BBL™ CHROMagar™ MRSA is a selective and differential medium for the qualitative direct detection of nasal colonization by methicillin resistant Staphylococcus aureus (MRSA) to aid in the prevention and control of MRSA infections in healthcare settings. The test is performed on anterior nares swab specimens from patients and healthcare workers to screen for MRSA colonization. BBL™ CHROMagar™ MRSA is not intended to diagnose MRSA infection nor to guide or monitor treatment for infections.

Device Description

The BBL CHROMagar MRSA medium permits the direct detection and identification of MRSA through the incorporation of specific chromogenic substrates and cefoxitin. The cephalosporin (Cefoxitin) is incorporated to select for methicillin resistant strains of Staphylococcus aureus. MRSA strains will grow in the presence of cefoxitin and produce mauve-colored colonies resulting from hydrolysis of the chromogenic substrate. Additional selective agents are incorporated for the suppression of gram-negative organisms, yeast and some gram-positive cocci. Bacteria other than MRSA may utilize other chromogenic substrates in the medium resulting in blue to blue/green colored colonies or if none of the chromogenic substrates are utilized, appear as white or colorless.

AI/ML Overview

This document describes the performance of the BBL™ CHROMagar™ MRSA (CMRSA) culture medium for the direct detection of methicillin-resistant Staphylococcus aureus (MRSA) from anterior nares swab specimens.

Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the BBL CHROMagar MRSA are not explicitly stated as numerical targets in the provided text, but rather implied by the achievement of sufficient performance for a 510(k) clearance and comparison to predicate devices and other methods. Based on the performance data presented, the implied criteria focused on high sensitivity and specificity. The "Performance" section under Analytical Studies mentions a sensitivity and specificity criteria of ≥90% was met for CMRSA compared to Oxacillin MIC testing and Oxacillin Screen Agar testing (with 48-hour incubation).

Metric / Comparison	Implied Acceptance Criteria (Based on Performance)	Reported Device Performance
Analytical Studies
Reproducibility (Inter-lot & Overall)	≥95% reproducibility rate	≥95% reproducibility rate achieved
Expression of Resistance (Heterogeneous & Homogeneous MRSA)	Adequate detection	Adequately detects both heterogeneous and homogeneous MRSA
Sensitivity vs. Oxacillin MIC	≥90%	Met
Specificity vs. Oxacillin MIC	≥90%	Met
Sensitivity vs. Oxacillin Screen Agar	≥90%	Met
Specificity vs. Oxacillin Screen Agar	≥90%	Met
Clinical Studies
Reproducibility (Across sites)	High reproducibility	100% across all three sites
Challenge Strain Testing (Detection of MSSA & MRSA)	Reliable detection	Reliably detected both at 100% (individual & across sites)
MRSA Overall Recovery vs. TSA II (Clinical Specimens)	Not explicitly stated as a target, but high recovery expected	95% (126/132)
Negative Agreement vs. Oxacillin MIC (Colony color + confirmation)	High negative agreement	99% (1829/1842)
% Agreement of MRSA vs. Oxacillin MIC	High agreement	95% (111/117)
% Agreement of MSSA vs. Oxacillin MIC	High agreement	97% (201/208)
Overall Category Agreement vs. Oxacillin MIC	High agreement	96% (312/325)
MRSA Overall Recovery vs. TSA (Clinical Specimens)	Not explicitly stated as a target, but high recovery expected	95% (125/131)
Negative Agreement vs. Oxacillin Screen Agar (Colony color + confirmation)	High negative agreement	99% (1830/1843)
% Agreement of MRSA vs. Oxacillin Screen Agar	Acceptable	95% (110/116)
% Agreement of MSSA vs. Oxacillin Screen Agar	Acceptable	97% (202/209)
Overall Category Agreement vs. Oxacillin Screen Agar	Acceptable	96% (312/325)
% Agreement of MRSA vs. Cefoxitin Disk Diffusion	High agreement	94.9% (112/118)
% Agreement of MSSA vs. Cefoxitin Disk Diffusion	High agreement	98% (200/204)
% Agreement of MRSA vs. PBP2' Latex Agglutination	High agreement	93.5% (115/123)
% Agreement of MSSA vs. PBP2' Latex Agglutination	High agreement	98.5% (198/201)
% Agreement of MRSA vs. PCR (mecA)	High agreement	95.7% (111/116)
% Agreement of MSSA vs. PCR (mecA)	High agreement	97% (196/202)

