VISUWELL REAGIN II

K952802 · Biomira Diagnostics, Inc. · GMQ · May 23, 1996 · Microbiology

Device Facts

• Record ID: K952802
• Device Name: VISUWELL REAGIN II
• Applicant: Biomira Diagnostics, Inc.
• Product Code: GMQ · Microbiology
• Decision Date: May 23, 1996
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3820
• Device Class: Class 2

Indications for Use

Visuwell® Reagin II is an enzyme-linked immunosorbent assay for the in vitro qualitative detection of non-treponemal (reagin) antibodies as a screening test in syphilis serology. It is not intended for use in screening blood or plasma donors.

Device Story

Visuwell® Reagin II is an ELISA kit for detecting non-treponemal (reagin) antibodies in human serum. The device uses a polystyrene solid phase coated with a mixture of cardiolipin, lecithin, and cholesterol. Patient serum is incubated with this antigen; if reagin antibodies are present, they form an immune complex. A monoclonal anti-human IgG-peroxidase conjugate binds to these complexes. After adding an enzyme substrate, color develops, which is stopped by acid and measured spectrophotometrically at 450 nm. Results are interpreted against a floating cutoff derived from a negative control. The device is intended for laboratory use as a syphilis screening tool. It provides objective, quantitative spectrophotometric data compared to the subjective flocculation-based visual interpretation of traditional reference tests (VDRL, RPR, RST).

Clinical Evidence

Clinical evaluation included 11,443 specimens across random, low-risk, high-risk, and disease-specific populations. Specificity was 97.1% (vs 99.5% for reference). Sensitivity in untreated syphilis was 92.2% (vs 95.8% for reference). Predictive value of positive was 97.4% (vs 99.4% for reference); predictive value of negative was 99.0% (vs 99.5% for reference). Overall agreement with reference tests was 96.5%. Cross-reactivity testing included 151 specimens from patients with bacterial, viral, and auto-immune disorders, showing 86.8% specificity (vs 91.9% for reference).

Technological Characteristics

ELISA-based immunoassay. Solid phase: polystyrene coated with cardiolipin, lecithin, and cholesterol. Detection: monoclonal anti-human IgG-peroxidase conjugate. Signal measurement: spectrophotometric at 450 nm. Interpretation: floating cutoff based on negative control. In vitro diagnostic reagent kit.

Indications for Use

Indicated for in vitro qualitative screening of non-treponemal (reagin) antibodies in human serum for syphilis serology. Not for blood or plasma donor screening.

Regulatory Classification

Identification

Treponema pallidum nontreponemal test reagents are devices that consist of antigens derived from nontreponemal sources (sources not directly associated with treponemal organisms) and control sera (standardized sera with which test results are compared) used in serological tests to identify reagin, an antibody-like agent, which is produced from the reaction of treponema microorganisms with body tissues. The identification aids in the diagnosis of syphilis caused by microorganisms belonging to the genus Treponema and provides epidemiological information on syphilis.

Reference Devices

• Venereal Disease Research Laboratory (VDRL) Slide Test
• Rapid Plasma Reagin (RPR) Card Test
• Reagin Screen Test (RST)

Submission Summary (Full Text)

{0}

K952802
BIOMIRA
DIAGNOSTICS INC.

MAY 23 1995

# 510(k) SUMMARY VISUWELL® REAGIN II

This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirements of the Safety Medical Devices Act of 1990.

## Submitter:

BIOMIRA Diagnostics Inc.
30 Meridian Rd.
Rexdale, Ontario
M9W 4Z7
Contact: Ms. Althea R. Lawrence, Director, Quality/Regulatory

## Date Submitted:

June 16, 1995

## Device Name:

*Trade Name:* Visuwell® Reagin II

*Common Name:* Syphilis non-treponemal antibody detection kit

*Classification Name:* Treponemal pallidum non-treponemal test reagent, Class II

## Device Description:

Visuwell® Reagin II is an enzyme-linked immunosorbent assay for the *in vitro* qualitative detection of non-treponemal (reagin) antibodies in syphilis serology. In this device, serum is incubated with a mixture of cardiolipin, lecithin, cholesterol dried to a polystyrene solid phase.

PAGE 1 OF 5

BIOMIRA Diagnostics Inc., 30 Meridian Road, Rexdale, Ontario, Canada M9W 4Z7
Tel: [phone] Fax: [phone] (Rest of Canada)

{1}

BIOMIRA DIAGNOSTICS INC.

# 510(k) SUMMARY VISUWELL® REAGIN II

Antilipid antibodies react with the lipoidal antigen to form an immune complex. The presence of non-treponemal complexed antibodies is detected with a monoclonal anti-human IgG-peroxidase conjugate. The presence of bound conjugate is detected by the addition of enzyme substrate and subsequent development of colour. The reaction is stopped by the addition of acid and colour intensity is determined spectrophotometrically at 450 nm.

Test results are interpreted relative to a floating cutoff based on the negative control. Positive and negative controls are used for establishing test validity.

