SERAQUEST ANTI-THYROID PEROXIDASE (TPO)

K023593 · Quest Intl., Inc. · JZO · Feb 6, 2003 · Immunology

Device Facts

• Record ID: K023593
• Device Name: SERAQUEST ANTI-THYROID PEROXIDASE (TPO)
• Applicant: Quest Intl., Inc.
• Product Code: JZO · Immunology
• Decision Date: Feb 6, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5870
• Device Class: Class 2

Intended Use

The Anti-Thyroid Peroxidase test is intended for the quantative detection of human IgG antibodies to thyroid peroxidase antigen, in human serum by enzyme immunoassay. The presence of anti-thyroid peroxidase antibodies can be used with other serological tests and clinical findings to aid diagnosing individuals with Autoimmune Thyroditis and Grave's Disease. For In Vitro Diagnostic Use Only.

Device Story

SeraQuest Anti-Thyroid Peroxidase is a solid-phase enzyme immunoassay (EIA) for detecting IgG antibodies against thyroid peroxidase in human serum. The device uses microwells coated with purified human thyroid peroxidase antigen. Patient serum is incubated in the wells; if anti-TPO IgG antibodies are present, they bind to the antigen. After washing, an enzyme-labeled conjugate (goat anti-human IgG) is added, followed by a substrate (p-Nitrophenyl phosphate). The enzyme converts the substrate into a yellow end-product, measured photometrically at 405 nm. Results are reported in IU/mL based on a standard curve calibrated to NIBSC standards. The test is performed in a clinical laboratory setting by trained personnel. Results are used by clinicians in conjunction with other serological tests and clinical findings to assist in diagnosing Autoimmune Thyroiditis and Grave's disease.

Clinical Evidence

Clinical study compared SeraQuest Anti-Thyroid Peroxidase to the Pharmacia Varelisa TPO Antibodies test using 141 serum specimens. Results showed 22 positive, 107 negative, and 1 equivocal result in both assays. Excluding equivocal results, relative sensitivity was 100% (95% CI: 99.9-100%), relative specificity was 99.1% (95% CI: 97.7-100%), and overall agreement was 99.2% (95% CI: 97.3-100%). Discordant results were verified using a third device (Scimedix Anti-Thyroid Peroxidase Test).

Technological Characteristics

Solid-phase enzyme immunoassay (EIA) using polystyrene microwells. Antigen: purified human thyroid peroxidase. Conjugate: goat anti-human IgG labeled with alkaline phosphatase. Substrate: p-Nitrophenyl phosphate. Stop reagent: 0.5 M Trisodium phosphate. Readout: spectrophotometric at 405 nm (reference 620 nm). Normalization via standard curve. Reporting units: IU/mL.

Indications for Use

Indicated for the quantitative detection of IgG antibodies to thyroid peroxidase in human serum to aid in the diagnosis of Autoimmune Thyroiditis and Grave's disease. For in vitro diagnostic use.

Regulatory Classification

Identification

A thyroid autoantibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the thyroid autoantibodies (antibodies produced against the body's own tissues). Measurement of thyroid autoantibodies may aid in the diagnosis of certain thyroid disorders, such as Hashimoto's disease (chronic lymphocytic thyroiditis), nontoxic goiter (enlargement of thyroid gland), Grave's disease (enlargement of the thyroid gland with protrusion of the eyeballs), and cancer of the thyroid.

Predicate Devices

• Pharmacia Varelisa TPO Antibodies (K013488)

Reference Devices

• Scimedix Anti-Thyroid Peroxidase Test

Submission Summary (Full Text)

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#### KO23593 510(k) SUMMARY

| Applicant: | Quest International, Inc.<br>1938 N.E. 148th Terrace<br>North Miami, FL 33181 | FEB 06 2003 |
|------------------------|---------------------------------------------------------------------------------------------------------|-------------|
| Registration No. | 1061839 | |
| Contact Person: | Robert A. Cort, V.P., Quality Assurance | |
| Telephone: | [phone] | |
| Telefax: | [phone] | |
| Manufacturing Site: | Same as above | |
| Device: | SeraQuest® Anti-Thyroid Peroxidase | |
| Device Name: | Anti-Thyroid Peroxidase, Multiple autoantibodies immunological tes<br>system (21CFR § 866.5660)<br>5870 | |
| Device Classification: | Class II (Performance Standards) | |

### Description:

The SeraQuest Anti-Thyroid Peroxidase test is a solid-phase enzyme immunoassay (EIA), which is performed in microwells, at room temperature, in three thirty minutes incubations. It has been developed to detect IgG antibodies which are directed against Thyroid Peroxidase, in human serum.

