The Alere™ PBP2a SA Culture Colony Test is a qualitative, in vitro immunochromatographic assay for the rapid detection of penicillin-binding protein 2a (PBP2a) in isolates identified as Staphylococcus aureus as an aid in identifying methicillin-resistant Staphylococcus aureus (MRSA).

Device Description

The Alere™ PBP2a SA Culture Colony Test is a rapid immunochromatographic membrane assay intended for the detection of penicillin-binding protein 2a (PBP2a) in isolates identifies as Staphylococcus aureus as an aid in identification of MRSA. The test uses highly sensitive recombinant monoclonal antibody fragments (rFabs) to detect the PBP2a protein directly from bacterial isolates. The rFab and a control antibody are immobilized onto a nitrocellulose membrane as two distinct lines and combined with a sample pad, a pink/purple 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 1. Reagent 2 is then added and the test strip is placed in the assay tube. Results are read visually at 5 minutes.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Alere PBP2a SA Culture Colony Test, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the reported performance metrics. The study aims to demonstrate substantial equivalence to the predicate device, which itself reports similar performance ranges. The key performance indicators are Sensitivity and Specificity, stratified by plate type.

Metric	Acceptance Criteria (Implied by Predicate)	Alere™ PBP2a SA Culture Colony Test Performance (Sensitivity and Specificity vs. 30µg cefoxitin disk diffusion)
Sensitivity	≥ 91.4% (based on predicate range)	Tryptic Soy Agar (TSA): 99.1% (96.7%, 99.8%)
		Columbia Agar: 98.6% (96.0%, 99.5%)
		Mueller Hinton Plate: 99.1% (96.7%, 99.8%)
Specificity	≥ 92.1% (based on predicate range)	Tryptic Soy Agar (TSA): 99.2% (97.0%, 99.8%)
		Columbia Agar: 99.2% (97.0%, 99.8%)
		Mueller Hinton Plate: 99.6% (97.7%, 99.9%)
Primary Plate Sensitivity	Not explicitly stated, but high	100.0% (129/129) [97.1%, 100.0%]
Primary Plate Specificity	Not explicitly stated, but high	98.5% (134/136) [94.8%, 99.6%]

Note: The acceptance criteria in the table are inferred from the reported performance of the predicate device. The document does not explicitly state pre-defined acceptance criteria for the Alere™ PBP2a SA Culture Colony Test.

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

Test Set Sample Size: A total of 454 S. aureus isolates were evaluated in the multi-center clinical study.
Data Provenance: The study was conducted in three (3) geographically-diverse laboratories in 2013, indicating a multi-site prospective clinical study. The country of origin is not explicitly stated but implies the US given the FDA submission. It is a prospective study as isolates were "evaluated" in the test, suggesting real-time testing.

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

The document does not explicitly state the number of experts used or their specific qualifications.
The ground truth was established by 30 µg cefoxitin disk diffusion interpreted according to Clinical and Laboratory Standards Institute (CLSI) standards. This method is a standardized laboratory procedure, not typically requiring individual expert adjudication in the same way imaging studies might. The interpretation of the disk diffusion results would follow established CLSI guidelines, likely by trained laboratory personnel.

4. Adjudication Method for the Test Set

The ground truth was established by 30 µg cefoxitin disk diffusion interpreted according to CLSI standards. This is a laboratory-based gold standard, not a subjective interpretation requiring an adjudication method like 2+1 or 3+1. Therefore, no multi-reader adjudication method was used for the ground truth.

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

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) test for laboratory use, not an imaging or clinical decision support AI tool designed to assist human readers. Therefore, there is no "human readers improve with AI vs without AI assistance" component.

6. Standalone Performance Study

Yes, the clinical study directly measured the standalone performance of the Alere™ PBP2a SA Culture Colony Test against the ground truth (cefoxitin disk diffusion). The reported sensitivity and specificity values are for the algorithm (device) only, without human-in-the-loop performance.

7. Type of Ground Truth Used

The ground truth used was established by phenotypic susceptibility testing: 30 µg cefoxitin disk diffusion interpreted according to CLSI standards. This is a widely accepted laboratory gold standard for identifying Methicillin-Resistant Staphylococcus aureus (MRSA) and detecting PBP2a expression.

8. Sample Size for the Training Set

The document does not provide information regarding a separate training set or its sample size. The studies described are performance validation studies. For IVD devices, a "training set" in the context of machine learning (AI) is not typically described in 510(k) summaries unless the device incorporates AI. This device relies on immunochromatographic assay principles.

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

As no training set is mentioned in the provided text, there is no information on how its ground truth might have been established. Any internal development and optimization of the assay would have likely used characterized isolates with known PBP2a status, similar to what's described in the analytical studies (e.g., using ATCC strains or strains from repositories like NARSA).

