VARELISA TPO ANTIBODIES, MODEL 12348/12396

K993585 · Pharmacia & Upjohn Co. · JZO · Jan 5, 2000 · Immunology

Device Facts

• Record ID: K993585
• Device Name: VARELISA TPO ANTIBODIES, MODEL 12348/12396
• Applicant: Pharmacia & Upjohn Co.
• Product Code: JZO · Immunology
• Decision Date: Jan 5, 2000
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5870
• Device Class: Class 2

Intended Use

The Varelisa TPO Antibodies EIA kit is designed for the quantitative and qualitative determination of TPO (thyroid peroxidase) antibodies in serum or plasma to aid in the diagnosis of thyroid diseases such as Autoimmune Thyroiditis and Graves' Disease.

Device Story

Varelisa TPO Antibodies is an indirect noncompetitive enzyme immunoassay (EIA) for detecting TPO antibodies in patient serum or plasma. Microplate wells are coated with human recombinant TPO antigen; patient samples are added, allowing specific TPO antibodies to bind. An enzyme-labeled conjugate is added, forming an antigen-antibody sandwich complex. A substrate is introduced, resulting in color formation proportional to the concentration of TPO antibodies in the sample. The assay is performed in a clinical laboratory setting. Results assist clinicians in diagnosing autoimmune thyroid conditions. The device benefits patients by providing a standardized, specific diagnostic tool for thyroid disease management.

Clinical Evidence

Correlation study comparing subject device to predicate using 183 positive and negative samples. Results showed Pearson's correlation coefficient of 0.95 (R=0.90). Overall agreement was 98.9% after excluding equivocal samples. Evaluation of 39 blood donor samples yielded mean values of 0.4 IU/mL.

Technological Characteristics

Indirect noncompetitive enzyme immunoassay. Microplate wells coated with human recombinant TPO antigen. Detection via enzyme-labeled conjugate and chromogenic substrate. Standardized against NIBSC Research Standard 66/387. No software or electronic components described.

Indications for Use

Indicated for quantitative and qualitative determination of TPO antibodies in serum or plasma to aid diagnosis of thyroid diseases, including Autoimmune Thyroiditis and Graves' Disease.

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

• elias™ TM Antibodies

Submission Summary (Full Text)

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# Varelisa® TPO Antibodies - Device Modification 510(k) Submission Section 1. Indications For Use Statement

で

K993585 510(k) Number:

Device Name: Varelisa® TPO Antibodies

The Varelisa TPO Antibodies EIA kit is designed for the quantitative and qualitative determination of TPO (thyroid peroxidase) antibodies in serum or plasma to aid in the diagnosis of thyroid diseases such as Autoimmune Thyroiditis and Graves' Disease.

Peter E. Martin

Person Sign-Off

A Chineal Laboratory Devices 5 : chry invinber _

1

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use

OR

Over-The-Counter Use_

(Per 21 CFR 801.109)

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#### 510(K) SUMMARY OF SAFETY AND EFFECTIVENESS 9.

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: | 15993585 |
|------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Date of Summary Preparation: | October 11, 1999 |
| Distributor: | Pharmacia & Upjohn<br>Diagnostics Division, US Operation<br>7425-248-1<br>7000 Portage Road<br>Kalamazoo, MI 49001 |
| Manufacturer: | Pharmacia & Upjohn Diagnostics GmbH Co. KG<br>Munzingerstrasse 7<br>D-79111 Freiburg, Germany |
| Company Contact Person: | Karen E. Matis<br>Manager, Regulatory Affairs and Quality<br>Management<br>Diagnostics Division, US Operation<br>7000 Portage Road<br>7425-248-01<br>Kalamazoo, MI 49001<br>[phone] (Phone)<br>[phone] (Fax) |
| Device Name: | Varelisa® TPO Antibodies |
| Common Name: | Thyroid autoantibody immunological test<br>system. |
| Classification: | |

| Product Name | Product Code | Class | CFR |
|--------------------------|--------------|-------|----------|
| Varelisa® TPO Antibodies | 82JZO | II | 866.5870 |

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## Substantial Equivalence to:

elias™ TM Antibodies

## Indications For Use Statement:

The Varelisa TPO Antibodies EIA kit is designed for the quantitative and qualitative determination of TPO (thyroid peroxidase) antibodies in serum or plasma to aid in the diagnosis of thyroid diseases such as Autoimmune Thyroiditis and Graves' Disease.

## General Description of the Device

The Varelisa TPO Antibodies assay is an indirect noncompetitive enzyme immunoassay for the quantitative and qualitative determination of TPO (thyroid peroxidase) antibodies in serum or plasma.

The determination of TPO antibodies is of central importance for the clinical diagnosis of thyroid diseases. The presence of TPO antibodies suggests the possibility of autoimmune diseases such as Autoimmune Thyroiditis and Graves' Disease.

#### Varelisa® TPO Antibodies Test Principle

Varelisa TPO Antibodies is an indirect noncompetitive enzyme immunoassay. The wells of a microplate are coated with human recombinant TPO antigen. Antibodies specific for TPO present in a patient sample bind to this antigen.

In a second step an enzyme labeled second antibody (Conjugate) binds to the antigenantibody complex which leads to the formation of an enzyme labeled antigen-antibody sandwich 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:

elias TMAb Assay (the predicate/ original device) and Varelisa® TPO Antibodies Assay (the new/ modified device) are both indirect noncompetitive enzyme immunoassays for the determination of anti-thyroid antibodies in serum or plasma to aid in the diagmosis of thyroid diseases such as autoimmune thyroiditis and Grave's Disease.

The essential difference between both assays is the use of human recombinant TPO (new device) instead of the purified thyroid microsomal antigen (predicate device). This modification was initiated due to the fact that Thyroid Peroxidase is the accepted arget of the "thyroid microsomal" antibodies". In addition, the recombinant protein technology assures an antigen preparation free from contamination with Thyroglobulin.

An important common feature between the predicate and modified assays is the standardization against the Anti-Thyroid Microsome Serum, NIBSC Research Standard 66/387, assuring comparability of the assay results.

In a correlation study, a high degree of similarity was demonstrated: comparing 183 positive and negative samples, an R-value of 0.90 (Pearson's coefficient of correlation: 0.95) was obtained. Slight differences in the values are due to the different anigen sources (recombinant TPO antigen and microsome preparation, respectively). Onititing 7 samples (out of 183 samples) which were found equivocal in Varelisa TPO Antibodies (for elias TM Abs no equivocal range is defined), the overall agreement was 98.9%.

All defined negative samples were found negative in both assays and the evaluation of the results obtained for 39 blood donor samples gave mean values of 0.4 IUC Cvaluation of assays.

¹ Czamocka, B., Ruf, J., Ferrand, M., et al. (1985) Purification of the human thyroid persxidase and its identification as the microsomal antigen involved in autoimmune thyroid diseases. FEBS Lett. 190, 147-152

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# DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird symbol with three curved lines representing its wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the bird symbol. The logo is black and white.

Public Health Service

Ms. Karen E. Matis Manager, Regulatory Affairs and Quality Management Diagnostics Division, US Operations Pharmacia & Upjohn 7000 Portage Road 7425-248-01 Kalamazoo, Michigan 49001-0199

Re: K993585 Trade Name: Varelisa® TPO Antibodies Regulatory Class: II Product Code: JZO Dated: October 20, 1999 Received: October 22, 1999

Dear Ms. Matis:

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 comnerve 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 generals 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 Food 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 assumptions & ailure 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 .

JAN - 5 2000

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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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 Autman

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