COPALIS CMV TOTAL ANTIBODY ASSAY

K955799 · Sienna Biotech, Inc. · LJO · Jul 10, 1996 · Microbiology

Device Facts

• Record ID: K955799
• Device Name: COPALIS CMV TOTAL ANTIBODY ASSAY
• Applicant: Sienna Biotech, Inc.
• Product Code: LJO · Microbiology
• Decision Date: Jul 10, 1996
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3175
• Device Class: Class 2

Intended Use

The Copalis™ CMV Total Antibody Assay uses Coupled Particle Light Scattering (Copalis™) technology in a microparticle agglutination-based immunoassay for the qualitative and semi-quantitative detection of total antibodies (IgG and IgM) to cytomegalovirus (CMV) in human serum using the Copalis™ One Immunoassay System. The presence of antibodies is indicative of current or prior infection with the suspected organism. The results of this assay on a single serum specimen are used to indicate presence of antibody to CMV. When evaluating properly paired sera, the results of this assay are used to demonstrate seroconversion or a significant increase in antibody level as evidence of recent infection. Both specimens should be tested simultaneously (see Interpretation of Results). This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

Device Story

Copalis™ CMV Total Antibody Assay utilizes Coupled Particle Light Scattering (Copalis™) technology for CMV antibody detection. Input: human serum specimen. Principle: antibody-dependent particle aggregation; latex particles coated with inactivated CMV antigens aggregate when CMV antibodies are present. Process: 10-minute agitation; flow-based detection measuring reacted vs. unreacted particles; aggregation level compared to cutoff value. Output: qualitative/semi-quantitative antibody presence. Used in clinical laboratory settings with Copalis™ One Immunoassay System. Results assist clinicians in diagnosing current or prior CMV infection and identifying recent infection via paired sera analysis (seroconversion/titer increase).

Clinical Evidence

Clinical comparison of 689 patient sera samples across 3 sites vs. CMVscan Test showed 97.6% relative sensitivity, 97.8% relative specificity, and 97.7% relative agreement. Reproducibility studies (4 samples, 5 runs, 6 replicates) showed low %CV. CDC serum panel (66% positive, 34% negative) showed 100% agreement. Interference testing confirmed no cross-reactivity with RF, ANA, HSV, EBV, VZV, or rubella antibodies.

Technological Characteristics

Microparticle agglutination immunoassay using Coupled Particle Light Scattering (Copalis™). Employs latex particles coated with inactivated CMV antigens. System includes Copalis™ One Immunoassay System for flow-based particle detection. Quantitative output based on light scattering changes proportional to particle aggregation.

Indications for Use

Indicated for qualitative and semi-quantitative detection of total (IgG and IgM) antibodies to cytomegalovirus (CMV) in human serum to identify current or prior infection. Not for blood or plasma donor screening.

Regulatory Classification

Identification

Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.

Predicate Devices

• Becton Dickinson and Co. CMVscan Test

Submission Summary (Full Text)

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K955799
JUL 10 1996

# VII. SUMMARY OF SAFETY AND EFFECTIVENESS

This summary of safety and effectiveness information is being submitted in accordance with the requirements of the Safe Medical Devices Act of 1990.

## DATE OF SUMMARY PREPARATION:

June 26, 1996

## MANUFACTURER:

Sienna Biotech, Inc.
9115 Guilford Rd.
Columbia, MD 21046-1893

## 510(k) CONTACT PERSON:

Judith J. Smith
Director, Regulatory Affairs and Quality Management
[phone] x256

## NAME OF DEVICE:

Copalis™ CMV Total Antibody Assay

## COMMON NAME:

Immunoassay for the detection of total antibody to CMV

## PREDICATE DEVICE:

Becton Dickinson and Co.
CMVscan Test

## DEVICE DESCRIPTION:

Intended Use: The Copalis™ CMV Total Antibody Assay uses Coupled Particle Light Scattering (Copalis™) technology in a microparticle agglutination-based immunoassay for the qualitative and semi-quantitative detection of total antibodies (IgG and IgM) to cytomegalovirus (CMV) in human serum using the Copalis™ One Immunoassay System. The presence of antibodies is indicative of current or prior infection with the suspected organism. The results of this assay on a single serum specimen are used to indicate presence of antibody to CMV. When evaluating properly paired sera, the results of this assay are used to demonstrate seroconversion or a significant increase in antibody level as evidence of recent infection. Both specimens should be tested simultaneously (see Interpretation of Results). This assay has not been FDA cleared or approved for the screening of blood or plasma donors.