Summary

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

January 13, 2016

ALERE SCARBOROUGH, INC. DANIELLE BRIGGEMAN CLINICAL AFFAIRS SPECIALIST 10 SOUTHGATE ROAD SCARBOROUGH ME 04074

Re: K133851

Trade/Device Name: Alere PBP2a SA Culture Colony Test Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: Class II Product Code: MYI Dated: August 13, 2014 Received: August 20, 2014

Dear Ms. Briggeman:

This letter corrects our substantially equivalent letter of September 03, 2014.

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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

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Page 2 - DANIELLE BRIGGEMAN

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.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809 ), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Ribhi Shawar -S

For Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K133851

Device Name Alere™ PBP2a SA Culture Colony Test

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

2 Prescription Use (Part 21 CFR 801 Subpart D)

_ Over-The-Counter Use (21 CFR 801 Subpart C)

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

FOR FDA USE ONLY

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

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K133851: 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: K133851

SUBMITTER

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

CONTACT PERSON

Danielle A. Briggeman (207) 730-5823 (Office) (207) 730-5767 (FAX) danielle.briggeman@alere.com (email)

ALTERNATE CONTACT PERSON

Angela Drysdale (207) 730-5737 (Office) (207) 730-5767 (FAX) angela.drysdale@alere.com (email)

DATE PREPARED

August 14, 2014

TRADE NAME Alere™ PBP2a SA Culture Colony Test

COMMON NAME

Alere™ SA PBP2a Test, Alere™ PBP2a Staphylococcus aureus Test, Alere™ Culture Colony Test

CLASSIFICATION NAME

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

CLASSIFICATION

Class II

PRODUCT CODE MYI

PANEL Microbiology (83)

PREDICATE DEVICE

Oxoid PBP2' Latex Agglutination Test (#K011710)

Alere™ PBP2a SA Culture Colony Test 510k K133851

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DEVICE DESCRIPTION

INTENDED USE

TECHNOLOGICAL CHARACTERISTICS

The Alere™ PBP2a SA Culture Colony Test and the predicate device, Oxoid PBP2' Latex Agglutination Test, have a similar intended use, indications for use, and utilize similar basic principles of operation. They are both assays for the qualitative detection of PBP2a in isolates sampled directly from culture plates.

DEVICE COMPARISON

The Alere™ PBP2a SA Culture Colony Test was compared to the legally marketed predicate device, Oxoid Penicillin-Binding Protein (PBP2') Latex Agglutination Test.

Parameter	Alere™ PBP2a SA Culture Colony Test	Oxoid Penicillin-Binding Protein (PBP2')Latex Agglutination Test K011710
INTENDED USE	The Alere™ PBP2a SA Culture ColonyTest is a qualitative, in vitroimmunochromatographic assay for therapid detection of penicillin-bindingprotein 2a (PBP2a) in isolates identifiedas Staphylococcus aureus as an aid inidentifying methicillin-resistantStaphylococcus aureus (MRSA).	Same.The test is a rapid latex agglutination assay,detecting PBP2' (also called PBP2a) inisolates of Staphylococcus, as an aid inidentifying methicillin-resistantStaphylococcus aureus (MRSA) andmethicillin-resistant coagulase-negativestaphylococci.
ANALYTE	PBP2a	Same.
TECHNOLOGY	A qualitative, in vitroimmunochromatographic assay	A rapid latex agglutination assay
SPECIMEN TYPE	Isolates identified as S. aureus.	Same.
TIME TO RESULT	5 minutes after sample preparation	Within 3 minutes after sample/testpreparation
PERFORMANCE	Compared to Cefoxitin (30µg) DiskDiffusion (95% confidence intervalsincluded in parenthesis)	Compared to NCCLS methods (95%confidence intervals included in parenthesisand estimated per performance values andknown sample size in product insert)

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Parameter	Alere™ PBP2a SA Culture Colony Test	Oxoid Penicillin-Binding Protein (PBP2')Latex Agglutination Test K011710
	Tryptic Soy Agar with 5% Sheep Blood Plate:
	S. aureus Isolates:Sensitivity: 99.1% (96.7%, 99.8%)Specificity: 99.2% (97.0%, 99.8%)	S. aureus Isolates:Sensitivity: 100.0% (94.7%, 100.0%)Specificity: 99.0% (95.8%, 99.9%)CoNS Isolates:Sensitivity: 96.5% (91.4%, 98.6%)Specificity: 100.0% (92.1%, 100.0%)
	Columbia Agar with 5% Sheep Blood Plate:
	S. aureus Isolates:Sensitivity: 98.6% (96.0%, 99.5%)Specificity: 99.2% (97.0%, 99.8%)	S. aureus Isolates:Sensitivity: 100.0% (94.7%, 100.0%)Specificity: 100.0% (97.1%, 100.0%)CoNS Isolates:Sensitivity: 99.5% (97.4%, 99.9%)Specificity: 99.5% (97.3%, 99.9%)
	Mueller Hinton Plate:
	S. aureus Isolates:Sensitivity: 99.1% (96.7%, 99.8%)Specificity: 99.6% (97.7%, 99.9%)	S. aureus Isolates:Sensitivity: 100.0% (94.7%, 100.0%)Specificity: 100.0% (97.1%, 100.0%)CoNS Isolates:Sensitivity: 95.6% (90.2%, 98.1%)Specificity: 98.0% (88.4%, 99.6%)

