The BD MAX™ MRSA Assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection of Methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of MRSA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The assay also includes a Sample Processing Control (SPC). The Sample Processing Control is present in the Extraction Tube and undergoes the extraction and amplification steps to monitor for inhibitory substances as well as process inefficiency due to instrument or reagent failure. No operator intervention is necessary once the clinical sample and reagent strip are loaded into the BD MAX™ System. The BD MAX™ System automates sample lysis, DNA extraction and concentration, reagent rehydration, nucleic acid amplification and detection of the target nucleic acid sequence using real-time polymerase chain reaction (PCR). Amplified targets are detected with hydrolysis probes labeled with quenched fluorophores. The amplification, detection and interpretation of the signals are done automatically by the BD MAX™ System.

The BD MAX™ System uses a combination of lytic and extraction reagents to perform cell lysis and DNA extraction. Following enzymatic cell lysis at elevated temperature, the released nucleic acids are captured by magnetic affinity beads. The beads with the bound nucleic acids are washed and the nucleic acids are eluted by heat in Elution Buffer. Eluted DNA is neutralized with Neutralization Buffer and transferred to the Master Mix Tube to rehydrate PCR reagents. The reconstituted amplification reagent is dispensed into the BD MAX™ PCR Cartridge. Microvalves in the BD MAX™ PCR Cartridge are sealed by the system prior to initiating PCR to prevent evaporation and amplicon contamination.

The amplified DNA targets are detected using hydrolysis (TagMan®) probes labeled at one end with a fluorescent reporter dye (fluorophore) and at the other end with a quencher moiety. Probes labeled with different fluorophores are used to detect MRSA and SPC amplicons in two different optical channels of the BD MAX™ System: MRSA amplicons are detected in the FAM channel and SPC amplicons are detected in the ROX channel. When the probes are in their native state, the fluorescence of the fluorophore is quenched due to its proximity to the quencher. However, in the presence of target DNA, the probes hybridize to their complementary sequences and are hydrolyzed by the 5'-3' exonuclease activity of the DNA polymerase as it synthesizes the nascent strand along the DNA template. As a result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The amount of fluorescence detected in the two optical channels used for the BD MAX™ MRSA Assay is directly proportional to the quantity of the corresponding probe that is hydrolyzed. The BD MAX™ System measures these signals at the end of each amplification cycle, and interprets the data to provide a result.

AI/ML Overview

1. Acceptance Criteria and Device Performance:

The acceptance criteria are not explicitly stated as numerical thresholds in the provided document. However, the study aims to demonstrate substantial equivalence to the predicate device (BD GeneOhm™ MRSA ACP Assay) based on the presented sensitivity and specificity values. Therefore, the device's performance metrics serve as the "reported device performance" against an implied standard of clinical utility and equivalence.

Metric	Reported Device Performance (BD MAX™ MRSA Assay)	Implied Acceptance Criteria (Based on Substantial Equivalence)
Overall Sensitivity	93.0% (146/157) (87.9%, 96.0% CI)	High sensitivity to detect MRSA, comparable to predicate
Overall Specificity	95.9% (1653/1724) (94.8%, 96.7% CI)	High specificity to correctly identify absence of MRSA, comparable to predicate
Initial Unresolved Rates	0.5% (10/1884) (0.3%, 1.0% CI)	Low unresolved rate
Unresolved Rates After Repeat	0.0% (0/1882) (0.0%, 0.2% CI)	Very low to zero unresolved rate after repeat testing

2. Sample Size and Data Provenance for the Test Set:

Sample Size:
- Clinical Performance (Reference Method): 1903 specimens were reference method compliant (Table 2, footnote 3).
- Comparison to Direct Culture: 1881 specimens (Table 3).
- Unresolved Rates: 1884 specimens were PCR method compliant for initial rates, and 1882 for rates after repeat (Table 5, footnote 2).
Data Provenance:
- Country of Origin: Not explicitly stated, but the submission is from GeneOhm Sciences Canada Inc. (BD Diagnostics) and the FDA approval is from the US. The study involved "multi-site prospective investigational study" with "Four (4) investigational centers participated," suggesting US or North American data.
- Retrospective or Prospective: Prospective. The document states: "Clinical performance characteristics of the BD MAX™ MRSA Assay were determined in a multi-site prospective investigational study."

3. Number of Experts and Qualifications for Ground Truth:

The document does not mention the use of human experts to establish the ground truth in the traditional sense of consensus reading for diagnostic imaging or clinical assessment.

Ground Truth Method: The "Comparative Reference Method" used a laboratory-based process: direct culture complemented by enriched culture. The identification of S. aureus was confirmed with an agglutination test, and Methicillin-resistance was confirmed by Cefoxitin disk diffusion susceptibility testing. No human experts are described as providing subjective interpretations for ground truth.

4. Adjudication Method for the Test Set:

Not applicable. The ground truth was established through objective laboratory culture and susceptibility testing, not through expert consensus or a process that would require adjudication.

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

No, an MRMC comparative effectiveness study was not done. This device is an automated, in vitro diagnostic molecular assay (PCR-based), not an imaging or clinical interpretation tool that relies on human readers. Therefore, the concept of human readers improving with or without AI assistance does not apply in this context.

