VCA IGM ELISA TEST SYSTEM

K980596 · Clark Laboratories, Inc. · LSE · Jul 22, 1998 · Microbiology

Device Facts

• Record ID: K980596
• Device Name: VCA IGM ELISA TEST SYSTEM
• Applicant: Clark Laboratories, Inc.
• Product Code: LSE · Microbiology
• Decision Date: Jul 22, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3235
• Device Class: Class 1

Intended Use

The Viral Capsid Antigen (VCA) IgM kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgM antibodies in human serum to VCA antigen. The Clark anti-VCA IgM assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgG, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis in the adult population.

Device Story

Device is an ELISA kit for qualitative detection of IgM antibodies to Epstein-Barr Viral Capsid Antigen (VCA) in human serum. Principle: affinity-purified gp125 VCA antigen attached to microtiter wells; patient serum added; if specific IgM present, it binds to antigen; unbound material washed away; enzyme-labeled anti-human IgM conjugate added; substrate solution added; color change measured photometrically. Used in clinical laboratories by trained personnel. Output is photometric measurement indicating presence of specific antibodies. Results used by clinicians alongside other EBV serologies to aid infectious mononucleosis diagnosis.

Clinical Evidence

Clinical evaluation performed on 166 serum samples characterized as seronegative, acute, or seropositive. Relative sensitivity for acute cases was 97.4% (95% CI: 92.2%-100%). Relative specificity was 96.4% (95% CI: 89.4%-100%) for seronegative and 99.0% (95% CI: 97.0%-100%) for seropositive samples. Relative agreement was 98.2%. Precision evaluated across three days at two sites; C.V. values ranged from 5.49% to 192.25% (high variance noted in negative controls). No cross-reactivity observed with HSV I & II, CMV, VZV, or rheumatoid factor.

Technological Characteristics

ELISA-based immunoassay. Solid phase: microtiter wells coated with affinity-purified gp125 VCA antigen. Detection: enzyme-labeled anti-human IgM conjugate and substrate solution. Measurement: photometric absorbance. Standalone diagnostic kit.

Indications for Use

Indicated for the qualitative determination of IgM antibodies to Epstein-Barr Viral Capsid Antigen in human serum to aid in the diagnosis of infectious mononucleosis in the adult population.

Regulatory Classification

Identification

Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).

Submission Summary (Full Text)

{0}------------------------------------------------

# 11980596

.

ﻣﻨﻬﺎ ﺑ

## JUL 22 1998

Summary of Safety and Effectiveness Information VCA IgM ELISA Test Kit

- I. Trinity Biotech US PO Box 1059 Jamestown, NY 14702-1059 Contact person: Ron Cruver Telephone: [phone] Date of preparation: Feb 11,1998
II. Description of Device

The Wampole Epstein-Barr Viral Capsid Antigen (VCA) IgM kit is an Enzyme-Linked Immunosorbent Assays (ELISA) for the qualitative determination of IgM antibodies in human serum to VCA antigen. The Wampole anti-VCA IgM assay may be used in conjunction with other Epstein-Barr serologies (VCA IgG, EBNA-1 IgG, EA-D IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis.

#### For In Vitro Diagnostic Use Only.

The VCA IgM ELISA test is an enzyme linked immunosorbent assay to detect IgM antibodies to Epstein-Barr Viral Capsid antigen. Afinity purified gp125 VCA antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgM is added to each well. If antibody is present it will bind to the antibody attached to the antigen on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.

#### III. Predicate Device

The VCA IgM ELISA test is substantially equivalent to EBV serology. Equivalence is demonstrated by the following comparative results:

{1}------------------------------------------------

#### Performance Characteristics

#### 1. Sensitivity and Specificity Based on Serum Characterization

One hundred and sixty six selected serum were tested at a clinical lab. The serum from the study were characterized as seronegative ( no serological evidence of past or present EBV infection), acute (VCA IgM and heterophile antibody present, EBNA IgG absent), or seropositive (presence of VCA IgG antibodies and EBNA IgG, no evidence of VCA IgM or heterophile antibody, indicative of past infection). The sensitivity, specificity and agreement of the assay was determined based on this characterization. It was assumed that the VCA IgM response should be negative for seronegative, and convalescent serum, and positive for acute serum. The results are summarized in Table 1.

#### Table 1

| | | Acute<br>VCA IgM+<br>EBNA IgG -<br>Heterophile + | Seropositive<br>VCA IgG+<br>EBNA IgG+<br>VCA IgM-<br>Heterophile - | Seronegative<br>VCA IgG-<br>EBNA IgG -<br>VCA IgM -<br>Heterophile - |
|--------------------|-----------|--------------------------------------------------|--------------------------------------------------------------------|----------------------------------------------------------------------|
| Wampole<br>VCA IgM | Positive | 37 | 1 | 1 |
| | Equivocal | 1 | 0 | 0 |
| | Negative | 1 | 98 | 27 |
| | Total | 39 | 99 | 28 |

| Relative Sensitivity (Acute) | = 37/38 = 97.4% | 95% Confidence Interval = 92.2%-100% |
|-------------------------------------|-------------------|--------------------------------------|
| Relative Specificity (Seronegative) | = 27/28 = 96.4% | 95% Confidence Interval = 89.4%-100% |
| Relative Specificity (Seropositive) | = 98/99 = 99.0% | 95% Confidence Interval = 97.0%-100% |
| Relative Agreement | = 162/165 = 98.2% | 95% Confidence Interval = 96.1%-100% |

Equivocal results were not included in the calculations.

