VARELISA RECOMBI CTD SCREEN, MODEL 13096

K050967 · Sweden Diagnostics (Germany) GmbH · LJM · Jun 28, 2005 · Immunology

Device Facts

• Record ID: K050967
• Device Name: VARELISA RECOMBI CTD SCREEN, MODEL 13096
• Applicant: Sweden Diagnostics (Germany) GmbH
• Product Code: LJM · Immunology
• Decision Date: Jun 28, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5100
• Device Class: Class 2

Intended Use

The Varelisa ReCombi CTD Screen EIA kit is for qualitative determination of 10 antinuclear antibodies in human serum or plasma to aid in the diagnosis of systemic rheumatic diseases such as SLE (systemic lupus erythematosus), drug induced lupus, scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjogren’s syndrome) and Polymyositis/dermatomyositis. The Varelisa ReCombi CTD Screen detects antibodies against dsDNA, RNP, (RNP 70, A, C), Sm (B, B', D) SS-A/Ro (52 kDa, 60 kDa), SS-B/La, Scl-70, CENP-B, Histone, Ribosomal P protein and Jo-1 in a single microwell.

Device Story

ELISA-based diagnostic test; detects ten specific antinuclear antibodies in human serum or plasma. Microtiter plate wells coated with recombinant and native purified nuclear antigens and dsDNA. Patient sample added; specific antibodies bind to immobilized antigens. Rabbit anti-human IgG HRP conjugate added; forms enzyme-labeled conjugate-antibody-antigen complex. TMB substrate added; color formation proportional to antibody concentration. Performed in clinical laboratories by trained personnel. Requires microplate reader (450 nm/620 nm). Results aid clinicians in diagnosing systemic rheumatic diseases. Benefits include simultaneous screening for multiple autoantibodies in a single microwell.

Clinical Evidence

Clinical comparison study using 183 CTD samples and 100 disease controls. Positive agreement for CTD samples was 87.4% (95% CI: 81.7-91.9%) vs 85.2% (95% CI: 79.3-90.0%) for predicate. Negative agreement for control samples was 79.0% (95% CI: 69.7-86.5%) vs 84.0% (95% CI: 75.3-90.6%) for predicate. Data supports substantial equivalence.

Technological Characteristics

Indirect non-competitive EIA. Microtiter plate coated with recombinant/native nuclear antigens and dsDNA. Energy source: microtiter plate photometer (SLT Spectra II). Detection: HRP-conjugated anti-human IgG, TMB substrate. Qualitative output via OD ratio. Reagents: calibrator, positive/negative controls, wash buffer, sample diluent, stop solution.

Indications for Use

Indicated for qualitative determination of ten antinuclear antibodies in human serum or plasma to aid diagnosis of systemic rheumatic diseases including SLE, drug-induced lupus, scleroderma, MCTD, Sjögren's syndrome, and polymyositis/dermatomyositis. Prescription use only.

Regulatory Classification

Identification

An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).

Predicate Devices

• Varelisa® ReCombi ANA Screen (K993108)

Submission Summary (Full Text)

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#### 510(K) SUMMARY OF SAFETY AND 9. 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: | K050967 |
|------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Date of Summary Preparation: | June 15, 2005 |
| Manufacturer: | Sweden Diagnostics (Germany) GmbH<br>Munzinger Strasse 7<br>D-79111 Freiburg, Germany |
| Company Contact Person: | Michael Linss<br>Manager, Compliance & Quality<br>Sweden Diagnostics (Germany) GmbH<br>Munzinger Strasse 7<br>D-79111 Freiburg, Germany<br>[phone] (Phone)<br>[phone] (Fax) |
| Device Name: | Varelisa ReCombi CTD Screen |
| Common Name: | Antinuclear antibody<br>immunological test system |

#### Classification

| Product Name | Product Code | Class | CFR |
|------------------------------|--------------|-------|----------|
| Varelisa® ReCombi CTD Screen | LJM | II | 866.5100 |

### Substantial Equivalence to

Varelisa® ReCombi ANA Screen (510(k) number: K993108)

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## Intended Use Statement of the New Device

Intended use/Indication for use

The Varelisa ReCombi CTD Screen EIA kit is designed for the qualitative determination of ten antinuclear antibodies in human serum or plasma to aid in the diagnosis of systemic rheumatic diseases such as SLE (systemic lupus erythematosus), drug-induced lupus, scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/dermatomyositis. The Varelisa ReCombi CTD Screen detects antibodies against dsDNA, RNP (RNP70,A,C), Sm (B,B',D), SS-A/Ro(52 kDa,60 kDa), SS-B/La, Scl-70, CENP-B, Histone, Ribosomal P Protein and Jo-1 in a single microwell.

### Special condition for use statement

The device is for prescription use only.

