INDIRECT FLUORESCENCE ASSAY FOR ANTI-NATIVE DNA IGG ANTIBODY

K990916 · Stellar Bio Systems, Inc. · KTL · Apr 21, 1999 · Immunology

Device Facts

• Record ID: K990916
• Device Name: INDIRECT FLUORESCENCE ASSAY FOR ANTI-NATIVE DNA IGG ANTIBODY
• Applicant: Stellar Bio Systems, Inc.
• Product Code: KTL · Immunology
• Decision Date: Apr 21, 1999
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5100
• Device Class: Class 2

Intended Use

The Stellar Bio Systems' Indirect Fluorescence Assay (IFA) for Anti-native DNA (nDNA) IgG Antibody is intended for the qualitative and semi-quantitative detection of IgG (Immunoglobulin G) antibody to nDNA in human serum. Detection of nDNA IgG antibody in humans can be used as an aid in the diagnosis of systemic lupus erythematosus (SLE).

Device Story

The nDNA IgG IFA is an in vitro diagnostic test for human serum samples. The procedure involves incubating diluted patient serum on glass microscope slides containing fixed nDNA antigens; specific antibodies form antigen/antibody complexes. After washing, fluorescein-conjugated goat anti-human IgG is applied. Following a second incubation and wash, slides are examined via fluorescence microscopy. A positive result is indicated by bright green fluorescence at antigen sites. The device is intended for use by laboratory professionals to assist in SLE diagnosis. Clinical utility is limited to an aid in diagnosis; results are not intended to correlate directly with disease presence or absence.

Clinical Evidence

Bench testing only. Retrospective study of 149 human serum samples compared the Stellar nDNA IFA to a commercially available IFA. Results: 96.2% relative sensitivity (95% CI: 80.4% - 99.9%), 99.2% relative specificity (95% CI: 95.6% - 100%), and 98.7% relative agreement. Titer agreement study (n=20) showed 11/20 identical titers and 18/20 within ± one two-fold dilution. Reproducibility study (n=36) showed 31/36 identical titers and 5/36 within ± one two-fold dilution.

Technological Characteristics

Indirect fluorescence assay (IFA) using fixed nDNA antigens on glass microscope slides. Detection via fluorescein-conjugated goat anti-human IgG. Manual visual interpretation using fluorescence microscopy. No electronic or software components.

Indications for Use

Indicated for qualitative and semi-quantitative detection of IgG antibodies to nDNA in human serum as an aid in the diagnosis of systemic lupus erythematosus (SLE).

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

• Jus DNA IFA

Submission Summary (Full Text)

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4/21/99

K99 0916

# 510k Summary of Safety and Effectiveness

. nis summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is:

### Applicant Information:

| Date Prepared: | March 12, 1999 |
|-----------------|------------------------------------------|
| Name: | Stellar Bio Systems, Inc |
| Address: | 9075 Guilford Road<br>Columbia, MD 21046 |
| Contact Person: | John Brewer |
| PhoneNumber. | 410-381-8550 |
| Fax Number. | 410-381-8984 |

#### Device Information:

| Trade Name: | Indirect Fluorescence Assay for Anti-native DNA (nDNA) IgG Antibody |
|----------------------|---------------------------------------------------------------------|
| Common Name: | nDNA IgG IFA Test |
| Classification Name: | nDNA IgG Serological Reagent |

uivalent Device: _Jus DNA IFA

Device Description: The nDNA IgG IFA is an Indirect Fluorescence Assay (IFA) for the detection of IgG antibodies to nDNA antigen in human serum.

Intended Use: The Stellar Bio Systems' Indirect Fluorescence Assay (IFA) for Anti-native DNA (nDNA) IgG Antibody is intended for the qualitative and semi-quantitative detection of IgG (Immunoglobulin G) antibody to nDNA in human serum. Detection of nDNA IgG antibody in humans can be used as an aid in the diagnosis of systemic lupus erythematosus (SLE).

