BBL™ CHROMagar™ MRSA II is a selective and differential chromogenic 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 to screen for MRSA colonization.

BBL CHROMagar MRSA II is not intended to diagnose, guide or monitor treatment for MRSA infections. A negative result does not preclude MRSA nasal colonization. Concomitant cultures are necessary for organism identification, susceptibility testing or epidemiological typing.

Device Description

BBL™ CHROMagar™ MRSA II (CMRSA II) permits the direct detection and identification of MRSA through the incorporation of specific chromogenic substrates and cefoxitin. MRSA strains will grow in the presence of cefoxitin' and produce mauvecolored colonies resulting from hydrolysis of the chromogenic substrate. Selective agents are incorporated for the suppression of gram-negative organisms, yeast and enterococci and some other gram-positive cocci. Bacteria other than MRSA may utilize other chromogenic substrates in the medium resulting in the growth of colonies that are not mauve.

AI/ML Overview

Here is an analysis of the provided text regarding the BBL™ CHROMagar™ MRSA II device:

Acceptance Criteria and Device Performance

The provided document describes the BBL™ CHROMagar™ MRSA II and its performance in detection of MRSA. The acceptance criteria and reported device performance are primarily presented in terms of Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to established reference methods.

Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied/Reference)	Reported Device Performance (BBL™ CHROMagar™ MRSA II)	Notes
Reproducibility	>95% for inter-lot and overall testing intervals	100% (Individual and combined site reproducibility agreements across three successive days for 10 masked S. aureus strains)	Analytical studies also showed >95% for both inter-lot and overall testing intervals for 20 test strains.
PPA vs. Cefoxitin Disk	Not explicitly stated, but typically high agreement is expected for diagnostic devices.	92% (149/162) (95% CI: 86.7%, 95.7%)	Used as a primary reference method for MRSA status, particularly for the 13 discrepant samples from the Traditional Culture comparison.
NPA vs. Cefoxitin Disk	Not explicitly stated, but typically high agreement is expected for diagnostic devices.	99.9% (1024/1025) (95% CI: 99.5%, 100%)	Used as a primary reference method for MRSA status.
PPA vs. Traditional Culture (Combined Sites)	Not explicitly stated, but typically high agreement is expected for diagnostic devices.	92% (92/100) (95% CI: 84.8%, 96.5%)	This includes 9 samples that were positive on CMRSA II and negative by Traditional Culture, but were subsequently confirmed as MRSA by cefoxitin disk diffusion. This suggests the Traditional Culture might have missed some true positives.
NPA vs. Traditional Culture (Combined Sites)	Not explicitly stated, but typically high agreement is expected for diagnostic devices.	98.8% (760/769) (95% CI: 97.8%, 99.5%)
PPA vs. Traditional Culture (Third Site)	Not explicitly stated, but typically high agreement is expected for diagnostic devices.	90.2% (46/51) (95% CI: 78.6%, 96.7%)	This includes 2 samples that were positive on CMRSA II and negative by Traditional Culture, but were subsequently confirmed as MRSA by cefoxitin disk diffusion.
NPA vs. Traditional Culture (Third Site)	Not explicitly stated, but typically high agreement is expected for diagnostic devices.	98.9% (264/267) (95% CI: 96.8%, 99.8%)

Study Details

2. Sample size used for the test set and the data provenance

Clinical Accuracy Test Set Size: A total of 1187 compliant remnant, prospective, naive specimens.
Data Provenance: The study was conducted at three diverse clinical laboratories in the U.S. The data is prospective, as it was collected from "remnant, prospective, nares specimens."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The document does not specify the number of experts used in establishing the ground truth, nor does it detail their qualifications. The ground truth was based on laboratory methods (cefoxitin disk diffusion and traditional culture), which would have been performed and interpreted by trained laboratory personnel, but not necessarily "experts" in the sense of clinicians or radiologists.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The document does not explicitly describe an adjudication method for the test set in the conventional sense of multiple human readers reviewing results. Instead, any discrepancies between the BBL™ CHROMagar™ MRSA II and the Traditional Culture were reconciled by referring to the cefoxitin disk diffusion test method as the definitive reference. For example, 9 samples from the combined sites and 2 samples from the third site that were positive on CMRSA II but negative by Traditional Culture were confirmed as MRSA by cefoxitin disk diffusion.