Study Details:

Sample sizes used for the test set and the data provenance:
- Clinical Studies (Primary Test Set): 1,974 compliant nares surveillance specimens.
- Clinical Studies (Sub-analysis for susceptibility comparison): 325 specimens for comparison with Oxacillin MIC and Oxacillin Screen Agar (comprising 117 MRSA and 208 MSSA for MIC, and 116 MRSA and 209 MSSA for Screen Agar).
- Clinical Studies (Comparison to other methods): Sample sizes for MRSA (118 for Cefoxitin Disk, 123 for PBP2', 116 for PCR) and MSSA (204 for Cefoxitin Disk, 201 for PBP2', 202 for PCR) were used.
- Analytical Studies (Reproducibility): 17 test strains.
- Analytical Studies (Expression of Resistance): 17 strains (11 heterogeneous, 5 homogeneous, 1 negative).
- Clinical Reproducibility Testing: 10 S. aureus (MSSA and MRSA) strains.
- Challenge Strain Testing: 20 S. aureus (MSSA and MRSA) strains.
Data Provenance: The clinical studies were conducted at "four geographically diverse clinical sites, composed of regional hospitals and university-based laboratories." This suggests a prospective collection from potentially different regions within the country (likely the US given the FDA submission). Both patient and healthcare worker specimens were included.
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 exact number or qualifications of experts (e.g., medical technologists, clinical microbiologists) involved in establishing the ground truth for the clinical specimens or analytical studies. The ground truth methods used were primarily laboratory-based gold standards (Oxacillin MIC, Oxacillin Screen Agar, PBP2' Latex Agglutination, Cefoxitin Disk Diffusion, PCR for mecA gene, and traditional culture on TSA) which inherently involve trained personnel interpreting results. However, there's no mention of a specific expert consensus panel for establishing the "truth" of each clinical specimen in the way typically seen in image-based diagnostic studies.
Adjudication method for the test set:
Not applicable in the direct sense of human reader disagreement for diagnostic interpretation. The methods establishing ground truth (e.g., Oxacillin MIC, PCR) are objective laboratory tests. For the CMRSA itself, the differentiation of MRSA colonies was based initially on "mauve-colored colonies" and then "specificity was improved by confirming mauve colonies from CMRSA with morphology determination and coagulase testing." This suggests a two-step interpretation process, with a confirmatory test.
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:
Not applicable. This is a study for a culture medium (a laboratory diagnostic device), not an Artificial Intelligence (AI) device or an imaging study involving human readers. Therefore, an MRMC study or assessment of AI assistance is not relevant to this submission.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
This device is a culture medium. Its performance is inherent to the medium itself (i.e., how it differentially grows and colors colonies) and its interpretation is done by trained laboratory personnel. The "standalone" performance is effectively the inherent performance of the medium within the described laboratory workflow. The document describes the raw performance of the medium in detecting MRSA without external human modification of the primary test result. The "colony color alone" results were presented, followed by improved specificity with confirmatory testing, indicating the primary interpretation of the medium.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth was established using a combination of recognized laboratory gold standard methods for MRSA detection:
- Oxacillin MIC (Minimum Inhibitory Concentration): A standard method for determining antimicrobial resistance.
- Oxacillin Screen Agar: A predicate device used for determining Staphylococcus aureus resistance to oxacillin.
- PBP2' Latex Agglutination: A test that detects the penicillin-binding protein 2a, which mediates methicillin resistance.
- Cefoxitin Disk Diffusion: A standard antimicrobial susceptibility test using cefoxitin as a surrogate marker for methicillin resistance.
- PCR detection of the mecA gene: The molecular gold standard for detecting the gene responsible for methicillin resistance in staphylococci.
- Isolation on TSA II/TSA (Tryptic Soy Agar): Non-selective media used for organism isolation, followed by identification and susceptibility testing.
- Confirmatory Coagulase Test: A biochemical test to confirm S. aureus species.
The sample size for the training set:
The document does not explicitly delineate a "training set" in the context of machine learning or AI models. Given that this is a culture medium, the development process would involve extensive laboratory strains (likely hundreds or more during research and development phases not detailed in the 510(k) summary) to optimize the chromogenic formulation, selective agents, and concentrations. The "17 test strains" for reproducibility and "17 strains" for expression of resistance in the analytical studies are part of the validation/verification rather than a machine learning training set. The "panel of twenty (20) challenge strains" in clinical studies are also for validation.
How the ground truth for the training set was established:
As there is no explicit "training set" in the sense of a machine learning model, this question is not directly applicable. For the development and optimization of the culture medium, the ground truth for candidate strains would have been established using established microbiological techniques (e.g., biochemical tests, traditional culture, and antimicrobial susceptibility testing with reference methods like MIC) to confirm their identity (e.g., S. aureus) and their methicillin resistance status.

