ANTI-THYROGLOBULIN (TG) MICROPLATE ELISA by MONOBIND

The quantitative determination of thyroglobulin autoantibodies in human serum or plasma by a microplate enzymeimmunoassay. Measurements of Tg autoantibodies may aid in the diagnosis of certain thyroid diseases such as Hashimoto, Graves, and nontoxic goiter.

Device Description

The Monobind method is based on ELISA technology utilizing the streptavidin-blotin reaction to effect separation. Upon mixing blotinylated thyroglobulin antigen, and a serum containing the autoantibody (anti-Tg), reaction results between the biotinylated thyroglobulin antigen and the antibodies to form an immune complex. Simultaneously, the complex is deposited to the well through the high affinity reaction of streptavidin, coated on the well, and biotinylated thyroglobulin antigen. After incubation is complete, decantation or aspiration separates the unbound components. The enzyme linked species specific antibody (anti-h-igG) is then added to the microwells. The anti-h-lgG enzyme conjugate that binds to the immobilized immune complex in a second incubation are separated from unreacted material by a wash step. The enzyme activity in this fraction Is directly proportional to the antibody concentration in the specimen. By utilizing several different serum references of known antibody activity, a reference curve can be generated from which the antibody activity of an unknown can be ascertained.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Monobind Anti-Thyroglobulin (Tg) Microplate ELISA, based on the provided text:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Implicit)	Reported Device Performance
Clinical Comparison (method agreement with predicate device)	Linear regression: 0.995 correlation coefficient
	Equation: y = 9.79 + 0.969(x)
	Mean values: Reference method: 419.2 IU/ml; This method: 415.6 IU/ml
Linearity of Dilutions (Recovery)	Average 98.7% recovery

Study Details

Sample size used for the test set and the data provenance:
- Sample Size: 82 biological specimens.
- Data Provenance: The specimens were from "normal and disease states populations," including "Hashimoto's thyroiditis, Graves Disease, thyroid nodules as well as thyroid carcinoma." The text does not specify the country of origin, but it implies human serum or plasma samples. The study appears to be retrospective as it used existing biological specimens for comparison.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not explicitly state the number of experts or their qualifications. The "ground truth" for the test set appears to be established by the "reference method" (the Biomerica anti-thyroglobulin ELISA test), which is itself a validated diagnostic method. The values for comparison were "known antibody activity," implying established measurements from the predicate device.
Adjudication method for the test set:
- The document does not describe an adjudication method involving experts. The comparison was quantitative, based on linear regression between the new device's measurements and the predicate device's measurements.
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, an MRMC comparative effectiveness study was not done. This device is an ELISA kit, which is an in-vitro diagnostic test, not an AI-assisted imaging or diagnostic tool that would involve human readers in the classical sense.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, this study represents a standalone performance evaluation of the ELISA kit. The "algorithm" here is the chemical reaction and measurement process of the ELISA kit itself, without direct human interpretation influencing the numerical result.
The type of ground truth used:
- The primary ground truth used for performance comparison was the quantitative results obtained from a predicate device (Biomerica anti-thyroglobulin ELISA test), which is itself a legally marketed diagnostic method. This is a form of clinical comparison against an established method. The results were also tied to "known antibody activity" and specimens from "disease states," implying a correlation with clinical diagnoses.
The sample size for the training set:
- The document does not specify a separate "training set" in the context of device development. For an ELISA kit, method development (e.g., optimizing reagent concentrations) would involve internal testing, but the 82 specimens discussed are for the validation/test set used to demonstrate substantial equivalence.
How the ground truth for the training set was established:
- As there's no explicitly mentioned "training set" with ground truth establishment described for this type of device, this question is not directly applicable in the context of the provided information. Instead, the "ground truth" for calibrators (standards) used in the assay itself is established by preparing them from "diluted human serum" "standardized against the same international reference material 1st IRP 65/93." This ensures the traceability and accuracy of the calibration curve.

Summary

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Image /page/0/Picture/0 description: The image shows the logo for MONOBIND, INC. The logo consists of a stylized letter "B" formed by two interconnected shapes. Below the logo, the text "MONOBIND, INC." is printed in a bold, sans-serif font. Underneath the company name, the date "May. 14, 97" is printed in a bold, italicized font.

K 921835

JUL - 3 1997

510(k) Summarv

Dear Sir:

Monobind Inc., registration number 2020726, plans to introduce into commercial distribution an ELISA kit for the determination of thyroglobulin autoantibodies in human serum or plasma.

The proprietary name is Anti-Thyroglobulin (Tg) Microplate ELISA and the usual name is Anti-Ta ELISA. This device classification name is - thyroid autoantibody immunological test system - product code DDC (per 21 CRF section 866.5870).

This device is substantially equivalent to the Biomerica anti-thyroglobulin ELISA test, which predicates the new device.

The contact Individual for this submission is Dr. Frederick R. Jerome.

The intended use of the device: The quantitative determination of thyroglobulin (Tg) autoantibodies in human serum or plasma by a microplate enzymeimmunoassay.

The technological characteristics of the new device compared to the predicate device are very similar. This includes ELISA technology with highly purified thyroglobulin antigen. and diluted human serum prepared calibrators (standardized against the same international reference material 1st IRP 65/93). A difference lles in the use of anti-hlgG -HRP (Monobind method) versus HRP-Protein A (Biomerica method) to expose the antibody activity on the solid phase. However, both reagents' function is to detect anti-h-IgG on the solid phase. The enzyme and substrate systems are the same.

Substantial equivalency was based on clinical comparison (linear regression), using 82 biological specimens from normal and disease states populations. The disease states Included; Hashimoto's thyroiditis, Graves Disease, thyroid nodules as well as thyroid carcinoma. The mean values for reference method and this method are 419.2 IU/ml and 415.6 IU/ml respectively. The equation to a straight-line [ v= 9.79+0.969 (x) ] and correlation coefficient (0.995) Indicates good method agreement.

In addition, linearity studies showed an average 98.7% recovery when specimens were diluted and compared to the dose response curve.

729 West 16" Street , Costa Mesa , CA (USA) 92627 Phone: (714) 642-4830 FAX: (714) 650-8459

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Dr. Frederick Jerome 729 West 16th Street, C-4 Costa Mesa, CA 92627

JUL - 3 1997

Re: K971835 Trade Name: Anti-thyroglobulin (Tg) Microplate ELISA Regulatory Class: II Product Code: DDC Dated: May 14, 1997 Received: May 19, 1997

Dear Dr. Jerome:

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 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 Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP 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 promarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Preduct Radiation Control provisions, or other Federal Laws or Regulations.

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.

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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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Toutman

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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Indications for Use Statement

510(k) Number (if known): K971835

Device Name: Anti-thyroglobulin(Tg) Microplate ELISA

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Deborah Moore for
Dr. Peter Maxim

(Division Sign-00
Division of Clinical Laboratory Devices
510(k) Number K971835

Prescription Use

Over-The-Counter Use

(Per 21 CFR 801.109)

(Optional Folmat 1-2-96)

Regulation Number and Section

§ 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).