5. 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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study focuses on the performance of a culture medium device (BBL™ CHROMagar™ MRSA II), not an AI algorithm or an assistance tool for human readers. Therefore, there is no information on human reader improvement with or without AI assistance.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This is a standalone performance evaluation of a culture medium, not an algorithm. The device itself (BBL™ CHROMagar™ MRSA II) performs the detection based on phenotypic characteristics (mauve colonies and growth in cefoxitin). The interpretation of positive or negative (presence of mauve colonies) is done by laboratory personnel directly observing the plate, which could be considered a "human-in-the-loop" step, but the core analytical performance is derived from the medium itself reacting to the bacteria. However, it's not an "algorithm-only" or "AI" study in the typical sense.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the clinical accuracy study was primarily based on:

Cefoxitin Disk Diffusion Test Method: This is a standard laboratory method for determining methicillin resistance in Staphylococcus aureus.
Traditional Culture Media: This served as a comparative method.
Adjudication by Cefoxitin Disk: For discrepancies between the BBL™ CHROMagar™ MRSA II and Traditional Culture, the cefoxitin disk diffusion test was used to confirm MRSA status.

This combination of laboratory-based tests represents the "gold standard" or reference method for determining the presence and methicillin resistance of S. aureus in clinical samples.

8. The sample size for the training set

The document does not mention a "training set" in the context of machine learning or AI. Rather, it refers to:

Analytical Studies: Used 20 test strains for reproducibility, and 7 test strains for Limit of Detection (LOD) and analytical reactivity. A suspension of 1x10^5 CFU/mL was used for these studies.
Challenge Strain Testing: Involved 20 challenge strains of S. aureus (14 MRSA, 6 MSSA).
Reproducibility Testing (Clinical): Involved 10 masked strains of S. aureus (7 MRSA, 3 MSSA).

These "strains" or "test strains" function as internal controls and known samples to establish the device's inherent analytical capabilities, similar to a "development" or "validation" set for the device's formulation, but not a "training set" for an algorithm.

9. How the ground truth for the training set was established

As there is no "training set" in the AI sense, there isn't a ground truth established for one. For the analytical and challenge strain testing, the ground truth was inherently known because these were cultured strains with confirmed characteristics (MRSA/MSSA status). The document does not detail the exact methodology for confirming the MRSA status of these "training" or "challenge" strains, but it would have been through standard microbiological methods like those mentioned (e.g., genetic testing or other antimicrobial susceptibility testing to oxacillin/cefoxitin).

Summary

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CONFIDENTIAL AND PROPRIETARY

	510(k) SUMMARY
SUBMITTED BY:	BECTON, DICKINSON AND COMPANY7 LOVETON CIRCLESPARKS, MD 21152Phone: 410-316-4905Fax: 410-316-4499	AUG 20 2010
CONTACT NAME:	Paul Swift, Regulatory Affairs Specialist
DATE PREPARED:	August 12, 2010
DEVICE TRADE NAME:	BBL TM CHROMagar TM MRSA II
DEVICE COMMON NAME:	Culture Medium
DEVICE CLASSIFICATION:	21 CFR§866.1700, Class II
PREDICATE DEVICES:	BBL TM CHROMagar TM MRSA (K042812)BBL TM Oxacillin Screen Agar (K863821)

INTENDED USE:

DEVICE DESCRIPTION:

BD Diagnostic Systems Becton, Dickinson and Company
l

4 Clinical and Laboratory Standards Institute. 2009. Performance Standards for Antimicrobial Susceptibility Testing; Nineteenth Informational Supplement, M100-S19. Clinical and Laboratory Standards Institute, Wayne, PA.