Summary

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K042812

NOV 2 2 2004

510(k) SUMMARY

SUBMITTED BY:	BECTON, DICKINSON AND COMPANY7 LOVETON CIRCLESPARKS, MD 21152Phone: 410-316-4619Fax: 410-316-4499
CONTACT NAME:	Dennis Mertz, Sr. Manager Regulatory Affairs
DATE PREPARED:	October 8, 2004
DEVICE TRADE NAME:	CHROMagar TM MRSA
DEVICE COMMON NAME:	Culture Medium
DEVICE CLASSIFICATION:	21 CFR§866.1700, Class II
PREDICATE DEVICES:	BBL TM Oxacillin Screen Agar(K863821)

INTENDED USE:

DEVICE DESCRIPTION:

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The incorporation of chromogens and cephalosporin permits the differentiation of MRSA from other organisms.

DEVICE COMPARISON:

The BBL CHROMagar MRSA was compared to BBL Oxacillin Screen Agar (K863821), a legally marketed device to determine resistance of Staphylococcus aureus to oxacillin, methicillin and nafcillin. Since BBL CHROMagar MRSA is designed as a primary plating medium, the most notable differences are the added selectivity, use of cefoxitin as an indicator of methicillin resistance and the inclusion of chromogenic substrates.

The BBL CHROMagar MRSA medium differs from the BBL Oxacillin Screen Aqar method in that:

The BBL CHROMagar MRSA medium is an antimicrobial susceptibility . test medium that is selective and differential while the BBL. Oxacillin Screen Agar is an antimicrobial susceptibility test medium that requires a pure culture prior to inoculation
The BBL CHROMagar MRSA provides detection and identification of . methicillin resistant Staphylococcus aureus (MRSA) at 24 hours and up to 48 hours if necessary. The BBL Oxacillin Screen Agar provides identification at 24 hours.
The BBL CHROMagar MRSA utilizes a specimen swab directly inoculate u to the plate for streaking. BBL Oxacillin Screen Agar requires sample preparation of a pure culture to a 0.5 McFarland standard in TSB prior to plating and streaking.
The BBL CHROMagar MRSA utilizes chromogenic substrates to facilitate . the differentation of Staphylococcus aureus from other bacteria by producing mauve colored colonies. Bacteria other than MRSA appear as blue to blue/green colored colonies. BBL Oxacillin Screen Agar does not differentiate growth on the plate since only pure cultures are used.
The BBL CHROMagar MRSA utilizes cefoxitin as its selective agent. The . BBL™ Oxacillin Screen Agar utilizes oxacillin as its selective agent.
The BBL CHROMagar MRSA uses an incubation temperature of 35 피 37ºC. The BBL Oxacillin Screen Agar utilizes an incubation temperature of 30 - 35℃.

