ALERE PBP2A SA/CONS CULTURE COLONY TEST

K133851 · Alere Scarborough, Inc. · MYI · Sep 3, 2014 · Microbiology

Device Facts

• Record ID: K133851
• Device Name: ALERE PBP2A SA/CONS CULTURE COLONY TEST
• Applicant: Alere Scarborough, Inc.
• Product Code: MYI · Microbiology
• Decision Date: Sep 3, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.1640
• Device Class: Class 2

Intended Use

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 Story

Rapid immunochromatographic membrane assay; detects PBP2a protein in S. aureus isolates. Input: bacterial colonies sampled from culture plates (Tryptic Soy Agar, Columbia Agar, or Mueller-Hinton Agar). Process: isolates eluted into Reagent 1; Reagent 2 added; test strip inserted. Principle: recombinant monoclonal antibody fragments (rFabs) immobilized on nitrocellulose membrane bind PBP2a. Output: visual pink/purple line at 5 minutes. Used in clinical microbiology laboratories; operated by laboratory technicians. Results aid clinicians in identifying MRSA, facilitating appropriate antimicrobial therapy decisions.

Clinical Evidence

Multi-center clinical study (3 sites, 454 S. aureus isolates) compared the device to 30µg cefoxitin disk diffusion. Performance varied by plate type: Primary plates (100% sensitivity, 98.5% specificity), Tryptic Soy Agar (99.1% sensitivity, 99.2% specificity), Columbia Agar (98.6% sensitivity, 99.2% specificity), and Mueller Hinton (99.1% sensitivity, 99.6% specificity). Reproducibility study (3 sites, 6 operators) showed 100% agreement (600/600) across runs, sites, and operators.

Technological Characteristics

Immunochromatographic membrane assay. Components: nitrocellulose membrane, sample pad, conjugate pad, absorption pad. Reagents: rFabs and control antibody immobilized on membrane. Form factor: dipstick/test strip. Visual readout. No electronic components or connectivity. Sterilization: not specified.

Indications for Use

Indicated for the qualitative detection of PBP2a in Staphylococcus aureus isolates to aid in the identification of MRSA. For prescription use.

Regulatory Classification

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.

Predicate Devices

• Oxoid Penicillin-Binding Protein (PBP2a) Latex Agglutination Test (K011710)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, with flowing lines connecting them.

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 [phone] or [phone] 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 [phone] or [phone] 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)

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).

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)

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#### 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 [phone] (Office) [phone] (FAX) [e-mail] (email)

# ALTERNATE CONTACT PERSON

Angela Drysdale [phone] (Office) [phone] (FAX) [e-mail] (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

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.

# INTENDED USE

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).

# 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')<br>Latex Agglutination Test K011710 |
|----------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| INTENDED USE | The Alere™ PBP2a SA Culture Colony<br>Test is a qualitative, in vitro<br>immunochromatographic assay for the<br>rapid detection of penicillin-binding<br>protein 2a (PBP2a) in isolates identified<br>as Staphylococcus aureus as an aid in<br>identifying methicillin-resistant<br>Staphylococcus aureus (MRSA). | Same.<br>The test is a rapid latex agglutination assay,<br>detecting PBP2' (also called PBP2a) in<br>isolates of Staphylococcus, as an aid in<br>identifying methicillin-resistant<br>Staphylococcus aureus (MRSA) and<br>methicillin-resistant coagulase-negative<br>staphylococci. |
| ANALYTE | PBP2a | Same. |
| TECHNOLOGY | A qualitative, in vitro<br>immunochromatographic 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/test<br>preparation |
| PERFORMANCE | Compared to Cefoxitin (30µg) Disk<br>Diffusion (95% confidence intervals<br>included in parenthesis) | Compared to NCCLS methods (95%<br>confidence intervals included in parenthesis<br>and estimated per performance values and<br>known sample size in product insert) |

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| Parameter | Alere™ PBP2a SA Culture Colony Test | Oxoid Penicillin-Binding Protein (PBP2')<br>Latex Agglutination Test K011710 |
|-----------|------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Tryptic Soy Agar with 5% Sheep Blood Plate: | |
| | <i>S. aureus</i> Isolates:<br>Sensitivity: 99.1% (96.7%, 99.8%)<br>Specificity: 99.2% (97.0%, 99.8%) | <i>S. aureus</i> Isolates:<br>Sensitivity: 100.0% (94.7%, 100.0%)<br>Specificity: 99.0% (95.8%, 99.9%)<br>CoNS Isolates:<br>Sensitivity: 96.5% (91.4%, 98.6%)<br>Specificity: 100.0% (92.1%, 100.0%) |
| | Columbia Agar with 5% Sheep Blood Plate: | |
| | <i>S. aureus</i> Isolates:<br>Sensitivity: 98.6% (96.0%, 99.5%)<br>Specificity: 99.2% (97.0%, 99.8%) | <i>S. aureus</i> Isolates:<br>Sensitivity: 100.0% (94.7%, 100.0%)<br>Specificity: 100.0% (97.1%, 100.0%)<br>CoNS Isolates:<br>Sensitivity: 99.5% (97.4%, 99.9%)<br>Specificity: 99.5% (97.3%, 99.9%) |
| | Mueller Hinton Plate: | |
| | <i>S. aureus</i> Isolates:<br>Sensitivity: 99.1% (96.7%, 99.8%)<br>Specificity: 99.6% (97.7%, 99.9%) | <i>S. aureus</i> Isolates:<br>Sensitivity: 100.0% (94.7%, 100.0%)<br>Specificity: 100.0% (97.1%, 100.0%)<br>CoNS Isolates:<br>Sensitivity: 95.6% (90.2%, 98.1%)<br>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%<br>(129/129) | (97.1%,<br>100.0%) | 98.5%<br>(134/136) | (94.8%,<br>99.6%) |
| Tryptic Soy Agar with 5% sheep blood | 99.1%<br>(213/215) | (96.7%,<br>99.8%) | 99.2%<br>(237/239) | (97.0%,<br>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 30µg<br>Cefoxitin Induction | 99.1%<br>(213/215) | (96.7%,<br>99.8%) | 99.6%<br>(238/239) | (97.7%,<br>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<br>(CFU/ml) | # Detected per Total<br>Tests | % Detected |
|-------------------------------|---------------------------|-------------------------------|------------|
| <i>S. aureus</i> (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.