COPALIS TREPONEMAL ANTIGEN TOTAL ANTIBODY ASSAY

K992552 · DiaSorin, Inc. · LIP · Dec 16, 1999 · Microbiology

Device Facts

• Record ID: K992552
• Device Name: COPALIS TREPONEMAL ANTIGEN TOTAL ANTIBODY ASSAY
• Applicant: DiaSorin, Inc.
• Product Code: LIP · Microbiology
• Decision Date: Dec 16, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3830
• Device Class: Class 2

Intended Use

The Copalis Treponemal Antibody Assay uses Coupled Particle Light Scattering (Copalis®) technology in a microparticle agglutination-based immunoassay for the qualitative detection of total antibodies (IgG and IgM) to recombinant Treponema pallidum antigens in human serum using the Copalis I Immunoassay System. The presence of antibodies is indicative of current or prior infection with T. pallidum. The assay is indicated as an aid in the serological confirmation of syphilis disease following a positive result with a nontreponemal screening test. This assay has not been FDA cleared or approved for the screening of blood or plasma donors. NOTE: The Copalis Treponemal Antibody Assav has not been evaluated as an initial or single test for the serodiagnosis of syphilis. The predictive value of a positive Copalis Treponemal Antibody Assay result has not been determined with RPR negative specimens.

Device Story

Device uses Coupled Particle Light Scattering (Copalis) technology to detect total antibodies (IgG/IgM) to T. pallidum in human serum. Polystyrene microparticles coated with recombinant T. pallidum antigen are reconstituted with buffer; patient sample added and incubated for 10 minutes. Specific antibodies cause microparticle agglutination. Reaction mixture passes through flow cell; instrument measures monomer concentration via light scattering. Decrease in monomer population correlates to antibody concentration. Residual monomer concentration compared to cutoff value determines reactivity. Used in clinical laboratories by trained personnel. Output assists clinicians in confirming syphilis diagnosis following positive nontreponemal screening. Benefits include rapid, automated detection of T. pallidum antibodies.

Clinical Evidence

Clinical trials at four sites evaluated performance against FTA-ABS and TP-PA. 188 syphilis-diagnosed patients and 2086 additional sera (including CDC/commercial panels) were tested. Sensitivity ranged from 66.7% to 100% depending on disease stage and treatment status. Specificity was 100% in tested cohorts. Agreement with confirmatory tests was 96.3% for RPR-positive samples and 100% for characterized commercial panels. Reproducibility studies showed total %CV ranging from 1.4% to 18.0% across six samples.

Technological Characteristics

Uses Coupled Particle Light Scattering (Copalis) technology. Reagents consist of polystyrene microparticles coated with recombinant T. pallidum antigen. System includes a flow cell for light scattering measurement. Operates on the Copalis I Immunoassay System. Qualitative immunoassay format.

Indications for Use

Indicated for qualitative detection of total antibodies (IgG and IgM) to Treponema pallidum in human serum as an aid in syphilis confirmation following a positive nontreponemal screening test. Not for blood/plasma donor screening or as an initial/single test for syphilis serodiagnosis.

Regulatory Classification

Identification

Treponema pallidum treponemal test reagents are devices that consist of the antigens, antisera and all control reagents (standardized reagents with which test results are compared) which are derived from treponemal sources and that are used in the fluorescent treponemal antibody absorption test (FTA-ABS), the Treponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies to Treponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genus Treponema and provides epidemiological information on syphilis.

Predicate Devices

• Zeus Scientific Inc. FTA-ABS
• FUJIREBIO INC. SERODIA® TP-PA

Submission Summary (Full Text)

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DEC I 6 1999

K992552

December 10, 1999

## 510(K) SUMMARY

| SUBMITTED BY: | Judith J. Smith<br>Vice President,<br>Worldwide Regulatory Affairs and Quality Systems |
|----------------------------|----------------------------------------------------------------------------------------|
| NAME OF DEVICES: | |
| Trade Name: | Copalis Treponemal Antigen Total Antibody Assay |
| Common Names/Descriptions: | Immunoassay for the Detection of Total Antibodies<br>to Treponema pallidum |
| Classification Names: | Treponema pallidum treponemal test |
| PREDICATE DEVICES: | Zeus Scientific Inc. FTA-ABS and FUJIREBIO INC.<br>SERODIA® TP-PA |

DEVICE DESCRIPTION:

INTENDED USE: The Copalis Treponemal Antibody Assay uses Coupled Particle Light Scattering (Copalis®) technology in a microparticle agglutination-based immunoassay for the qualitative detection of total antibodies (IgG and IgM) to recombinant Treponema pallidum antigens in human serum using the Copalis I Immunoassay System. The presence of antibodies is indicative of current or prior infection with T. pallidum. The assay is indicated as an aid in the confirmation of syphilis disease following a positive result with a nontreponemal screening test. This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

KIT DESCRIPTION: The Copalis® Treponemal Antigen Total Antibody Assay is based on Coupled Particle Light Scattering (Copalis) technology which provides a rapid method for the measurement of antibodies to specific pathogens.

The assay is a microparticle agglutination test using the Copalis light scattering technology. Polystyrene microparticles are coated with recombinant antigen derived from T. pallidum and are contained within a special covered reaction well in the test cup. The dried reagent is reconstituted with a reaction buffer on the instrument at the start of the assay. Patient sample is added to the reaction mixture and incubated for 10 minutes. The presence of antibodies specific to T. pallidum in the patient sample results in agglutination of the monomer microparticles to form aggregrates. The reaction mixture is passed through a flow cell and the instrument uses light scattering technology to measure the monomer concentration. The decrease in the monomer population resulting from agglutination is related to the amount of antibody in the sample. The residual monomer concentration in each reaction mixture is compared to a cutoff value to determine sample reactivity and nonreactivity.

