HEP-2000 COLORZYME ANA-RO TEST SYSTEM, MODEL 4200-RO

K983924 · Immuno Concepts, Inc. · DHN · Dec 18, 1998 · Immunology

Device Facts

• Record ID: K983924
• Device Name: HEP-2000 COLORZYME ANA-RO TEST SYSTEM, MODEL 4200-RO
• Applicant: Immuno Concepts, Inc.
• Product Code: DHN · Immunology
• Decision Date: Dec 18, 1998
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5100
• Device Class: Class 2

Intended Use

This test system is for in vitro diagnostic use for the detection of antinuclear antibodies in human serum, with specific identification of autoantibodies to the SS-A/Ro antigen. This test system is to be used as an aid in the detection of antibodies associated with systemic rheumatic disease. The results from this assay can be used as an aid in the diagnosis of autoimmune diseases.

Device Story

Indirect immunoenzyme antibody test; utilizes transfected HEp-2000 cell line overexpressing SS-A/Ro autoantigen. Input: human serum samples. Process: patient serum incubated with transfected cells; presence of anti-SS-A/Ro antibodies produces distinctive staining pattern. Output: visual identification of staining patterns via microscopy. Used in clinical laboratories; operated by trained laboratory personnel. Distinctive staining pattern serves as confirmation for anti-SS-A/Ro antibodies; aids clinicians in diagnosing systemic rheumatic/autoimmune diseases. Benefits: improved sensitivity for SS-A/Ro detection compared to non-transfected HEp-2 cells; higher titer values for anti-Ro/SS-A antibodies.

Clinical Evidence

Bench testing only. Evaluated 500 healthy donors, 46 patients with SLE/Sjögren's, and 230 patients with various rheumatic/non-rheumatic diseases. Compared HEp-2000 staining patterns against non-transfected HEp-2 cells, ELISA, and Western blot. HEp-2000 showed 100% sensitivity (46/46) for anti-SS-A/Ro positive samples. In a reference lab study (n=349), distinctive staining pattern showed 99.6% concordance with positive ELISA results. Reproducibility confirmed across three lots and multiple occasions.

Technological Characteristics

Indirect immunoenzyme antibody test; substrate is transfected HEp-2000 cell line overexpressing SS-A/Ro autoantigen. Principle: immunofluorescence/immunoenzyme staining. Form factor: microscope slides. Analysis: visual microscopic observation of staining patterns. No software or electronic components.

Indications for Use

Indicated for the semi-quantitative detection of antinuclear antibodies (ANA) in human serum and specific identification of autoantibodies to the SS-A/Ro antigen. Used as an aid in the diagnosis of systemic rheumatic and autoimmune diseases.

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

• RELISA® SS-A/SS-B Antibody Test System (K955603)

Submission Summary (Full Text)

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# DEC 1 8 1998

K983924

Image /page/0/Picture/2 description: The image shows the logo for Immuno Concepts. The logo consists of two horizontal lines on the left, followed by the letters "IC" with a stylized infinity symbol in the middle. To the right of the "IC" is the word "immuno" stacked on top of the word "concepts".

- 510(k) SUMMARY*

Date Prepared: August 10, 1998 Contact Person: Eric S. Hoy, Ph.D. Name of Device:

- · Trade Name HEp-2000® Colorzyme® ANA-Ro Test System
- · Common Name HEp-2000® Colorzyme® ANA-Ro Test System
- · Classification Name Antinuclear Antibody (21 CFR 866.5100)

Legally marketed device with which this device has been shown to be equivalent: RELISA® SS-A/SS-B Antibody Test System, K955603

### Description:

This is an indirect immunoenzyme antibody test for the semi-quantitative detection of antinuclear antibody in human serum. The transfected HEP-2 cell line allows for the identification of anti-SS-A/Ro antibodies because of the unique staining pattern that these antibodies show on this cell line.

### Intended Use:

This test system is for in vitro diagnostic use for the detection of antinuclear antibodies in human serum, with specific identification of autoantibodies to the SS-A/Ro antigen. This test system is to be used as an aid in the detection of antibodies associated with systemic rheumatic disease. The results from this assay can be used as an aid in the diagnosis of autoimmune diseases.

## Summary of Technological Characteristics Compared to the Predicate Device:

This device is an indirect immunoenzyme antibody test for the detection of antinuclear antibodies. This 510(k) submission is an extension of K950979. In this new submission we have shown that the transfected HEp-2000® cell line produces a distinctive pattern that is confirmatory for the presence of antibodies to the SS-A/Ro autoantigen. We have compared the present device to an ELISA assay which is confirmatory for antibodies to the SS-A/Ro autoantigen (K955603) .

## Description of Laboratory Data That Indicate Substantial Equivalence: NORMAL SAMPLES

Sera from 500 healthy blood donors, 242 females and 258 males, none of whom had any known history of rheumatic diseases, were tested in parallel using commercially available, non-transfected HEp-2 cells and the HEp-2000® Colorzyme® ANA-Ro Test System. In this population, 36 samples (7.2%) showed positive antinuclear antibody tests at a 1:40 dilution of serum. Patterns of staining were identical on the two substrates for 34 of the 36 positive samples. The two samples that showed differences were both from female patients, and both were confirmed to contain anti-SS-A/Ro antibodies. One of these samples showed a weak fine speckled reaction on the non-transfected HEO-2 cells and the typical "SS-A/Ro" staining on the HEp-2000® Colorzyme® ANA-Ro Test System. The other sample was negative on the non-transfected HEp-2 but showed typical "SS-A/Ro" staining on the HED-2000® Colorzyme® ANA

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Ro Test System. The SS-A/Ro specificity of these two samples was confirmed by ELISA testing and by Western immunoblotting. Samples which were negative on the ANA tests were also negative in the ELISA assay.