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Screen Agar:
	BBL CHROMagar MRSA	BBL Oxacillin Screen Agar
Intended Use	BBLTM CHROMagarTM MRSA is a selective anddifferential medium for the qualitative direct detection ofnasal colonization by methicillin resistant Staphylococcusaureus (MRSA) to aid in the prevention and control ofMRSA infections in healthcare settings. The test isperformed on anterior nares swab specimens from patientsand healthcare workers to screen for MRSA colonization.BBLTM CHROMagarTM MRSA is not intended todiagnose MRSA infection nor to guide or monitortreatment for infections.	Oxacillin Screen Agar is a antimicrobial susceptibility test medium todetermine resistance of Staphylococcus aureus to oxacillin,methicillin and naficillin.
Specimen type	Anterior nares	Pure culture isolate
Inoculation	Direct from specimen collection device.	Dilution of pure culture from TSA.
Incubation Temperature	Incubation at 35 - 37°C.	Incubation at 30 - 35°C.
Incubation Length	24 hours, if negative re-incubate additional 24 hours.	24 hours.
Selective agent	Cefoxitin 6.0 mg	Oxacillin 6.0 mg
Testing Method	Manual	Manual
Growth Detection	Identification at 24 hours or 48 hours.	Identification at 24 hours.
Organism Differentiation	Chromogenic substrates facilitate differentiation of S. aureus from other organisms.	None
Shelf Life	10 weeks	12 weeks

The following is a table showing the comparison of device characteristics of BBL CHROMagar MRSA to BBL Oxacilling
Screen Agar:

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CHROMagar MRSA	G/L	Oxacillin Screen Agar	G/L
Chromopeptone	40.0	Beef Extract	2.0
Agar	14.0	Agar	17.0
Chromogen Mix	0.5	Starch	1.5
Inhibitory agents	0.07	Acid Hydrolysate ofCasein	9.0
Sodium Chloride	25.0	Sodium Chloride	40.0
Cefoxitin	0.006	Oxacillin	0.006

Ingredients Approximate formula Per liter

SUMMARY OF PERFORMANCE DATA:

ANALYTICAL STUDIES:

Interfering Substances

To determine the effect of potential interfering substances on the recovery and color production of MRSA, a variety of substances expected to be associated with the target specimen were tested with the BBL CHROMagar MRSA (CMRSA). Identification was not adversely affected by commonly used medications, bacterial transport devices, and human blood. A concentration of 10% Phenylephrine Hydrochloride (nasal spray) did show an inhibitory affect on organism growth on both the nonselective blood agar plate (TSA II w/5% sheep blood) and CMRSA.

Reproducibility

Reproducibility testing of the CMRSA was evaluated using 17 test strains. Three different lots of CMRSA were tested to determine that CMRSA reliably detects MRSA within lots, and across lots at different time intervals. Acceptance reproducibility rate of ≥95% for both inter-lot and overall testing intervals was achieved.

Expression of Resistance

To assess the ability of CMRSA to detect MRSA strains with varying levels of resistance expression, a total of 17 strains (11 heterogeneous, 5 homogenous and one negative) were tested. CMRSA was compared to nonselective TSA II w/5% sheep blood medium. Testing demonstrated that CMRSA medium can adequately detect both heterogeneous as well as homogeneous MRSA.

Performance

Determine the performance (sensitivity and specificity) of CMRSA medium, BBL Oxacillin Screen Agar oxacillin MIC and oxacillin and cefoxitin disk diffusion and PBP2 for detection of methicillin resistant S. aureus. The sensitivity and specificity criteria of ≥90% was met for CMRSA as compared to Oxacillin MIC testing and Oxacillin Screen Agar testing however 48 hour incubation is necessary.

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CLINICAL STUDIES:

The CMRSA medium was evaluated at four geographically diverse clinical sites, composed of regional hospitals and university-based laboratories.

Reproducibility Testing

The reproducibility of the CMRSA was evaluated at three clinical sites using a total of 10 methcillin-susceptible (MSSA) and methicillin-resistant (MRSA) S. aureus strains. Observed results were compared to expected results. Overall reproducibility was 100% across all three sites.

Challenge Strain Testing

The performance of the CMRSA was evaluated at three clinical sites using a panel of twenty (20) challenge strains, composed of methcillin-susceptible (MSSA) and methicillin-resistant (MRSA) S. aureus strains. CMRSA was able to reliably detect both at 100%, both at each individual site and across all three sites.

