(73 days)
- For the quantitative detection of IqG antibodies to thyroglobulin in human serum by enzyme immunoassay.
- The SeraQuest Anti-thyroglobulin test can be used with other serological tests and clinical findings, to aid in the diagnosis of thyroid diseases such as Autoimmune Thyroiditis and Graves' disease.
- For in vitro diagnostic use only.
The SeraQuest Anti-Thyroglobulin test is a solid-phase enzyme immunoassay (EIA), which is performed in microwells, at room temperature, in three thirty minute incubations. It has been developed to detect IqG antibodies which are directed against thyroglobulin, in human serum.
The Calibrators in the SeraQuest Anti-Thyroglobulin test kit have been assigned values based on the NIBSC standard. Test results are reported as international units per milliliter (IU/mL).
This document describes the validation study for the SeraQuest Anti-Thyroglobulin test.
1. Table of Acceptance Criteria and Reported Device Performance:
| Acceptance Criteria (Implicit from Predicate Equivalence) | Reported Device Performance (SeraQuest vs. Varelisa) |
|---|---|
| Relative Sensitivity: Expected to be comparable to the predicate device, demonstrating adequate detection of positive cases. | Relative Sensitivity: 97.0% (95% C.I.: 91.4% - 100%) |
| Relative Specificity: Expected to be comparable to the predicate device, demonstrating adequate exclusion of negative cases. | Relative Specificity: 100% (95% C.I.: 99.9% - 100%) |
| Overall Agreement: Expected to be high, indicating substantial concordance between the device and the predicate. | Overall Agreement: 99.2% (95% C.I.: 97.5% - 100%) |
2. Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Size: 144 serum specimens.
- Data Provenance: The study was conducted at Quest International, Inc., and the specimens were "serum specimens," implying human origin. The document does not explicitly state the country of origin or whether the data was retrospective or prospective. Given the nature of a 510(k) submission for device clearance, it is generally assumed to be a prospective or at least properly collected retrospective dataset for regulatory purposes.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This study did not use human experts to establish ground truth. Instead, it used a predicate device (Pharmacia Varelisa TG Antibodies test) as the reference standard. The performance of the SeraQuest Anti-Thyroglobulin test was compared directly to this established and legally marketed device.
4. Adjudication Method for the Test Set:
- No adjudication method by human experts was used for the test set. The comparison was directly against the results of the predicate device. When a discordant result occurred between the SeraQuest and Varelisa tests (1 specimen), it was further tested by a second legally marketed device, the Scimedix Anti-Thyroglobulin Test. This serves as a form of secondary verification rather than adjudication by expert consensus.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is an in-vitro diagnostic device comparison, not an imaging or clinical diagnostic aid that typically involves human readers.
6. Standalone (Algorithm Only) Performance Study:
- Yes, a standalone performance study was done. The SeraQuest Anti-Thyroglobulin test (the algorithm/device) was run independently on the 144 serum specimens, and its results were then compared to the results obtained from the predicate device (Pharmacia Varelisa TG Antibodies test), which also operated in a "standalone" fashion.
7. Type of Ground Truth Used:
- The "ground truth" used in this study was the results obtained from a legally marketed predicate device (Pharmacia Varelisa TG Antibodies test). This is a common approach for demonstrating substantial equivalence for in-vitro diagnostic devices. For the one discordant specimen, a second legally marketed device (Scimedix Anti-Thyroglobulin Test) was used for further verification, which gave an equivocal result.
8. Sample Size for the Training Set:
- The document does not explicitly state the sample size used for a "training set." This type of in-vitro diagnostic device likely undergoes development and internal validation and optimization with various samples, but the FDA submission focuses on the validation against a predicate device using a specific test set. The 144 specimens were for the performance study, not explicitly described as a training set.
9. How the Ground Truth for the Training Set Was Established:
- As a training set is not explicitly described or quantified, the method for establishing its ground truth is not provided. However, for the development and optimization of such an assay, ground truth would typically be established through a combination of well-characterized clinical samples (e.g., from patients with confirmed autoimmune thyroiditis or Graves' disease, and healthy controls), using reference methods or established clinical diagnoses.
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APPENDIX 3.
| 510(k) SUMMARY | K023592 | |
|---|---|---|
| Applicant: | Quest International, Inc.1938 N.E. 148th TerraceNorth Miami, FL 33181 | FEB 06 2003 |
| Registration No. | 1061839 | |
| Contact Person: | Robert A. Cort, V.P., Quality Assurance | |
| Telephone: | (305) 948-8788 | |
| Telefax: | (305) 948-4876 | |
| Manufacturing Site: | Same as above | |
| Device: | SeraQuest® Anti-Thyroglobulin | |
| Device Name: | Anti-Thyroglobulin, Multiple autoantibodies immunological test system(21CFR § 866.5660) | |
| Device Classification: | Class II (Performance Standards) |
Description:
The SeraQuest Anti-Thyroglobulin test is a solid-phase enzyme immunoassay (EIA), which is performed in microwells, at room temperature, in three thirty minute incubations. It has been developed to detect IqG antibodies which are directed against thyroglobulin, in human serum.
The Calibrators in the SeraQuest Anti-Thyroglobulin 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 thyroglobulin antibodies directed against thvroolobulin antiqen (if present) are immobilized in the wells. Residual sample is eliminated by washing and draining, and coniugate (enzyme-labeled antibodies to human IgG) is added and incubated. If laG antibodies to thyroglobulin antigen are present, the conjugate will be immobilized in the wells. Residual conjugate is eliminated by washing and the enzyme substrate is added and incubated. In the presence of the enzyme, the substrate is converted to a vellow endproduct which is read photometrically at 405 nm.
