(75 days)
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.
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 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.
The provided text describes a 510(k) submission for a device modification of the Varelisa® TPO Antibodies EIA kit. The submission aims to establish substantial equivalence to a predicate device, the elias™ TM Antibodies assay.
Here's an analysis based on the provided text, addressing your specific questions:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in numerical terms (e.g., a specific percentage of agreement or a benchmark for R-value). Instead, the substantial equivalence is demonstrated through a correlation study comparing the modified device (Varelisa® TPO Antibodies) with the predicate device (elias™ TM Antibodies).
| Acceptance Criteria Category | Specific Metric (Inferred) | Reported Device Performance |
|---|---|---|
| Overall Agreement | High degree of similarity to predicate device | "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." |
| Negative Samples | All defined negative samples should be found negative | "All defined negative samples were found negative in both assays." |
| Blood Donor Samples | Mean values for blood donor samples (expected to be low/negative) | "the evaluation of the results obtained for 39 blood donor samples gave mean values of 0.4 IUC" (Inferred to be a low value indicating negativity) |
| Equivocal Range Handling | Agreement when accounting for differing equivocal ranges | "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%." |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 183 positive and negative samples were used for the correlation study, plus an additional 39 blood donor samples. So, the total number of samples used in these performance evaluations is 222 (183 + 39).
- Data Provenance: The text does not specify the country of origin of the data. It is implied to be retrospective, as it involves pre-existing samples (
183 positive and negative samplesand39 blood donor samples) being compared against a predicate device.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the text. This is a diagnostic assay, not an imaging AI device that would typically rely on human expert interpretation for ground truth. The "ground truth" for the test set is established by the results of the predicate device (elias™ TM Antibodies assay).
4. Adjudication Method for the Test Set
This information is not applicable for this type of in-vitro diagnostic device comparison. Adjudication methods like 2+1 or 3+1 are typically used in studies involving human interpretation (e.g., radiologists) where there might be disagreement in reading cases. Here, the comparison is directly between two assays, and discrepancies would be analyzed statistically, not through an adjudication process among human readers.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for evaluating AI's impact on human readers, typically in image interpretation scenarios. This submission concerns an in-vitro diagnostic assay and does not involve human readers interpreting AI outputs.
6. If a Standalone (i.e. algorithm only, without human-in-the-loop performance) was done
Yes, a standalone performance evaluation was done. The study directly compares the results of the Varelisa® TPO Antibodies assay (the modified device, which functions as a standalone algorithm/assay) with the results of the elias™ TM Antibodies assay (the predicate device, also a standalone assay). The performance metrics (R-value, agreement) reflect the assay's performance without human intervention in the result generation.
7. The Type of Ground Truth Used
The "ground truth" for the performance evaluation is the results obtained from the legally marketed predicate device, the elias™ TM Antibodies assay. The underlying assumption is that the predicate device provides an accepted standard for measuring TPO antibodies, and therefore, strong correlation with it demonstrates acceptable performance of the new device. The text also mentions the standardization against the "Anti-Thyroid Microsome Serum, NIBSC Research Standard 66/387," which serves as a common reference for both assays.
8. The Sample Size for the Training Set
The provided text does not contain information about a training set. This document describes a modification to an existing device (Varelisa TPO Antibodies) and its comparison to a predicate device for regulatory approval. While such assays likely undergo development and calibration, the specific details of a "training set" in the context of an AI/machine learning model are not relevant here, as this is a chemical/biochemical assay rather than an AI or ML-driven diagnostic.
9. How the Ground Truth for the Training Set was Established
As noted in point 8, information about a "training set" and its ground truth is not provided and is likely not applicable in the context of this device's type.
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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 & UpjohnDiagnostics Division, US Operation7425-248-17000 Portage RoadKalamazoo, MI 49001 |
| Manufacturer: | Pharmacia & Upjohn Diagnostics GmbH Co. KGMunzingerstrasse 7D-79111 Freiburg, Germany |
| Company Contact Person: | Karen E. MatisManager, Regulatory Affairs and QualityManagementDiagnostics Division, US Operation7000 Portage Road7425-248-01Kalamazoo, MI 49001(614) 794-3324 (Phone)(614) 794-0266 (Fax) |
| Device Name: | Varelisa® TPO Antibodies |
| Common Name: | Thyroid autoantibody immunological testsystem. |
| 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 (770) 488-7655.
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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. 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 (800) 638-2041 or (301) 443-6597, 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
§ 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).