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chromogenic substrates in the medium resulting in the growth of colonies that are not mauve.

DEVICE COMPARISON:

The BBLTM CHROMagar™ MRSA II (CMRSA II) differs from the BBL CHROMagar MRSA (CMRSA) (K042812) in the following ways:

CMRSA II detects and identifies MRSA within 20-26 hours; whereas, CMRSA . detects and identifies MRSA at 24 ± 4 hours to 48 ± 4 hours.

The BBL™ CHROMagar™ MRSA II differs from the BBL™ Oxacillin Screen Agar (OSA) (K863821) in the following ways:

CMRSA II is selective and differential culture medium for antimicrobial . susceptibility testing of MRSA, whereas, OSA is a selective culture medium for antimicrobial susceptibility testing of MRSA.
CMRSA II is intended to identify MRSA from nares specimens; whereas, OSA is . cleared for the identification of MRSA from pure clinical isolates that were identified as Staphylococcus aureus.
CMRSA II utilizes direct inoculation from specimen collection devices. OSA . utilizes indirect inoculation from a broth suspension of pure S. aureus colonies isolated from18-24 hour culture.
. CMRSA II utilizes cefoxitin as a selective agent to differentiate MRSA from methicillin-susceptible S. aureus and other organisms; whereas, OSA utilizes oxacillin as a selective agent to identify MRSA from a pure S. aureus culture.
CMRSA II utilizes chromogenic substances to facilitate the differentiation of . MRSA from MSSA and other organisms; whereas, OSA does not contain chromogenic substances to differentiate growth on the plate.
CMRSA II produces mauve colonies as an indicator of MRSA; whereas, any . colony growth seen on OSA is an indicator of MRSA.
CMRSA II detects and identifies MRSA in 20-26 hours; whereas, OSA identifies . MRSA in 24 hours.
CMRSA II utilizes incubation conditions at a temperature of 35-37℃; whereas, . OSA utilizes incubation conditions at temperature of 30-35°C.

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SUMMARY OF PERFORMANCE DATA:

Analytical Studies:

Interfering Substances

Commonly used transport devices, nasal spray and whole blood were evaluated for potential interference and inhibition of MRSA on CMRSA II.

Nasal sprays containing fluticasone propionate, azelastine hydrochloride and oxymetazoline hydrochloride as well as OTC throat drops containing menthol demonstrated antibacterial activity. No other substances or transport devices interfered with recovery of MRSA on CMRSA II.

Reproducibilitv

Reproducibility testing of the CMRSA II was evaluated using 20 test strains. Three different lots of CMRSA II were tested to determine that CMRSA II reliably detects MRSA within lots and across lots. Acceptance criteria for reproducibility of >95% for both inter-lot and overall testing intervals was met.

Recovery Rate (Limit of Detection)

BBL CROMagar MRSA II was evaluated to determine the recovery rate (limit of detection (LOD)) for recovery of methicillin-resistant S. aureus. Seven test strains, representing five heterogeneous and two homogeneous MRSA were evaluated for recovery on BBL CHROMagar MRSA II. Non-selective Columbia Agar with 5% Sheep Blood plates were used to determine the organism concentration expressed in colony forming units (CFU) for each dilution. Analytical studies, including incubation time, analytical reactivity or sensitivity, interfering substances and reproducibility were all performed using an MRSA suspension of 1x105 CFU/mL. Ten ul of this suspension was then inoculated on to BBL CHROMagar MRSA II.

Clinical Studies

Reproducibility Testing

Testing of ten (10) masked strains of S. aureus was conducted at three clinical sites. The panel included seven (7) MRSA and three (3) methicillin sensitive S. aureus (MSSA). Individual and combined site reproducibility agreements were 100% across three successive days.

Challenge Strain Testing

Testing of twenty (20) challenge strains of S. aureus was conducted at three clinical sites. The panel included 14 MRSA and 6 MSSA. Individual sites and combined site agreements were 100%.