The Calibrators in the SeraQuest Anti-Thyroid Peroxidase test kit have been assigned values based on the NIBSC standard. Test results are reported as international units per milliliter (IU/mL).

### Principle:

Diluted samples are incubated in wells coated with thyroid peroxidase antigen. Antibodies directed against this antigen (if present) are immobilized in the wells. Residual sample is eliminated by washing and draining, and conjugate (enzyme-labeled antibodies to human IgG) is added and incubated. If IgG antibodies to thyroglobulin antigen are present, the conjugate will be immobilized in the wells. Residual coniugate is eliminated by washing, and the enzyme substrate is added and incubated. In the presence of the enzyme, the substrate is converted to a yellow end-product which is read photometrically at 405 nm.

### Intended Use:

iended Use: The Anti-Thyroid Peroxidase test is intended for the quantative detection of human IgG antibodies to thyroid peroxidase antigen, in human serum by enzyme immunoassay. The presence of anti-thyroid peroxidase antibodies can be used with other serological tests and clinical findings to aid

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diagnosing individuals with Autoimmune Thyroditis and Grave's Disease. For In Vitro Diagnostic Use Only.

## Predicate Device:

The SeraQuest Anti-Thyroid Peroxidase test is substantially equivalent in intended use and performance, to the Pharmcia Varelisa TPO Antibodies, Freiburg, Germany.

## Summary of Technological Characteristics:

| Characteristic | SeraQuest<br>Anti-Thyroid Peroxidase<br>Test | Pharmacia<br>Varelisa<br>TPO Antibodies Test |
|--------------------------------------|-------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------|
| Description: | Enzyme Immunoassay | Enzyme Immunoassay |
| Intended Use: | The detection of IgG<br>antibodies against<br>thyroid peroxidase<br>in human serum. | The detection of IgG<br>antibodies against<br>thyroid peroxidase<br>in human serum. |
| Solid Phase: | Polystyrene Microwell | Polystyrene Microwell |
| Antigen: | Purified<br>thyroid peroxidase<br>(human thyroid) | Recombinant<br>thyroid peroxidase |
| Number of Incubation Periods: | Three | Three |
| Sample Dilution: | 1:51 | 1:101 |
| Sample Incubation<br>Duration: | 30 minutes | 30 minutes |
| Incubation Temperature: | Room temperature | Room temperature |
| Ezyme-labeled Conjugate: | | |
| Antibody | Goat anti-human IgG | Goat anti-human IgG |
| Enzyme | Alkaline phosphatase | Horse Radish Peroxidase |
| Conjugate Volume: | 100 μl | 100 μl |
| Conjugate Incubation<br>Duration: | 30 minutes | 30 minutes |
| Substrate: | p-Nitrophenyl<br>phosphate | TMB |
| Subtrate Volume: | 100 μl | 100 μl |
| Substrate Incubation<br>Duration: | 30 minutes | 10 minutes |
| Stop Reagent: | 0.5 M Trisodium<br>phosphate | 0.34 M<br>Sulfuric acid |
| Stop Reagent Volume: | 100 μl | 50 μl |
| Readout: | Spectrophotometric | Spectrophotometric |
| Wavelength:<br>Reference Wavelength: | 405 nm<br>620 nm | 450 nm |
| Normalization: | Standard Curve | Standard Curve |
| Reporting Unit: | IU / mL | IU / mL |

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APPENDIX 3.