Reference Oxacillin MIC Testing

CMRSA overall recovery of MRSA from 1,974 compliant nares surveillance specimens was at 95% (126/132) when compared to isolation on TSA II of 89% (117/132). As an overall MRSA screening test, % negative agreement was at 99% (1829/1842),when colony color alone was used to report MRSA at 24 hours, and with a confirmatory coagulase test at 48 hours. Specificity was improved by confirming mauve colonies from CMRSA with morphology determination and coagulase testing, particularly at the 48 hour reading, when there was significant breakthrough of mauve-colored coagulase negative staphylococci and gram positive rods. In direct comparison of susceptibility results to Oxacillin MIC, the combined final CMRSA % agreement of MRSA was at 95% (111/117) and % agreement of MSSA was 97% (201/208). Overall category agreement of the CMRSA test with Oxacillin MIC was 96% (312/325).

Reference Oxacillin Screen Agar Testing

CMRSA overall recovery of MRSA from 1,974 nares surveillance specimens was at 95% (125/131) when compared to isolation on TSA of 89% (116/131). As an overall MRSA-screening test, % negative agreement was at 99% (1830/1843), when colony color alone was used to report MRSA at 24 hours, and with a confirmatory coagulase test at 48 hours. Specificity was improved by confirming mauve colonies from CMRSA with morphology determination and coagnlase testing, particularly at the 48 hour reading. In direct comparison of susceptibility results to Oxacillin Screen Agar, the combined final CMRSA % agreement of

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MRSA was acceptable at 95% (110/116), and % agreement of MSSA was 97% (202/209). Overall category agreement of the CMRSA test with Oxacillin Screen Agar was 96% (312/325).

Performance Compared to PBP2' Latex Agglutination, Cefoxitin Disk Diffusion and PCR detection of the mecA gene

CMRSA was also compared to other test methods for identifying MRSA: the PBP2', a Cefoxitin (30µg) disk diffusion test, and PCR detection of the mecA gene. Sensitivity and specificity compared to these additional method is shown in the following table:

CMRSA vs. Cefoxitin Disk Diffusion		CMRSA vs. PBP2' Latex Agglutination		CMRSA vs. PCR (mecA)
% Agreement ofMRSA(95% CI)	% Agreement ofMSSA(95% CI)	% Agreement ofMRSA(95% CI)	% Agreement ofMSSA(95% CI)	% Agreementof MRSA(95% CI)	% Agreementof MSSA(95% CI)
94.9%(112/118)(89.3%,98.1%)	98%(200/204)(95.1%,99.5%)	93.5%(115/123)(87.6%,97.2%)	98.5%(198/201)(95.7%,99.7%)	95.7%(111/116)(90.2%,98.6%)	97%(196/202)(93.6%,98.9%)

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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the circumference. Inside the circle is an abstract symbol that resembles a stylized caduceus or a representation of human figures.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 2 2 2004

Mr. Dennis Mertz Sr. Manager Regulatory Affairs BD Diagnostic Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152

Re: K042812

Trade/Device Name: BBLTM CHROMagar™ MRSA Regulation Number: 21 CFR 866.1700 Regulation Name: Culture Medium for Antimicrobial Susceptibility Tests Regulatory Class: Class II Product Code: JSO Dated: October 8, 2004 Received: October 12, 2004

Dear Mr. Mertz:

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. Iisting 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 (OS) regulation (21 CFR Part 820).

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Page 2

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 (301) 594-3084. 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/dsma/dsmamain.html.

Sincerely yours,

Sallarty

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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Page 1 of 1

510(k) Number: K042812

Device Name: BBLTM CHROMagar™ MRSA

Indications for Use:

BBL™ CHROMagar™ MRSA is a selective and differential medium for the qualitative direct detection of nasal colonization by methicillin resistant Staphylococcus aureus (MRSA) to aid in the prevention and control of MRSA infections in healthcare settings. The test is performed on anterior nares swab specimens from patients and healthcare workers to screen for MRSA colonization. BBLTM CHROMagar™ MRSA is not intended to diagnose MRSA infection nor to guide or monitor treatment for infections.

Prescription Use V (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 In Vitro Diagnostic Devices (OIVD)

fuddie Lu, Rolo

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) <04212

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).