VARELISA B2 GLYCOPROTEIN I ANTIBODIES SCREEN, MODELS 19048 AND 19096

K040452 · Pharmacia Deutschland GmbH · MSV · May 11, 2004 · Immunology

Device Facts

• Record ID: K040452
• Device Name: VARELISA B2 GLYCOPROTEIN I ANTIBODIES SCREEN, MODELS 19048 AND 19096
• Applicant: Pharmacia Deutschland GmbH
• Product Code: MSV · Immunology
• Decision Date: May 11, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5660
• Device Class: Class 2

Intended Use

The Varelisa B2-Glycoprotein I Antibodies Screen Kit is designed for the qualitative determination of β2-glycoprotein I antibodies in serum or plasma. The presence of B2-glycoprotein I antibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of thrombotic disorders related to the primary Antiphospholipid Syndrome or occurring secondary to systemic lupus erythematosis (SLE) or other autoimmune diseases.

Device Story

Varelisa B2-Glycoprotein I Antibodies Screen Kit is an ELISA-based diagnostic test; utilizes microplate wells coated with purified human β2-glycoprotein I antigen. Patient serum or plasma samples are applied; specific antibodies bind to antigen; detected via enzyme-labeled secondary antibody conjugate (horseradish peroxidase). Enzyme substrate added; color formation rate proportional to antibody concentration. Results reported as ratio of sample OD to cut-off OD. Used in clinical laboratories; performed by trained technicians. Output aids clinicians in diagnosing thrombotic disorders associated with Antiphospholipid Syndrome or SLE. Benefits include standardized qualitative assessment of autoimmune markers to support clinical decision-making.

Clinical Evidence

Bench testing only. Precision/reproducibility evaluated across 5 runs with 4 replicates per run; variances met specifications (within <12%, between <10%, total <15%). Analytical specificity tested against bilirubin, hemoglobin, chyle, and rheumatoid factor; no significant interference observed. Cut-off established using 432 healthy donors. Method comparison with predicate (n=40) showed 92.5% qualitative agreement. Matrix comparison (serum, citrate, heparin, EDTA plasma) showed no significant differences.

Technological Characteristics

Indirect noncompetitive enzyme immunoassay. Components: microplate strips coated with human purified B2-glycoprotein I, calibrator, negative control, enzyme-labeled conjugate, substrate, stop solution, buffered diluent, wash buffer. Detection principle: colorimetric enzyme-linked reaction. Sample type: serum or plasma.

Indications for Use

Indicated for qualitative detection of B2-Glycoprotein I antibodies (IgG/IgM/IgA) in human serum or plasma to aid in diagnosis of thrombotic disorders associated with primary Antiphospholipid Syndrome, systemic lupus erythematosus (SLE), or other autoimmune diseases.

Regulatory Classification

Identification

A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).

Predicate Devices

• INOVA QUANTA Lite™ B2 GPI Screen

Submission Summary (Full Text)

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#### ழ். 510(K) SUMMARY OF SAFETY AND EFFECTIVENESS

This summary of safety and effectiveness information is being submitted in accordance with the requirements of The Safety Medical Devices Act of 1990 (SMDA 1990) and 21 CFR Part 807.92.

| Assigned 510(k) Number: | K040452 |
|------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Date of Summary Preparation: | February 12, 2004 |
| Manufacturer: | Pharmacia Deutschland GmbH,<br>Diagnostics Division<br>Munzinger Strasse 7<br>D-79111 Freiburg, Germany |
| Company Contact Person: | Michael Linss<br>Manager, Regulatory Affairs<br>Pharmacia Deutschland GmbH<br>Diagnostics Division<br>Munzinger Strasse 7<br>D-79111 Freiburg, Germany<br>[phone](Phone)<br>[phone] (Fax) |
| Device Name: | Varelisa® B2-Glycoprotein I Antibodies Screen |
| Common Name: | B2-Glycoprotein I autoantibody<br>immunological test system |

Classification

| Product Name | Product Code | Class | CFR |
|--------------|--------------|-------|-----|
|--------------|--------------|-------|-----|

Varelisa® ß2-Glycoprotein I MSV ロ 866.5660 Antibodies Screen

## Substantial Equivalence to

INOVA QUANTA Lite™ B2 GPI Screen

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## Intended Use Statement

The Varelisa B .- Glycoprotein I Antibodies Screen EIA kit is designed for the qualitative determination of B2-Glycoprotein I antibodies in human serum or plasma.

The presence of B2-glycoprotein I antibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of thrombotic disorders related to the primary Antiphospholipid Syndrome or occurring secondary to systemic lupus erythematosus (SLE) or other autoimmune diseases.