## Intended Use

Visuwell® Reagin II is an enzyme-linked immunosorbent assay for the *in vitro* qualitative detection of non-treponemal (reagin) antibodies as a screening test in syphilis serology. It is not intended for use in screening blood or plasma donors.

## Substantial Equivalence Claim

Visuwell® Reagin II was demonstrated to be substantially equivalent in performance to the following legally marketed reference non-treponemal tests:

Venereal Disease Research Laboratory (VDRL) Slide Test
Rapid Plasma Reagin (RPR) Card Test
Reagin Screen Test (RST)

Visuwell® Reagin II has the same intended use for screening in syphilis serology but different technological characteristics than the above mentioned reference tests. These tests employ lipoidal antigen comprised of cardiolipin, lecithin and cholesterol.

PAGE 2 OF 5

BIOMIRA Diagnostics Inc., 30 Meridian Road, Rexdale, Ontario, Canada M9W 4Z7
Tel: [phone] Fax: [phone] (Rest of Canada)

{2}

BIOMIRA DIAGNOSTICS INC.

# 510(k) SUMMARY VISUWELL® REAGIN II

Results in the reference tests are interpreted subjectively according to the presence or absence of flocculation as opposed to the objective spectrophotometric interpretation of results using Visuwell® Reagin II.

To demonstrate substantial equivalence, Visuwell® Reagin was compared to the reference tests in specificity, sensitivity, predictive values, cross-reactivity and overall agreement of test results.

## Specificity Comparison

Specificity results were obtained from 10,738 specimens in random, low-risk and high-risk populations. The specificity of Visuwell® Reagin II was 97.1% compared to the 99.5% specificity of the reference non-treponemal tests. Visuwell® Reagin II is substantially equivalent to non-treponemal reference tests in specificity.

## Sensitivity Comparison

Sensitivity results were obtained from the specimens of 306 patients with untreated syphilis, 74 patients whose treatment status was unknown and 325 patients with treated syphilis.

Visuwell® Reagin II was reactive with 92.2% of specimens from patients with untreated syphilis as compared to 95.8% of specimens with the reference tests. Where treatment status of the patients was unknown, Visuwell® Reagin II was reactive with 93.2% of the specimens as compared to 82.4% of the specimens with the reference tests. Visuwell® Reagin II was reactive with 75.4% of specimens from patients with treated syphilis as compared to 90.2% of the specimens with the reference tests.

PAGE 3 OF 5

BIOMIRA Diagnostics Inc., 30 Meridian Road, Rexdale, Ontario, Canada M9W 4Z7
Tel: [phone] Fax: [phone] (Rest of Canada)

{3}

BIOMIRA DIAGNOSTICS INC.

# 510(k) SUMMARY VISUWELL® REAGIN II

Therefore, Visuwell® Reagin II is substantially equivalent to reference non-treponemal tests in the detection of non-treponemal antibody in sera of patients with untreated syphilis. Visuwell® Reagin II shows lower reactivity with sera from patients with treated syphilis which may suggest potential for monitoring response to therapy.

## Predictive Values

The predictive values of positive for syphilis in Visuwell® Reagin II and the reference tests were determined for the Sexually Transmitted Disease (STD) population. The predictive values of negative were determined with data from all sites. The predictive value of positive for Visuwell® Reagin II was 97.4% as compared to 99.4% for the reference tests. The predictive value of negative for Visuwell® Reagin II was 99.0% as compared to 99.5% for the reference tests.

Consequently, Visuwell® Reagin II is substantially equivalent to reference tests in predictive value of positive for STD populations and predictive value of negative.

## Cross-Reactivity

Cross-Reactivity results were obtained from 151 specimens consisting of specimens from individuals with a variety of bacterial, viral and auto-immune disorders. Specimens identified as syphilis biological false-positives and specimens from conditions frequently associated with false reactivity in non-treponemal screen tests such as pregnancy and drug abuse were included in these results.

BIOMIRA Diagnostics Inc., 30 Meridian Road, Rexdale, Ontario, Canada M9W 4Z7
Tel: [phone] Fax: [phone] (Rest of Canada)

{4}

BIOMIRA DIAGNOSTICS INC.

# 510(k) SUMMARY VISUWELL® REAGIN II

The specificity of Visuwell® Reagin II in the clinical population characterized by non-syphilitic diseases or conditions was 86.8% as compared to 91.9% with the reference tests. These results indicate that the performance of Visuwell® Reagin II is substantially equivalent to the reference tests for specimens that have potential for interference.

## Overall Agreement

The overall agreement between the Visuwell® Reagin II and the reference tests results for all sera (11,443 specimens) was 96.5%. Visuwell® Reagin II is substantially equivalent to non-treponemal reference tests in overall agreement of test results.

## Conclusion

The safety and effectiveness of Visuwell® Reagin II is substantially equivalent to legally marketed non-treponemal reference tests (VDRL, RPR, RST) as demonstrated in the comparison of the performance of Visuwell® Reagin to these tests.

PAGE 5 OF 5

BIOMIRA Diagnostics Inc., 30 Meridian Road, Rexdale, Ontario, Canada M9W 4Z7
Tel: [phone] Fax: [phone] (Rest of Canada)