Positive % Agreement | Negative % Agreement | |
|---|---|---|
| VR-E. faecium | 99.0%(189/191)a(95% CI = 96.3-99.9%) | 99.8%(437/438)b(95% CI = 98.7-100%) |
| VR-E. faecalis | 100%(29/29)(95% CI = 88.1-100%) | 100%(600/600)(95% CI = 99.4-100%) |
Note : Cl = Confidence Interval
4 One isolate showed expected results at 28 hours and one isolate showed expected results at 48 hours.
6 One isolate developed pink colonies and was identified as Lactobacillus sp.
Performance Compared to Commercially Available Devices:
Spectra™ VRE was compared to culture on Bile Esculin Azide with 6 ug/ml Vancomycin, with subsequent identification and susceptibility testing. There was 82.7% (520/629) agreement with six hundred twenty-nine isolates. The Bile Esculin Azide with 6 ug/ml Vancomycin demonstrated 95.5% (210/220) agreement for the recovery of VRE (acquired resistance) and 75.8% (310/409) agreement for non-VRE.
Interfering Substances:
The following substances were evaluated for potential interference of the chromogenic reaction of Spectra™ VRE. These substances were tested in combination with vancomvcinresistant E. faecalis and E. faecium isolates at a concentration of 50 CFU: blood, mucous, MYLANTA® Maximum Strength, Pepto-Bismol®, Imodium® A-D, Kaopectate®, Fletcher's Castoria®, PEPCID® AC Maximum Strength, Tagamet HB 200®, Prilosec OTC®, vancomycin, metronidazole, barium sulfate, Preparation Ho, petroleum jelly, glycerin, bisacodyl, witch hazel, miconazole, nonoxynol-9, KY® Jelly. Hydrocortisone acetate was not evaluated. Blood, Pepto-Bismol®, glycerin, vancomycin, miconazole, and Preparation H® may reduce the recovery of vancomycin resistant E. faecalis and E. faecium strains.
Reproducibility:
Reproducibility testing was conducted at four sites on three separate days with twenty blinded strains including vancomycin susceptible and resistant E. faecium and E. faecalis, as well as quality control reference strains. The strains produced the expected result with Spectra™ VRE 100% of the time at 24 hours.
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Image /page/3/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird in flight, composed of three curved lines.
Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002
JUL 15 2010
ThermoFisher SCIENTIFIC Remel Products c/o Mary Ann Silvius Director, New Product & Business Development Microbiology North America 12076 Santa Fe Drive Lenexa, KS 66215
Re: K092819
Trade/Device Name: Spectra™ VRE Regulation Number: 21 CFR § 866.1700 Regulation Name: Remel Spectra™ VRE Chromogenic VRE Media Regulatory Class: Class II Product Code: . 180 Dated: July 13, 2010 Received: July 14, 2010
Dear Ms. Silvius
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, ilsting 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) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97).
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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html
Sincerely yours,
Saga Agona
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
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INDICATIONS FOR USE
510(k) Number (if known): K092819
Device Name: Spectra™ VRE
Indications For Use: Remel Spectra™ VRE is a selective and differential chromogenic medium, containing 6 µg/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 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.
Prescription Use (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (Part 21 CFR 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Ludolite. Rooly
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k)
§ 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).