6. Standalone Performance Study:

Yes, a standalone study was performed. The entire clinical performance section (Tables 1-5) details the performance of the BD MAX™ MRSA Assay (the algorithm/device only) compared to a defined reference method. This is a direct measure of the algorithm's performance without human intervention in result interpretation. The "amplification, detection and interpretation of the signals are done automatically by the BD MAX™ System."

7. Type of Ground Truth Used:

Laboratory Reference Method: The ground truth was established using a "Comparative Reference Method" which consisted of direct culture complemented by enriched culture. This involved:
- Presumptive S. aureus colonies on selective media.
- Subculture onto Blood Agar (BA).
- Identification confirmed with an agglutination test.
- Methicillin-resistance confirmed by Cefoxitin disk (30μg) diffusion susceptibility testing.
- Enrichment in Trypticase Soy Broth with 6.5% NaCl (TSB 6.5% NaCl) for initial direct culture-negative specimens, followed by re-inoculation and MRSA confirmation as above.

8. Sample Size for the Training Set:

The document does not provide information on the sample size used for the training set. This submission focuses on the performance of the final device in a clinical validation study rather than the development process.

9. How Ground Truth for the Training Set Was Established:

The document does not provide information on how the ground truth for the training set was established. As mentioned above, the focus is on the validation study, not the development data.

Summary

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5 2012 JUL

June 1, 2012

510(K) SUMMARY

BD MAX™ MRSA Assay

Submitted by:

GeneOhm Sciences Canada Inc. (BD Diagnostics) 2555, Boul. du Parc-Technologique Québec (Québec) Canada G1P 4S5

Contact:

Patricia Dionne, Ph.D.

Name of Device:

Trade Name: Common Name: Classification Name: BD MAX™ MRSA Assay MRSA detection assay System, Test, Genotypic Detection, resistant and nonresistant markers, Staphylococcus colonies

Predicate Device:

Performance/ Technology

BD GeneOhm™ MRSA ACP Assay (K093346)

Device Description:

Intended Use:

Test Description:

A nasal specimen is collected and transported to the laboratory using the recommended swab. The swab is placed in a BD MAX™ MRSA Sample Buffer Tube. The Sample Buffer Tube is vortexed to release cells from the swab into the buffer. The Sample Buffer Tube is placed onto the BD MAX™ System and the following automated procedures occur: the bacterial cells are lysed, DNA is extracted on magnetic beads and concentrated, then an aliquot of the eluted DNA is added to PCR reagents which contain the MRSA-specific primers used to amplify the genetic target, if present. The assay also

BD Diagnostics BD MAX™ MRSA Assay 510(k) Summary

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includes a Sample Processing Control (SPC). The Sample Processing Control is present in the Extraction Tube and undergoes the extraction and amplification steps to monitor for inhibitory substances as well as process inefficiency due to instrument or reagent failure. No operator intervention is necessary once the clinical sample and reagent strip are loaded into the BD MAX™ System. The BD MAX™ System automates sample Ivsis. DNA extraction and concentration. reagent rehydration, nucleic acid amplification and detection of the target nucleic acid sequence using real-time polymerase chain reaction (PCR). Amplified targets are detected with hydrolysis probes labeled with quenched fluorophores. The amplification, detection and interpretation of the signals are done automatically by the BD MAX™ System.

The BD MAX™ System uses a combination of lytic and extraction reagents to perform cell lysis and DNA extraction. Following enzymatic cell lysis at elevated temperature, the released nucleic acids are captured by maqnetic affinity beads. The beads with the bound nucleic acids are washed and the nucleic acids are eluted by heat in Elution Buffer. Eluted DNA is neutralized with Neutralization Buffer and transferred to the Master Mix Tube to rehvdrate PCR reagents. The reconstituted amplification reagent is dispensed into the BD MAX™ PCR Cartridge. Microvalves in the BD MAX™ PCR Cartridge are sealed by the system prior to initiating PCR to prevent evaporation and amplicon contamination.

Substantial Equivalence:

The BD MAX™ MRSA Assay is substantially equivalent in performance to the BD GeneOhm™ MRSA ACP Assay (K093346).

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Performance data:

Clinical performance characteristics of the BD MAX™ MRSA Assay were determined in a multi-site prospective investigational study. Four (4) investigational centers participated in the study.

The Comparative Reference Method consisted of direct culture complemented by enriched culture. Enriched culture analysis was completed for all specimens that were negative for MRSA by direct culture. Presumptive S. aureus colonies observed on. selective (S. aureus) chromogenic media were subcultured onto Blood Agar (BA). Identification was confirmed with an agglutination test, while Methicillin-resistance was confirmed by Cefoxitin disk (30μg) diffusion susceptibility testing. Enrichment in Trypticase Soy Broth with 6.5% NaCl (TSB 6.5% NaCl) was completed in the event that Methicillin-resistant S. aureus was not confirmed by the initial direct culture method. Turbid TSB 6.5% NaCl broth was used to inoculate additional chromogenic media and BA plates; MRSA confirmation was performed as described above.