Equivocal results were not retested. They were reported as equivocal.

The 95% confidence intervals were calculated using the normal method.

{2}------------------------------------------------

#### 2. Precision.

The Wampole VCA IgM EIA was evaluated for precision by testing six sera ten times each on three different days at two different sites. The results are summarized in the table below.

### Inter Site Precision Data

| Inter Site Precision (n=60) | | | |
|-----------------------------|------|-------|---------|
| Serum# | X | S.D. | C.V. |
| 1 | 1.55 | 0.230 | 14.87% |
| 2 | 1.55 | 0.172 | 11.11% |
| 3 | 4.61 | 0.491 | 10.67% |
| 4 | 3.09 | 0.389 | 12.59% |
| 5 | 0.35 | 0.215 | 62.22% |
| 6 | 0.04 | 0.039 | 94.67% |
| HPC* | 3.23 | 0.480 | 14.90% |
| CAL** | 2.00 | 0.110 | 5.49% |
| NC* | 0.01 | 0.016 | 192.25% |

X = Mean ISR Value

S.D. = Standard Deviation

C.V. = Coefficient of Variation

* HPC and NC n=6

** Cal n = 18

{3}------------------------------------------------

3. Cross-Reactivity. Sera containing IgM antibody detectable by ELISA to Herpes Simplex Virus I & II, Cytomegalovirus, and Varicella Zoster Virus were assayed. Sera containing rhuematoid factor (RF) were also assayed. The data summarized in Table 3 indicates that antibodies to Herpes Viruses and sera containing RF do not cross-react with the VCA IgM EIA kit.

| Specificity | VCA IgM | | Alternate Assay | |
|-------------|---------|---|-----------------|---|
| RF + | 0.04 | - | 1.87 | + |
| RF + | 0.03 | - | 1.82 | + |
| RF + | 0.01 | - | 1.73 | + |
| RF + | 0.01 | - | 1.80 | + |
| RF + | 0.02 | - | 1.85 | + |
| VZV M + | 0.33 | - | 3.28 | + |
| VZV M + | 0.10 | - | 5.46 | + |
| VZV M + | 0.04 | - | 4.98 | + |
| VZV M + | 0.08 | - | 2.34 | + |
| VZV M + | 0.03 | - | 2.18 | + |
| HSV 1 M + | 0.02 | - | 2.53 | + |
| HSV 1 M + | 0.02 | - | 1.65 | + |
| HSV 1 M + | 0.01 | - | 1.34 | + |
| HSV 1 M + | 0.01 | - | 1.32 | + |
| HSV 2 M + | 0.06 | - | 1.76 | + |
| HSV 2 M + | 0.05 | - | 1.60 | + |
| HSV 2 M + | 0.03 | - | 2.09 | + |
| HSV 2 M + | 0.04 | - | 1.96 | + |
| CMV M + | 0.07 | - | 1.23 | + |
| CMV M + | 0.04 | - | 1.92 | + |
| CMV M + | 0.04 | - | 3.83 | + |
| CMV M + | 0.06 | - | 1.32 | + |

{4}------------------------------------------------

Image /page/4/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA". The caduceus symbol is composed of three curved lines that converge at the bottom.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

· · ·

### JUL 22 1998

CLARK LABORATORIES, INC. c/o William L. Boteler, Jr. IMMUNO PROBE, INC. 1306 Bailes Lane, Suite F Frederick, MD 21701

Re: K980596 Trade Name: VCA IgM ELISA Requlatory Class: II Product Code: LSE Dated: April 22, 1998 Received: April 30, 1998

Dear Mr. Boteler:

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 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 requirement, 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 requlatory 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.

{5}------------------------------------------------

Paqe 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 Butman

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

{6}------------------------------------------------

Page 1 of 1

510(k) Number: K980596

Device Name: VCA IgM ELISA

Indications For Use: The Viral Capsid Antigen (VCA) IgM kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgM antibodies in human serum to VCA antigen. The Clark anti-VCA IgM assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgG, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis in the adult population.

### PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) 双 【【日】【:】【

Concurrence of CDRH, Office of Device Evaluation (ODE) Prescription Use V OR Over-The Counter Use (Per 21 CFR 801.109) (Optional Format 1-2-96)

Division of Clinical Laboratory Devices
510(k) Number K980596