## General Description of the Device

The Varelisa ß2-Glycoprotein I Antibodies Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of antibodies against ß glycoprotein I in serum or plasma.

The test kit contains microplate strips coated with human purified ß2glycoprotein I. calibrator, negative control, enzyme-labeled conjugate, substrate and substrate stop solution, buffered diluent and wash buffer.

## Varelisa® ß2-Glycoprotein I Antibodies Screen Test Principle

Varelisa B2-Glycoprotein I Antibodies Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of B2-glycoprotein I (IgG/IgM/IgA) antibodies in human serum or plasma. The wells of a microplate are coated with B2-glycoprotein I. Antibodies specific for B2-glycoprotein I present in the patient sample bind to the antigen.

In a second step the enzyme labeled second antibody (conjugate) binds to the antigen-antibody complex which leads to the formation of an enzyme labeled conjugate-antibody-antigen complex. The enzyme labeled antigen-antibody complex converts the added substrate to form a colored solution.

The rate of color formation from the chromogen is a function of the amount of conjugate complexed with the bound antibody and thus is proportional to the initial concentration of the respective antibodies in the patient sample.

### Device Comparison

INOVA QUANTA Lite™ ß2 GPI Screen (the predicate device) and PHARMACIA Varelisa B2-glycoprotein I Antibodies Screen (the new device) both are indirect noncompetitive enzyme immunoassays for qualitative detection of IgM, IgG and IgA antibodies against B2-glycoprotein I in serum. Both assays recommend the same sample dilutions and use comparable enzyme-linked conjugates and antigens.

Based on currently available data from the literature the measuring of the antibodies against ß2-glycoprotein I not only provides aid in the diagnosis of thrombotic disorders secondary to systemic lupus erythematosus or other autoimmune diseases, but also aids in the diagnosis of the primary

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antiphospholipid syndrome. Thus the intended use of Varelisa ß2-glycoprotein I Antibodies Screen was adapted to the current state of scientific knowledge. The corresponding literature is cited in the directions for use.

A difference between both assays is that the INOVA QUANTA Lite™ B2 GPI Screen is only recommended for use in serum specimen while the PHARMACIA Varelisa B2-glycoprotein I Antibodies Screen is outlined for use with serum and plasma. Corresponding performance data underline the effectiveness of the assay with plasma as sample. Minor differences between both assays are restricted to contents of buffers and stop solution. The INOVA QUANTA Lite™ B2 GPI Screen contains an additional assay control and the assay is evaluated by using the decision point method. PHARMACIA Varelisa B2-glycoprotein I Antibodies Screen assay uses an ODcut-off. Corresponding performance data show the comparability of the results.

## Laboratory equivalence

The comparability of INOVA QUANTA Lite™ ß2 GPI Screen and PHARMACIA Varelisa ß2-glycoprotein I Antibodies Screen is supported by a data set including

- · results obtained within a comparison study analyzing positive, equivocal and negative sera.
- results obtained for externally defined Calibrators. .
- · results obtained for samples from apparently healthy subjects (normal population).

The data show that the assay performs as expected from the medical literature. Furthermore the performance data show that the device is suitable for serum and plasma samples.

In summary, all available data support that the new device, PHARMACIA Varelisa B2-glycoprotein I Antibodies Screen Assay is substantially equivalent to the predicate device, INOVA QUANTA Lite™ ß2 GP1 Screen Assay, and that the new device performs according to state-of-the-art expectations.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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 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, resembling a bird-like shape.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 11 2004

Michael Linss, Ph.D. Manager, Compliance & Quality Pharmacia Deutschland GMBH Diagnostics Division Munzinger Strasse 7 Freiburg. Germany D-79111

Re: k040452

Trade/Device Name: Varelisa® ß2 Glycoprotein I Antibodies Screen Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MSV Dated: April 27, 2004 Received: April 30, 2004

Dear Dr. Linss:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Joseph L. Hackett

Joseph L. Hackett, Ph.D. Acting Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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# Varelisa® ß2-Glycoprotein I Antibodies Screen – New Device 510(k) Submission Section 1. Indications for Use Statement

510(k) Number:

K040452

Device Name: Varelisa® ß2-Glycoprotein I Antibodies Screen

### Intended Use Statement

The Varelisa 32-Glycoprotein I Antibodies Screen EIA kit is designed for the qualitative determination of \$2-Glycoprotein I antibodies in human serum or plasma. The presence of B2-glycoprotein I antibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of thrombotic disorders related to the primary Antiphospholipid Syndrome or occurring secondary to systemic lupus erythematosus (SLE) or other autoimmune diseases.

Thana Chan

ion Sign-C

Office of In Vitro Diagnostic Device Evaluation and Safety

510(K) K040452

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use

OR

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

(Per 21 CFR 801.109)