The Alere™ PBP2a Test is a qualitative, in vitro immunochromatographic assay for the detection of penicillin-binding protein 2a (PBP2a) in isolates identified as Staphylococcus aureus, as an aid in detecting methicillin-resistant Staphylococcus aureus (MRSA). The Alere™ PBP2a Test is not intended to diagnose MRSA nor to guide or monitor treatment for MRSA infections.

Device Description

The Alere™ PBP2a Test is a rapid immunochromatographic membrane assay that uses highly sensitive monoclonal antibodies to detect the PBP2a protein directly from bacterial isolates. These antibodies and a control antibody are immobilized onto a nitrocellulose membrane as two distinct lines and combined with a sample pad, a blue conjugate pad, and an absorption pad to form a test strip. Isolates are sampled directly from the culture plate and eluted into an assay tube containing Reagent 2 is then added and the dipstick is placed in the assay tube. Results are read visually at 5 minutes.

AI/ML Overview

Acceptance Criteria and Study Details for Alere™ PBP2a Test

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state "acceptance criteria" in a quantitative manner (e.g., "Sensitivity must be >= 95%"). However, the clinical performance study aims to demonstrate substantial equivalence, implying that the observed performance (Sensitivity and Specificity compared to the reference method) was deemed acceptable for market clearance. Based on the "Clinical Performance" section, the performance of the device was evaluated against cefoxitin (30 ug) disk diffusion.

Metric (Implicit Acceptance Criteria)	Device Performance (Tryptic Soy Agar with 5% sheep blood)	Device Performance (Columbia Agar with 5% sheep blood)	Device Performance (Mueller Hinton with 1 µg oxacillin induction)
Sensitivity	98.1% (95% C.I. 95.2-99.3%)	99.0% (95% C.I. 96.6-99.7%)	99.5% (95% C.I. 97.4-99.9%)
Specificity	98.8% (95% C.I. 96.5-99.6%)	98.8% (95% C.I. 96.5-99.6%)	98.8% (95% C.I. 96.5-99.6%)
Reproducibility	97.3% agreement with expected results (580/596) - Overall for all sites	97.3% agreement with expected results (580/596) - Overall for all sites	97.3% agreement with expected results (580/596) - Overall for all sites

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

Sample Size for Test Set: A total of 457 S. aureus samples were evaluated in the clinical performance study.
Data Provenance:
- Country of Origin: The clinical performance study was conducted at "three geographically-diverse laboratories." The document explicitly mentions "a collection of strains from Department of Infectious Disease Epidemiology of the Imperial College in London, England" for the analytical performance (analytical reactivity and specificity), which suggests that at least some data or strains originated from outside the US. The main clinical study likely included US sites given the FDA submission, but this is not explicitly stated.
- Retrospective or Prospective: Not explicitly stated. The wording "A total of 457 S. aureus samples were evaluated" does not indicate whether these were prospectively collected or retrospectively analyzed isolates.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

The document does not specify the number of experts or their qualifications used to establish the ground truth for the test set.

4. Adjudication Method for the Test Set

The document does not specify any adjudication method used for the test set.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. The study compares the device's performance directly to a reference method (cefoxitin disk diffusion), not the performance of human readers with or without AI assistance.

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

Yes, the study describes the standalone (algorithm only) performance of the device. The Alere™ PBP2a Test is a rapid immunochromatographic membrane assay where results are "read visually at 5 minutes." The performance metrics (Sensitivity and Specificity) are for the device's ability to detect PBP2a compared to the reference method. While a human visually reads the result, the performance assessed is of the diagnostic test itself, not a human interpreting images/data that the device produces.

7. The Type of Ground Truth Used

The ground truth used for the clinical performance study was established by cefoxitin (30 ug) disk diffusion, interpreted according to CLSI (Clinical and Laboratory Standards Institute) standards. This is a recognized laboratory method for determining methicillin resistance in Staphylococcus aureus.

8. The Sample Size for the Training Set

The document does not explicitly state a dedicated "training set" size. The "Analytical Reactivity and Specificity" section mentions testing 162 strains of MRSA and 112 strains of MSSA with expected results to demonstrate analytical performance. While these strains might have informed the development of the device, they are presented as part of an analytical validation rather than a distinct "training set" in the context of machine learning model development. The device described (immunochromatographic assay) is not a machine learning algorithm that requires a traditional training set.

9. How the Ground Truth for the Training Set was Established

As mentioned above, there isn't a "training set" in the machine learning sense. For the strains used in analytical testing (162 MRSA and 112 MSSA), the ground truth (whether they were MRSA or MSSA) was established based on their classification from their source (NARSA, ATCC, and Imperial College collection). These are well-characterized strains with established resistance profiles.