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Kit Description: Coupled Particle Light Scattering (Copalis) technology provides a rapid method for the measurement of antibodies to specific viral or bacterial pathogens.

The Copalis CMV Total Antibody Assay is based on the principle of antibody-dependent particle aggregation as detected by measurement of changes in light scattering. Latex particles coated with inactivated CMV antigens aggregate in the presence of antibodies to CMV. After 10 minutes of agitation, the level of aggregation is determined by measurement of the number of reacted and unreacted particles as they flow past a detector. The number of reacted particles is related to the level of CMV antibodies present in the test specimen. Without prior infection, antibody levels are absent or low. After infection, antibody levels rise and usually remain stable (but declining in titer) for years. Reactivity is assessed by the level of aggregation relative to a cutoff value. The Copalis CMV Assay detects the presence of both IgM and IgG antibodies. Two levels of controls are used to monitor proficiency.

## PERFORMANCE DATA:

Clinical Comparison: Six hundred eighty-nine (689) patient sera samples representing the mid-Atlantic and Gulf Coast regions of the U.S. were tested at 2 clinical laboratories and at Sienna Biotech Inc. In the study, the Copalis CMV Total Antibody Assay was compared to the Becton Dickinson and Co. CMVscan Test. Combined site relative sensitivity and specificity were 97.6% and 97.8%, respectively; combined site relative agreement was 97.7%.

Reproducibility: Reproducibility studies were performed at the 3 sites using one lot of TORC tests. Assay reproducibility was determined by testing four (4) samples across a range of reactivity. Five (5) runs of six (6) replicates of each sample were tested over three days. Results are presented below by clinical trial site:

| Level | Mean (CTR) | Within Assay %CV | Between Assay %CV | Mean (CTR) | Within Assay %CV | Between Assay %CV | Mean (CTR) | Within Assay %CV | Between Assay %CV |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| RP1 | 100 | 2.2 | 0.0 | 100 | 2.0 | 0.6 | 101 | 1.6 | 0.4 |
| RP2 | 114 | 2.8 | 0.0 | 124 | 3.0 | 1.5 | 128 | 4.5 | 1.0 |
| RP3 | 133 | 3.5 | 0.0 | 157 | 4.4 | 0.8 | 161 | 5.1 | 3.9 |
| RP4 | 174 | 5.3 | 1.7 | 210 | 6.3 | 2.0 | 222 | 8.8 | 3.2 |

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During the clinical trials, the Low Positive Control which is near the assay cutoff was assayed with each tray. Results are summarized below:

Low Positive Control Total Precision

| Site | Mean (CTR) | S.D. | %CV | Min | Max |
| --- | --- | --- | --- | --- | --- |
| #1 | 120 | 5.3 | 4.4 | 113 | 136 |
| #2 | 119 | 4.9 | 4.1 | 111 | 134 |
| #3 | 125 | 5.0 | 4.0 | 114 | 140 |

Reproducibility of the conversion coefficient was also evaluated at the 3 trial sites. Thirty sets of a simulated acute and convalescent pair were analyzed over several days at each site. Reproducibility was expressed as the percent of those sets which met the conversion coefficient criterion for significant rise in antibody level. Of the 30 sets per site, 30, 19 and 29 sets met the criterion of $\geq 50\%$, representing $100\%$, $63\%$ and $97\%$ agreement for sites 1, 2 and 3, respectively.

**CDC CMV Serum Panel**: The following information is from a serum panel obtained from the CDC and tested by Sienna Biotech, Inc. The results are presented as a means to convey further information of the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.

The panel consists of $66\%$ positive and $34\%$ negative samples. The Copalis CMV Total Antibody Assay demonstrated $100\%$ total agreement with the CDC results.

**Interfering Substances**: Testing was conducted at Sienna Biotech, Inc. to demonstrate that rheumatoid factor (RF) and antinuclear antibodies (ANA) do not interfere with the performance of the assay. In addition, patient samples containing antibodies to HSV, EBV, VZV, and rubella were tested. None of these factors or antibodies interfered with the Copalis CMV assay results.

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