Clinical Accuracy

The performance of BBL™ CHROMagar™ MRSA II was evaluated at three diverse clinical laboratories in the U.S. A total of 1187 compliant remnant, prospective, nares

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specimens were enrolled. Specimens were evaluated by comparing the recovery of MRSA on traditional culture media and BBLTM CHROMagar™ MRSA II plates. S. aureus recovered on the traditional culture media was tested by the cefoxitin disk diffusion test method. BBL™ CHROMagar™ MRSA II was interpreted as positive for MRSA at 20-26 hours based on detection of mauve colonies.

A total of 162 specimens were found to be MRSA positive. The positive percent agreement of BBLTM CHROMagar™ MRSA II to cefoxitin disk was 92% (149/162). The negative percent agreement of BBL CHROMagar MRSA II compared to cefoxitin disk 99.9% (1024/1025) (Table 1).

Table 1: BBL™ CHROMagar™ MRSA II Performance versus Cefoxitin Disk

	Cefoxitin Disk
CMRSA II Result	MRSA	Not MRSA	Total
MRSA	149	1	150
Not MRSA	13	1024	1037
	162	1025	1187

Reference Method: Cefoxitin Disk Positive Percent Agreement: 92% (86.7%, 95.7%) Negative Percent Agreement: 99.9% (99.5%, 100%)

With combined data from two clinical trial sites, the positive percent agreement of BBL™ CHROMagar™ MRSA II compared to Traditional Culture was 92% at 20-26h and the negative percent agreement was 98.8% (Table 2).

	Table 2: BBL™ CHROMagar™ MRSA II Performance vs. Traditional Culture at
Two Clinical Trial Sites

	Traditional Culture
CMRSA II Result	MRSA	Not MRSA	Total
MRSA	92	9*	101
Not MRSA	8	760	768
	100	769	869

Reference Method: Traditional Culture Positive Percent Agreement: 92% (84.8%, 96.5%) Negative Percent Agreement: 98.8% (97.8%, 99.5%)

Nine samples that were positive on BBL™ CHROMagar™ MRSA II and negative by Traditional Culture were confirmed as MRSA by cefoxitin disk diffusion testing.

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At the third clinical trial site, the positive percent agreement of BBL™ CHROMagar™ MRSA II compared to Traditional Culture was 90.2% at 20-26h and the negative percent agreement was 98.9% (Table 3).

Table 3: BBL™ CHROMagar™ MRSA II Performance vs. Traditional Culture at Third Clinical Trial Site

	Traditional Culture
CMRSA II Result	MRSA	Not MRSA	Total
MRSA	46	3*	49
Not MRSA	5	264	269
	51	267	318

Reference Method: Traditional Culture Positive Percent Agreement: 90.2% (78.6%, 96.7%) Negative Percent Agreement: 98.9% (96.8%, 99.8%)

Two samples that were positive on BBL™ CHROMagar™ MRSA II and negative by Traditional Culture were confirmed as MRSA by cefoxitin disk diffusion testing.

BD Diagnostic Systems Becton, Dickinson and Company

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center-WO66-G609 Silver Spring, MD 20993-0002

Mr. Paul Swift Regulatory Affairs Specialist Becton Dickinson and Company 7 Loveton Circle Sparks, MD 21152

AUG 2 0 2010

Re: K092767

Trade/Device Name: BBL™ CHROMagar™ MRSA II Regulation Number: 21 CFR §866.1700 Regulation Name: Culture Medium for Antimicrobial Susceptibility Tests Regulatory Class: II Product Code: JSO Dated: August 18, 2010 Received: August 19, 2010

Dear Mr. Swift:

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 (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 to!!-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,

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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Indication for Use

K092767

510(k) Number (if known): K092767

Device Name: BBLTM CHROMagar™ MRSA II

Indication For Use:

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Luddi le Roo ly

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

510(k) K692767

BD Diagnostic Systems Becton, Dickinson and Company

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).