Summary

{0}------------------------------------------------

510(K) SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________

JUL 26 2012

SUBMITTER

Alere Scarborough, Inc. 10 Southgate Road Scarborough, ME 04074 Establishment Registration Number: 1221359

CONTACT PERSON

Angela Drysdale (207) 730-5737 (Office) (207) 730-5717 (FAX) Angela.drysdale@alere.com (email)

DATE PREPARED

6/27/2012

TRADE NAME Alere™ PBP2a Test

COMMON NAME Alere™ PBP2a Test, Alere™ PBP2a

CLASSIFICATION NAME

System, Test, Genotypic Detection, Resistant Markers, Staphylococcus Colonies (per 21 CFR 866.1640)

CLASSIFICATION Class II

PRODUCT CODE MYI

PANEL Microbiology

PREDICATE DEVICES Alere™ PBP2a Test, K091766

{1}------------------------------------------------

DEVICE DESCRIPTION

lsolates are sampled directly from the culture plate and eluted into an assay tube containing Reagent 2 is then added and the dipstick is placed in the assay tube. Results are read visually at 5 minutes.

INTENDED USE

The Alere™ PBP2a Test is a qualitative, in vitro immunochromatographic assay for the detection of penicillinbinding protein 2a (PBP2a) in isolates identified as Staphylococus aureus, as an aid in detecting methicillinresistant Staphylococcus aureus (MRSA). The Alere™ PBP2a Test is not intended to diagnose MRSA nor to guide or monitor treatment for MRSA infections.

TECHNOLOGICAL CHARACTERISTICS

The Alere™ PBP2a Test uses lateral flow immunochromatographic technology. The test is a rapid immunoassay that employs specific antibodies immobilized onto a solid phase to detect PBP2a from bacterial isolates.

PERFORMANCE SUMMARY

Clinical Performance

The clinical performance of the Alere™ PBP2a Test was established in a multi-center clinical study conducted in 2009 at three geographically-diverse laboratories.

A total of 457 S. aureus samples were evaluated in the Alere™ PBP2a Test, compared to results of 30 ue cefoxitin disk diffusion and interpreted according to CLSI standards. Performance results by plate type are listed in Table 1 below.

Table 1: Alere™ PBP2a Test Performance Compared to Cefoxitin (30 ug) Disk Diffusion in S. aureus Isolates: Results by Plate Type

Plate Type	Sensitivity	95% C.I.	Specificity	95% C.I.
Tryptic Soy Agarwith 5% sheepblood	98.1%(206/210)	( 95.2-99.3%)	98.8%(244/247)	( 96.5-99.6%)
Columbia Agarwith 5% sheepblood	99.0%(208/210)	( 96.6-99.7%)	98.8%(244/247)	( 96.5-99.6%)
Mueller Hintonwith 1 µg oxacillininduction	99.5%(209/210)	( 97.4-99.9%)	98.8%(244/247)	( 96.5-99.6%)

{2}------------------------------------------------

Analytical Performance

Analytical Reactivity and Specificity

162 strains of methicillin-resistant Staphylococcus aureus (MRSA) and 112 strains of methicillin-sensitive Staphylococus aureus (MSSA) were tested in the Alere™ PBP2a Test with expected results. These bacterial strains were obtained from the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA), American Type Culture Collection (ATCC) and a collection of strains from Department of Infectious Disease Epidemiology of the Imperial College in London, England.

Reproducibility Study

A study of the Alere™ PBP2a Test was conducted at 3 separate sites using panels of blind coded specimens containing negative and positive samples. Participants tested each sample twice on 5 different days. There was 97.3% (580/596) agreement with expected test results.

Signed

Angela Drysdale Director of Clinical Affairs Alere Scarborough, Inc.

Date

{3}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three wing-like shapes, positioned to the right of a circular seal. The seal contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter.

Public Health Service

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

Alere Scarborough, Inc. c/o Angela Drysdale Director of Clinical Affairs 10 Southgate Road Scarborough, ME 04074

JUL 26 2012

Re: K121905 Trade Name: Alere™PBP2a Test Regulation Number: 21 CFR §866.1640 Regulation Name: Antimicrobial susceptibility test powder. Regulatory Class: Class II Product Code: MYI Dated: June 27, 2012 Received: June 29, 2012

Dear Ms. Drysdale:

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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. This letter will allow you to begin marketing your device as described in your Section

{4}------------------------------------------------

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 Part 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,

Jayaat

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

{5}------------------------------------------------

INDICATIONS FOR USE STATEMENT

510(k) Number (if known):

Device Name: Alere™ PBP2a Test

Indications For Use:

K121905

Prescription Use __ X (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 In Vitro Diagnostic Devices (OIVD)

Selyatry

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

510(k) K121905;

Page 1 of _

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).