#### Principle of Procedure:

Stellar Bio Systems' fluorescent antibody assays use the indirect method of antibody detection and titer determination. Diluted patient serum sampled to fixed antigens provided on paint delineated wells on glass microscope slides. During a 30 minute incubation, antibody specific for nDNA antigens forms an antigen/antibody complex with the fixed antigens. In a brief washing step, nonspecific antibody and other unreacted serum proteins are eliminated. Fluorescein-conjugated goat anti-human IgG is then applied to the wells of the glass slide. The anti-IgG conjugate combines with human IgG, if present, during a 30 minute incubation. After a brief wash to remove unreacted conjugate, the slides are viewed by fluorescence microssopy. A positive antibody reaction is denoted by bright green fluorescence at the antigen sites.

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## Performance Characteristics

1. Relative Sensitivity and Specificity - The Stellar nDNA IFA kit was evaluated 1. Actative to a commercially available nDNA IFA. The samples were frozen retrospective relative to a volumerelany arants diagnosed with SLE. Ninety-nine sera were from sora. They bera work were gender, and geographical areas. The data in Table 1 summarizes the data.

| Table 1 |
|------------------------------------------------------------------------------|
| Relative Sensitivity and Specificity of the Stellar nDNA IFA Kit Relative to |
| Alternate IFA |

Stellar nDNA IFA

| | | Positive | Negative | Total |
|------------------------------------------|----------|-----------------|------------------------------------------|-------|
| | | Stellar INSTANT | | |
| Alternate<br>IFA | Positive | 25 | 1 | 26 |
| | Negative | 1 | 122 | 123 |
| | Total | 26 | 123 | 149 |
| Relative Sensitivity = $25/26 = 96.2%$ | | | 95% Confidence Interval<br>80.4% - 99.9% | |
| Relative Specificity = $122/123 = 99.2%$ | | | 95.6% - 100% | |
| Relative Agreement = $147/149 = 98.7%$ | | | 95.2% - 99.8% | |

Please be advised that 'relative' refers to the comparison of this assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison assay's accuracy to predict disease.

- 2. Titer Agreement: 20 positive sera were serially two-fold diluted and the endpoint titer was determined on the Stellar nDNA IFA and a commercially available nDNA IFA. The endpoint titer results are as follows.

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| Identical Titer | 11/20 |
|-------------------------------|-------|
| $\pm$ one, two-fold dilution | 7/20 |
| $\pm$ two, two-fold dilutions | 2/20 |

3. Reproducibility: Three positive with various titers (1:20, 1:160, 1:640) and one negative sera were serially diluted and assayed three times each on three different assays. 31/36 of the end point titers were identical. 5/36 of the end point titers were within ± one, two-fold dilution.

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APR 2 1 1999

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Mr. John Brewer Stellar Bio Systems, Inc. 9075 Guilford Road Columbia, Maryland 21046

Re: K990916

> Trade Name: Indirect Fluorescence Assay for Anti-native DNA (nDNA) IgG Antibody Regulatory Class: II Product Code: KTL Dated: March 12, 1999 Received: March 18, 1999

Dear Mr. Brewer:

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 Regulations, 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 OS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory 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.

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

Sincerely vours.

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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Page 1 of 1

#### K990916 510(k) Number: Not Known

Device Name: Indirect Fluorescence Assay (IFA) for Anti-native DNA (nDNA) IgG Antibody

Indications For Use: The Stellar Bio Systems' Indirect Fluorescence Assay (IFA) for Anti-native DNA (nDNA) IgG Antibody is intended for the qualitative and semi-quantitative detection of IgG (Immunoglobulin G) antibody to nDNA in human serum. Detection of nDNA IgG antibody in humans can be used as an aid in the diagnosis of systemic lupus erythematosus (SLE).

Peter E. Maher

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use V (Per 21 CFR 801.109)

OR

Over-The Counter Use (Optional Format 1-2-96)