#### Special instrument requirements

A microplate reader capable of measuring OD at 450 mm and 620 mm is required.

### General Description of the New Device

The new device is an enzyme-linked immunosorbent assay (ELISA) using microtiter plates as the solid phase. The plate wells are coated with antinuclear antigens, which allow anti-nuclear antibodies (sample) to react with the immobilized antigens. The conjugate is rabbit anti-human IgG horseradish peroxidase (HRP), which uses 3, 3'5, 5' tetramethylbenzidine dihydrochloride (TMB) as substrate. The kit contains calibrator and negative control. The kit also contains sample diluent, wash buffer concentrate and stop solution.

### Test Principle of the New Device

Varelisa ReCombi CTD Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of 10 antinuclear antibodies in serum or plasma. The wells of a microplate are coated with human recombinant and native purified nuclear antigens and dsDNA. Antibodies specific for the nuclear antigens present in a patient sample bind to these nuclear antigens.

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.

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### Device Comparison

The new device is developed as successor of the predicate device. Both assays the now assay principle and indications for use. They are indirect share the bains asseme immunoassays for qualitative determination of IgG antibodies against antinuclear antigens in serum and plasma. Both assays antioodies "agains" annote dilutions and use identical reagents (including the coolimions the bande to the relevant scientific literature both assays state in the Intended Use, that the measuring of antinuclear antibodies aids in the diagnosis of Connective Tissue Diseases such as SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/ dermatomyositis.

Differences do exist but do not affect the tenor of the "Intended Use" and do not Differences as entor Safety and Effectiveness" questions. The new device uses two additional antigens (Histone, Rib-P) and a synthetic peptide derived from the human SmD protein plus recombinant SmBB' instead of Sm antigen purified from calf thymus (complex consisting of SmBB' and SmD). Minor differences pertain to increased volumina of the reagents and leaving out the prewashing step of the antigen strips. The Wash buffer does no longer contain NaN3 and the substrate TMB is of lower concentration because the substrate incubation step is increased to 30 min.

### Laboratory equivalence

The comparability of predicate device and new device is supported by a data set including

- results obtained for clinically defined sera and for international . reference sera.
- results obtained for samples from apparently healthy subjects . (normal population).
- results obtained within a comparison study analyzing 100 . disease controls and 183 CTD samples.

Analysis of Agreement between individual test results and clinical definitions of samples.

| | Varelisa ReCombi CTD Screen | | Predicate Device | | Difference between<br>assays (%) | |
|----------------------------------|-----------------------------|---------------------------------|------------------|-----------------|---------------------------------------------------|------------------|
| | Agreement<br>(%) | 95% Confidence<br>Interval (CI) | Agreement<br>(%) | 95% CI | Varelisa ReC. CTD<br>Screen -<br>Predicate Device | 95% CI |
| Positive<br>(CTD<br>samples) | 87.4 | 81.7 - 91.9% | 85.2 | 79.3 -<br>90.0% | 2.2 | -1.7 -<br>5.0% |
| Negative<br>(Control<br>samples) | 79.0 | 69.7 - 86.5% | 84.0 | 75.3 -<br>90.6% | - 5.0 | -11.8 -<br>-0.2% |

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In summary, all available data support that the new device is substantially equivalent to the predicate device and that the new device performs according to state-of-the-art expectations.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administratio 2098 Gaither Road Rockville MD 20850

JUN 2 8 2005

Mr. Michael Linss Manager, Compliance and Quality Sweden Diagnostics (Germany) GmbH Munzinger Strasse 7 D-79111 Freiburg, Germany

k050967 Re:

Trade/Device Name: Varelisa ReCombi CTD Screen Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LJM Dated: April 15, 2005 Received: April 18, 2005

Dear Mr. 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). 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.

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Page 2 -

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/industry/support/index.html

Sincerely yours,

Robert Beckerh

Robert L. Becker, Jr., MD, P& 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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# Indications for Use

510(k) Number:

Device Name:

K050967

Varelisa ReCombi CTD Screen

#### Indications For Use:

The Varelisa ReCombi CTD Screen EIA kit is designed for the qualitative determination of ten antinuclear antibodies in human serum or plasma to addinathe diagnosis of systemic rheumatic diseases such as SLE (systemic ipus erythematosus), drug-induced lupus, scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polynysitis/ dermatomyositis. The Varelisa ReCombi CTD Screen detects antibodies against dsDNA, RNP (RNP70,A,C), Sm (B,B',D), SS-A/Ro(52 kDa,60 kDa), SS-B/La, Scl-70, CENP-B, Histone, Ribosomal P Protein and Jo-1 in a single miorovell.

Prescription Use V (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Mani Chow

**Division Sign-Off**

Office of In Vitro Dia Device Evaluation and

510(k) Ks50967