PERFORMANCE SUMMARY

CLINICAL STUDIES

The clinical performance of the Alere™ PBP2a SA Culture Colony Test was established in a multi-center clinical study conducted in 2013 at three (3) geographically-diverse laboratories.

A total of 454 S. aureus isolates were evaluated in the Alere™ PBP2a SA Culture Colony Test, compared to results of 30 µg cefoxitin disk diffusion and interpreted according to CLSI standards. Alere™ PBP2a SA Culture Colony Test performance, including 95% confidence intervals, versus cefoxitin disk diffusion, stratified by plate type is provided below.

All positive and negative daily controls generated the expected results.

ALERE™ PBP2A SA CULTURE COLONY TEST PERFORMANCE VS. CEFOXITIN (30μg) DISK DIFFUSION: RESULTS BY PLATE TYPE

S. aureus Isolates

Plate Type	Sensitivity	95% C.I.	Specificity	95% C.I.
Primary Plate1	100.0%(129/129)	(97.1%,100.0%)	98.5%(134/136)	(94.8%,99.6%)
Tryptic Soy Agar with 5% sheep blood	99.1%(213/215)	(96.7%,99.8%)	99.2%(237/239)	(97.0%,99.8%)
Columbia Agar with 5% sheep	98.6%	(96.0%,	99.2%	(97.0%,

Alere™ PBP2a SA Culture Colony Test 510k K133851

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blood	(212/215)	99.5%)	(237/239)	99.8%)
Mueller Hinton with 30µgCefoxitin Induction	99.1%(213/215)	(96.7%,99.8%)	99.6%(238/239)	(97.7%,99.9%)

1: Alere™ PBP2a SA Culture Colony Test was performed from primary plates at 2 out of 3 clinical sites. Primary plates were either Tryptic Soy Agar or Columbia Agar, with the exception of two samples of unknown plate type.

ANALYTICAL STUDIES

Please note: isolates tested in the following studies were not cultured using Columbia agar plates. All positive and negative daily controls generated the expected results.

ANALYTICAL SENSITIVITY

Alere™ PBP2a SA Culture Colony Test limit of detection (LOD or C35), defined as the concentration of PBP2a producing Staphylococi that produces positive Alere™ PBP2a SA Culture Colony Test results approximately 95% of the time, was identified by evaluating different concentrations of one (1) PBP2a producing S. aureus isolate . The concentration identified as the LOD (or C95) level is listed below.

Staphylococcus species	Concentration(CFU/ml)	# Detected per TotalTests	% Detected
S. aureus (ATCC BAA44)	7.30 x $10^8$	19/20	95%

REACTIVITY TESTING

162 strains of methicillin resistant Staphylococcus aureus were tested with the Alere™ PBP2a SA Culture Colony Test with positive results. The strains were obtained from the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA), American Type Culture Collection (ATCC) and Department of Infectious Disease Epidemiology of the Imperial College in London, England.

ANALYTICAL SPECIFICITY (CROSS-REACTIVITY)

To determine the analytical specificity of the Alere™ PBP2a SA Culture Colony Test, the following list of methicillinsensitive Staphylococcus aureus (MSSA) and non-Staphylococcal strains were tested. All of the organisms tested were negative. When more than one strain was tested, the number is listed in parenthesis.

Species
Staphylococcus aureus (MSSA) (112)
Non-Staphylococcal Strains:
Aerococcus urinae
Planococcus citreus
Kytococcus schroeteri
Stomatococcus (Rothia mucilanginosa)
Kocuria kristinae
Micrococcus luteus

REPRODUCIBILITY

Alere™ PBP2a SA Culture Colony Test 510k K133851

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The Alere™ PBP2a SA Culture Colony Test reproducibility study was conducted at 3 separate sites using panels of blind coded specimens containing negative samples in duplicate for each panel. Participants (2 per site) each tested one panel on 5 different days. There was 100.0% (600/600) agreement with expected test results for Staphylococcus aureus. There were no significant differences within run (replicates tested by one operator), between run (5 different days), between sites (3 sites), or between operators (6 operators).

Signed: _

Date: ________________________________________________________________________________________________________________________________________________________________________

Angela Drysdale VP, Regulatory & Clinical Affairs – Infectious Disease Alere Scarborough, Inc.

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).