Results obtained are summarized in Tables 1 to 5.

Table 1: Results Obtained with the BD MAX™ MRSA Assay in Comparison to the Reference Method

... 25 . 15	4W .	CHICH17 100
AND SELL.1 25 4 5 = 1 = 1 =------------------------------------------------------------------------------------------------------------------------------------------------------------------------------11 13 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8FILL 11 11 23 21 11 112019A112 111 11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1.* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *. "11525652575.3-51 6132 111 .1 1 = 1 = 9 = 4 = 4 = 4 = = = = =. STARROMASTE.11 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 114 19 11 1 1 1 1 1 1 1 1 1 1STAYALL I.	...· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·	--------------------------------------	AT REE E E REAM BERRE

BD MAX™ MRSA /
In the first of the support of the state of the states			11

1The total number of specimens that were reference and PCR method compliant

Table 2: Performance Obtained using the BD MAX™ MRSA Assay in Comparison to the Reference Method

Clinical Sites	Prevalence¹	Sensitivitywith 95% CI²	Specificitywith 95% CI²
Site 1	5.6% (28/496)	100.0% (28/28)(87.9%, 100.0%)	95.8% (435/454)(93.6%, 97.3%)
Site 2	4.6% (23/505)	91.3% (21/23)(73.2%, 97.6%)	96.5% (465/482)(94.4%, 97.8%)
Site 3	13.2% (55/417)	90.9% (50/55)(80.4%, 96.1%)	95.8% (346/361)(93.3%, 97.5%)
Site 4	10.9% (53/485)	92.2% (47/51)(81.5%, 96.9%)	95.3% (407/427)(92.9%, 96.9%)
Overall³	8.4% (159/1903)	93.0% (146/157)(87.9%, 96.0%)	95.9% (1653/1724)(94.8%, 96.7%)

Prevalence based on reference method only

CI: Confidence Intervals

3 1903 specimens were reference method compliant

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Table 3: Results Obtained with the BD MAX™ MRSA Assay in Comparison to Direct Culture

	All Sites	Direct Culture
		+	-	Total
BD MAX™ MRSA Assay	+	133	84	217
BD MAX™ MRSA Assay	-	7	1657	1664
	Total	140	1741	1881

Table 4: Performance Obtained using the BD MAX™ MRSA Assay in Comparison to Direct Culture

Clinical Sites	Positive Agreementwith 95% CI¹	Negative Agreementwith 95% CI¹
Site 1	100.0% (22/22)(85.1%, 100.0%)	94.6% (435/460)(92.1%, 96.3%)
Site 2	95.5% (21/22)(78.2%, 99.2%)	96.5% (466/483)(94.4%, 97.8%)
Site 3	94.1% (48/51)(84.1%, 98.0%)	95.3% (348/365)(92.7%, 97.1%)
Site 4	93.3% (42/45)(82.1%, 97.7%)	94.2% (408/433)(91.6%, 96.1%)
Overall	95.0% (133/140)(90.0%, 97.6%)	95.2% (1657/1741)(94.1%, 96.1%)

' CI: Confidence Intervals

Table 5: Unresolved Rates

Clinical Sites	Initial Unresolved Rateswith 95% CI1		Unresolved Rates After Repeatwith 95% CI1
Site 1	0.8% (4/484)	(0.3%, 2.1%)	0.0% (0/483)	(0.0%, 0.8%)
Site 2	0.0% (0/505)	(0.0%, 0.8%)	0.0% (0/505)	(0.0%, 0.8%)
Site 3	0.2% (1/416)	(0.0%, 1.3%)	0.0% (0/416)	(0.0%, 0.9%)
Site 4	1.0% (5/479)	(0.4%, 2.4%)	0.0% (0/478)	(0.0%, 0.8%)
Overall	0.5% (10/1884)2	(0.3%, 1.0%)	0.0% (0/1882)	(0.0%, 0.2%)

° CI: Confidence Intervals

² 1884 specimens were PCR method compliant

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name arranged in a circular pattern around the perimeter. At the center is a stylized emblem of an eagle, which is a common symbol used in US government seals.

Public Health Service

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

BD Diagnostics, Inc c/o Mr. Raymond J. Boulé Director, Regulatory Affairs 7 Loveton Circle, Mail Code 614 Sparks, MD 21152

5 2012 JUL

Re: K120138

Trade/Device Name: BD MAXTM MRSA Assay Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: Class II Product Code: NQX, OOI Dated: June 15, 2012 Received: June 18, 2012

Dear Mr. Boulé:

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 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of

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Page 2 - Mr. Raymond J. Boulé

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 (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

SagaAya

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

Enclosure

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Indications for Use Statement

510(k) Number (if known): K120138

Device Name: _________________________________________________________________________________________________________________________________________________________________

Indication(s) for Use:

Intended Use

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (per 21 CFR §801, Subpart D) OR

Over-The-Counter Use (per 21 CFR §801, Subpart C) [Optional Format 01/02/1996]

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices Evaluation and Safety (OIVD)

Fredda M. Poole

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

510(k): K120138

Regulation Number and Section

§ 866.1640 Antimicrobial susceptibility test powder.

(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).