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## PERFORMANCE DATA:

Clinical Correlation: Clinical trials were conducted at four sites (2 clinical laboratories, 1 reference laboratory and the laboratory located at DiaSorin Inc.) to evaluate the performance of the Copalis Treponemal Antibody Assay in detecting antibodies to Treponema pallidum on the Copalis I Immunoassay System. The assay performance was compared to the Zeus Scientific Inc. FTA-ABS assay and the FUJIREBIO Inc. TP-PA, both of which are confirmatory tests.

Samples from 188 patients with diagnosis of syphilis were analyzed using the Copalis® Treponemal Antigen Total Antibody Assay. These samples were characterized by disease state and treatment status. The clinical sensitivity of the assay is shown below.

| Stage | Treatment<br>Status | Copalis<br>Sensitivity<br>RPR + FTA + | Copalis<br>Sensitivity<br>RPR - FTA + | Copalis<br>Specificity<br>RPR +/- FTA - |
|----------------|---------------------|---------------------------------------|---------------------------------------|-----------------------------------------|
| Primary | Untreated | 100%<br>(15.8-100%) | -- | 100%<br>(2.5-100%) |
| | Treated | 100%<br>(75.3-100%) | 66.7%<br>(22.2-95.7%) | 100%<br>(2.5-100%) |
| Secondary | Untreated | 100%<br>(86.3-100%) | -- | -- |
| | Treated | 100%<br>(88.1-100%) | 100%<br>(2.5-10%) | -- |
| Latent | Treated | 97.8%<br>(92.2-99.7%) | 100%<br>(66.4-100%) | 100%<br>(15.8-100%) |
| Late, | | 100%<br>(29.2-100%) | 100%<br>(2.5-100%) | -- |
| Cardiovascular | | 100%*<br>(15.8-100%) | 100%<br>(15.8-100%) | -- |
| Congenital | | | | |

## Clinical Sensitivity and 95% Confidence Limits From Syphilitic Sera:

*excludes 1 equivocal result

In addition, 2086 sera from a variety of diseases and 45 CDC or commercial panel samples were tested. The results are summarized below.

| Category | Number | Agreement |
|-----------------------------------------------------------------------------------|--------|-----------------------------------------------------------------------|
| RPR positive samples sent to hospital<br>laboratories for confirmation of disease | 1005 | 96.3%<br>(944/980)<br>(25 equivocal) |
| Apparently healthy adults | 1002 | Prevalence:<br>Copalis = 3.2%<br>(32/1002)<br>FTA = 2.2%<br>(22/1002) |
| Other (Obstetric; Pediatric >18 months<br>old) | 35 | 100%<br>(34/34)<br>(1 Copalis eq/FTA -) |

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| Category | Number | Agreement |
|--------------------------------------------------------|--------|-----------------|
| CDC Panel | 20 | 90%<br>(18/20) |
| Characterized commercial syphilis<br>mixed titer panel | 25 | 100%<br>(25/25) |

Reproducibility: Reproducibility studies were performed at the 3 sites using one lot of reagents. Assay reproducibility was determined by testing 6 samples that spanned the range of the assay's CTRs. Samples were tested in duplicate once a day for 5 days. The results are summarized below.

COPALIS TREPONEMAL ASSAY REPRODUCIBILITY RESULTS COMBINED SITES CTR

| SAMPLE | MEAN CTR | WITHIN<br>RUN %CV | TOTAL<br>%CV |
|------------------|----------|-------------------|--------------|
| Negative Control | 101 | - | 1.4 |
| Positive Control | 171 | - | 8.7 |
| RP1 | 103 | 1.4 | 1.9 |
| RP2 | 1470 | 16.2 | 18.0 |
| RP3 | 101 | 1.5 | 1.8 |
| RP4 | 280 | 13.1 | 16.7 |
| RP5 | 1068 | 12.9 | 16.7 |
| RP6 | 172 | 7.6 | 13.3 |

The Copalis TTA Quality Control procedures include the running of a negative and a positive control at least every 24 hours of use. This procedure was followed by all sites during the clinical trials. A summary of the control data is presented here.

## CONTROL RESULTS, SITES COMBINED

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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 caduceus, which is a symbol often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus.

DEC I 6 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Judith J. Smith Vice President Worldwide Regulatory Affairs and Quality Systems DiaSorin, Inc. 9175 Guilford Road Quarry Park Place, Suite 100 Columbia, Maryland 21046

- Re: K992552
Trade Name: DiaSorin Copalis™ Treponemal Antigen Total Antibody Assay Regulatory Class: II Product Code: LIP Dated: October 20, 1999 Received: October 25, 1999

Dear Ms. Smith:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 either class II (Special Controls) or class III (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 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 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): K992552

Device Name: DiaSorin Copalis®Treponemal Antigen Total Antibody Assay

Indications For Use:

The Copalis Treponemal Antibody Assay uses Coupled Particle Light Scattering (Copalis®) technology in a microparticle agglutination-based immunoassay for the qualitative detection of total antibodies (IgG and IgM) to recombinant Treponema pallidum antigens in human serum using the Copalis I Immunoassay System. The presence of antibodies is indicative of current or prior infection with T. pallidum. The assay is indicated as an aid in the serological confirmation of syphilis disease following a positive result with a nontreponemal screening test. This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

NOTE: The Copalis Treponemal Antibody Assav has not been evaluated as an initial or single test for the serodiagnosis of syphilis. The predictive value of a positive Copalis Treponemal Antibody Assay result has not been determined with RPR negative specimens.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubois

vision of Clinical Laboratory Devices K 992552 510(k) Number ...

Prescription Use (Per 21 CFR 801.109)

OR

Over-The-Counter Use

(Optional Format 1-2-96)