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itended Use:
Intended Use: The Anti-Thyroglobulin test is intended for the quantative detection of human IgG antibodies to thyroglobulin antigen, in human serum by enzyme immunoassay. The presence of antithyroglobulin antibodies can be used with other serological tests and clinical findings to aid in diagnosing individuals with Autoimmune Thyroditis and Grave's Disease. For In Vitro Diagnostic Use Only.
Predicate Device:
The SeraQuest Anti-Thyroglobulin test is substantially equivalent in intended use and performance, to the Pharmcia Varelisa TG Antibodies, Freiburg, Germany.
Summary of Technological Characteristics:
| Characteristic | SeraQuestAnti-ThyroglobulinTest | PharmaciaVarelisaTG Antibodies Test |
|---|---|---|
| Description: | Enzyme Immunoassay | Enzyme Immunoassay |
| Intended Use: | The detection of IgGantibodies againstthyroglobulinin human serum. | The detection of IgGantibodies againstthyroglobulinin human serum. |
| Solid Phase: | Polystyrene Microwell | Polystyrene Microwell |
| Antigen : | Purifiedthyroglobulin(human) | Purifiedthyroglobulin(human) |
| Number of Incubation Periods: | Three | Three |
| Sample Dilution: | 1:51 | 1:101 |
| Sample IncubationDuration: | 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 |
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Quest International, Inc., 1938 N.E. 148th Terrace, N. Miami, FL 33181 Page No. 75
| Conjugate Volume: | 100 μl | 100 μl |
|---|---|---|
| Conjugate Incubation Duration: | 30 minutes | 30 minutes |
| Substrate: | p-Nitrophenylphosphate | TMB |
| Subtrate Volume: | 100 μl | 100 μl |
| Substrate Incubation Duration: | 30 minutes | 10 minutes |
| Stop Reagent: | 0.5 M Trisodiumphosphate | 0.34 MSulfuric acid |
| Stop Reagent Volume: | 100 μl | 50 μl |
| Readout: | Spectrophotometric | Spectrophotometric |
| Wavelength: 405 nmReference Wavelength: | 450 nm620 nm | 450 nm |
| Normalization: | Standard Curve | Standard Curve |
| Reporting Unit: | IU / mL | IU / mL |
Summary of Clinical Testing:
APPENDIX 3.
Experimental Procedure
To challenge the cutoff values. 144 serum specimens were tested at Quest International. Inc., concurrently by the SeraQuest Anti-Thyroglobulin test, and the Varelisa TG Antibodies test (Pharmacia & Upichn Diagnostics). 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 144 specimens tested, 33 were positive, 84 were equivocal in both the SeraQuest and Varelisa tests (please see Table C-3). Of the 21 specimens remaining, 1 specimen which was negative by the Varelisa test, was positive by the SeraQuest test; 14 specimens which ··ere negative in the SeraQuest test, were equivocal by the Varelisa test; and of the 6 which were Juivocal in the SeraQuest test, 4 were positive and 2 negative in the Varelisa test.
■
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Excluding the equivocal results, the sensitivity of the SeraQuest Anti-Thyroglobulin test relative to the Varelisa test was 97%, or 91.4% to 100% (95% C.I.); the specificity was 100%, or 99.9% to 100% (95% C.I.); respectively. The overall agreement was 99.2%, or 97.5% to 100% (95% C.I.).
TABLE 1.
RESULTS OF SeraQuest ANTI-THYROGLOBULIN ASSAYS AND PHARMACIA ANTI-THYROGLOBULIN ASSAYS ON 144 SERUM SPECIMENS.
| SeraQuest | ||||||
|---|---|---|---|---|---|---|
| PHARMACIA | POS | EQU | NEG | % | 95% C.I. | |
| POS | 33 | 4 | 1 | Relative Sensitivity | 97.0 | 91.4-100 |
| EQU | 0 | 6 | 14 | |||
| NEG | 0 | 2 | 84 | Relative SpecificityOverall Agreement | 10099.2 | 99.9-10097.5-100 |
- Excluding equivocal results.
** 95%Confidence Interval calculated by the normal method.
The specimen which gave discordant result was tested by a second legally marketed device, the Scimedix Anti-Thyroglobulin Test, Scimedix Corp., Denville, New Jersey. The sample gave an equivocal result with the Scimedix test.
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Image /page/4/Picture/1 description: The image shows a logo for the U.S. Department of Health and Human Services. The logo features a stylized abstract design of an eagle or bird-like figure with three curved lines representing its wings or feathers. The text "HUMAN SERVICES - USA" is arranged in a circular fashion around the top of the logo, and the word "DEPARTMENT" is positioned along the left side.
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: K023592
Trade/Device Name: SeraQuest Anti Thyroglobulin Regulation Number: 21 CFR 866.5870 Regulation Name: Thyroid Autoantibody Immunological Test System Regulatory Class: Class II Product Code: DDC 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, 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).
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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 (301) 594-3084. 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 (800) 638-2041 or (301) 443-6597 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): K 023592
Device Name: SeraQuest Anti-Thyroglobulin
Indications For Use:
-
- For the quantitative detection of IqG antibodies to thyroglobulin in human serum by enzyme immunoassay.
-
- The SeraQuest Anti-thyroglobulin test can be used with other serological tests and clinical findings, to aid in the diagnosis of thyroid diseases such as Autoimmune Thyroiditis and Graves' disease.
- ર્જ 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)
Pleeves for S. Bautista
(Division Sign-Off)'
Division of Clinical Laboratory Devices
510(k) Number K023592
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use__
(Optional Format 1-2-96)
§ 866.5870 Thyroid autoantibody immunological test system.
(a)
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.(b)
Classification. Class II (performance standards).