#### SERA FROM PATIENTS WITH ONLY RO/SS-A ANTIBODIES

Sera from 46 patients with SLE or Sjögren's Syndrome were tested using commercially available, non-transfected HEp-2 cells and the HEp-2000® Colorzyme® ANA-Ro Test System. All of these sera were confirmed to contain antibodies to the SS-A/Ro autoantigen by ELISA testing and by Western immunoblotting. No other autoantibodies were detected in any of these samples. Thirty six of these samples (78%) were positive (speckled pattern) with the non-transfected HEp-2 cells, and all 46 (100%) were positive (distinctive Ro/SS-A staining pattern) with the HEp-2000® Colorzyme® ANA-Ro Test System.

#### SERA FROM PATIENTS WITH AUTOANTIBODIES OTHER THAN SS-A/RO

Serum samples from 230 patients with a variety of rheumatic and non-rheumatic diseases were tested in parallel using commercially available, non-transfected HEp-2 cells and the HEp-2000® Colorzyme® ANA-Ro Test System. A single staining pattern was seen with 120 samples, and mixed patterns were seen with 110 samples. Among the total population of 230 samples, 333 staining patterns were identical on both substrates. Twenty nine samples showed the distinctive "SS-A/Ro" staining pattern on the HEp-2000® Test System. Twenty three of these samples showed speckled patterns on the non-transfected HEp-2 cells. The six discrepant samples (positive on HEp-2000®, but negative on nontransfected HEp-2 cells) all had SS-A/Ro antibodies, as demonstrated by the distinctive "SS-A/Ro" staining pattern, ELISA tests, and Western blot confirmation.

#### TITER COMPARISONS

Because of the overexpression of the SS-A/Ro autoantigen in the HEp-2000® cells, samples that contain anti-Ro/SS-A antibodies show higher titer values on these cells than the values obtained on non-transfected HEp-2 cells. Since none of the other autoantigens in the HEp-2000® cells are affected by the transfection process, sera with other autoantibody specificities do not show significant titer differences between the transfected HEp-2000® cell line and non-transfected HEp-2 cells.

#### REPRODUCIBILITY TITER

Ten samples, chosen from CDC controls and other well characterized in-house sera, were run on three different lot numbers of HEp-2000® slides, on three different occasions. In no case did a neqative sample show positive results. All titer values were within one two-fold dilution of the established mean titer value for all samples tested.

#### CONFIRMATION SS-A/Ro ANTIBODIES OF

In a large rheumatology reference laboratory, serum samples from 349 patients with known positive ANA tests were assayed using the HEp-2000® Colorzyme® In this selected population, 239 samples showed the distinctive Test System. SS-A/Ro staining pattern. Positive ELISA tests for SS-A/Ro antibodies were obtained in 238 (99.68) of these samples. An additional 79 samples showed strong speckled and/or homogeneous patterns, but gave positive ELISA tests for SS-A/Ro antibodies.. Thus, if the distinctive SS-A/Ro pattern is seen, it is confirmatory for the presence of SS-A/Ro antibodies, but the absence of the pattern does not rule out the possible presence of SS-A/Ro antibodies.

In the studies outlined above, we have examined a total of 429 sera that contain SS-A/Ro antibodies as confirmed by ELISA testing and/or Western

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Immunoblots, and which showed the distinctive SS-A/Ro staining pattern on the transfected HEp-2000® cell line. We have also seen samples which contain SS-A/Ro antibodies, but do not display the distinctive SS-A/Ro staining pattern, because high levels of other autoantibodies (usually anti-DNA antibodies or anti-Sm/RNP antibodies) mask the SS-A/Ro pattern. Thus, if the distinctive SS-A/Ro pattern is seen, it is confirmatory for the presence of SS-A/Ro antibodies, but the absence of the pattern does not rule out the possible presence of SS-A/Ro antibodies.

In accordance with 21 CFR 807.92(b)(3), we conclude from these data that the present device is substantially equivalent to the predicate device.

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## DEPARTMENT OF HEALTH & HUMAN SERVICES

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 1 8 1998 Eric S. Hoy, Ph.D., SI(ASCP) Chief Scientific Officer Immuno Concepts, Inc. 2280 Springlake Road, Suite 106 Dallas, Texas 75234

Re: K983924 HEP-2000® ANA-Ro Test System Trade Name: Regulatory Class: II Product Code: DHN Dated: November 3, 1998 November 4, 1998 Received:

Dear Dr. Hoy:

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 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). 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 Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, 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 Failure to comply with the GMP regulation may result in assumptions. regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Reqister. 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.

Image /page/3/Picture/8 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of three human profiles facing right, stacked on top of each other. The profiles are simple and abstract, with curved lines suggesting the faces. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the image.

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#### Page 2

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 requlation (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 [phone], or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

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 ..

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510(k) number (if known):

Device Name: HEp-2000® Colorzyme® ANA-Ro Test System

Indications for use:

This is an indirect immunoenzyme antibody test for the semi-quantitative detection of antinuclear antibodies in human serum, with specific identification of autoantibodies to the SS-A/Ro antigen. This test system is to be used as an aid in the detection of antibodies associated with systemic rheumatic disease.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Peter E. Malm

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K983924

Prescription Use
(Per 21 CFR 801.109) /

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

OR