Summary of Clinical Testing:

Experimental Procedure

To challenge the cutoff values, 141 serum specimens were tested at Quest International, Inc., concurrently by the SeraQuest Anti-Thyroid Peroxidase test, and the Varelisa TPO Antibodies test (Pharmacia & Upjohn). The assays were performed and interpreted according to the instructions in the manufacturer's package inserts.

### Results and Conclusion

The qualitative agreement between the SeraQuest and the Pharmacia tests is shown in Table 1.

Of the 141 specimens tested, 22 were positive, 107 were negative and 1 was equivocal in both the SeraQuest and Varclisa tests (please see Table C-3). Of the 11 specimens remaining, 1 specimen which was negative by the Varelisa test, was positive by the SeraQuest test; 1 specimen which was negative in the Serclivest test, was equivocal by the Varelisa test; 7 which were equivocal in the SeraQuest test, 2 vere positive and 5 negative in the Varelisa test; 2 which were equivocal in the Varelisa test were positive in the SeraQuest test.

Excluding the equiv cal results, the sensitivity of the SeraQuest Anti-Thyroid Peroxidase (TPO) test relative to the Varaint test was 100%, or 99.9% to 100% (95% C.I.); the specificity was 99.1%, or 97.7% to 100% (95% C.I.); respectively. The overall agreement was 99.2%, or 97.3% to 100% (95% C.I.) (please see Talla C-3).

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# ABLE 1.

# RESULTS OF SeraQuest ANTI-THYROGLOBULIN ASSAYS AND PHARMACIA ANTI-THYROGLOBULIN ASSAYS ON 141 SERUM SPECIMENS.

| | SeraQuest | | | | | |
|-----------|-----------|-----|-----|-----------------------|------|------------|
| PHARMACIA | POS | EQU | NEG | | % | 95% C.I.** |
| POS | 22 | 2 | 0 | Relative Sensitivity* | 100 | 99.9-100 |
| EQU | 2 | 1 | 1 | | | |
| NEG | 1 | 5 | 107 | Relative Specificity* | 99.1 | 97.7-100 |
| | | | | Overall Agreement* | 99.2 | 97.3-100 |

* Excluding equivocal results.

** 95%Confidence Interval calculated by the normal method.

The specimen that gave a discordant result was tested by a second legally marketed device, the Scimedix Anti-Thyroid Peroxidase Test, Scimedix Corp., Denville, New Jersey. The sample gave a ാsitive result with the Scimedix test.

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Image /page/4/Picture/1 description: The image shows a logo for the Department of Human Services USA. The logo consists of a circular border with the text "HUMAN SERVICES USA DEPARTMENT" arranged around it. Inside the circle is a stylized graphic of three human profiles facing to the right, stacked one behind the other, with flowing lines suggesting movement or connection.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 0 6 2003

Mr. Robert A. Cort Vice President, Quality Assurance Quest International, Inc. 1938 N.E. 148th Terrace North Miami, FL 33181

Re: k023593

Trade/Device Name: SeraQuest Anti Thyroid Peroxidase (TPO) Regulation Number: 21 CFR 866.5870 Regulation Name: Thyroid Autoantibody Immunological Test System Regulatory Class: Class II Product Code: JZO Dated: December 23, 2002 Received: December 24, 2002

Dear Mr. Cort:

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. Iisting 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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Page 2 –

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,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Quest International, Inc., 1938 N.E. 148th Terrace, N. Miami, FL 33181 Page No. . . - -

#### APPENDIX 6

Page

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: SeraQuest Anti-Thyroid Peroxidase (TPO)

Indications For Use:

- For the quantitative detection of IqG antibodies to thyroid peroxidase in human ﺎ . serum by enzyme immunoassay.
- The SeraQuest Anti-thyroid peroxidase test can be used with other serological 2. tests and clinical findings, to aid in the diagnosis of thyroid diseases such as Autoimmune Thyroiditis and Graves' disease.
- 3. For in vitro diagnostic use only.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

A. Plewes for S. Bautista

Division of Clinical Labora 510/k) Number

Prescription Use (Per 21 CFR 801.109)

OR

Over-The-Counter Use_

(Optional Format 1-2-96)