The Access Thyroglobulin Antibody II (TgAb) assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of thyroglobulin antibody levels in human serum and plasma using the Access Immunoassay Systems. The measurement of thyroid autoantibodies may aid in the diagnosis of Hashimoto's disease, nontoxic goiter, and Graves' disease.

Device Description

The Access Thryoglobulin Antibody II reagents, calibrators, and the Access Immunoassay Analyzers (Access, Access 2, Synchron LXi 725, UniCel DxC 600i, and UniCel DxI 800) comprise the Access Immunoassay Systems for the determination of thyroglobulin antibody (TgAb) levels in human serum and plasma.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Access Thyroglobulin Antibody II Assay, based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Imprecision
Within-run CV	4.0% CV to 5.8% CV
Between-run CV	2.7% CV to 5.1% CV
Total Imprecision	4.8% CV to 7.0% CV
Low Dose Imprecision (SD)	0.3 to 0.8 SD
Dilution Recovery (Linearity)	Mean % recovery ranged from 118% to 127%
Analytical Sensitivity (Lowest detectable level distinguishable from zero with 95% confidence)	0.9 IU/mL
Methods Comparison
Positive % Agreement with predicate device	95%
Negative % Agreement with predicate device	99.6%
Overall Percent Agreement with predicate device	99%
Analytical Specificity (No significant interference from potential sample contaminants)	No significant interference from bilirubin, hemoglobin, human serum albumin, triglycerides, and autoantibodies.
Expected Values (95% non-parametric upper reference limit in normal population)	Below 4 IU/mL (137 screened samples) and 96% of 519 normal samples below 4 IU/mL

Study Details:

Sample size used for the test set and the data provenance:
- Methods Comparison: 832 values were used for comparison. The document does not explicitly state the country of origin, but given the applicant is in the US and the clinical studies for expected values were in the US, it is highly likely this data is from the United States. The study appears to be retrospective as it compares the new device with a "commercially available enzyme immunoassay kit" which implies existing samples.
- Imprecision, Dilution Recovery, Analytical Sensitivity, Analytical Specificity: Sample sizes are not explicitly given for each of these analytical studies, but details like "multiple dilutions," "20 replicates of the zero calibrator," and "sera samples obtained in the United States" are mentioned. For Expected Values, 137 screened samples and an additional 519 normal samples were collected in the United States. These appear to be prospective collections based on specific screening criteria.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is an immunoassay for quantitative determination of antibody levels. The "ground truth" for the analytical studies (imprecision, linearity, sensitivity, specificity) is based on the inherent properties of the assay and reference materials, not expert interpretation.
- For the Methods Comparison, the "ground truth" was established by a "commercially available enzyme immunoassay kit." This implicitly means the established performance of that predicate device determined the reference. No human experts are mentioned for establishing ground truth in this context.
- For Expected Values, the "ground truth" for "normal" was defined by specific clinical criteria (serum TSH levels, no personal/family history of thyroid disease, absence of non-thyroid autoimmune disease). This relies on clinical diagnosis and laboratory results rather than expert consensus on individual cases for the test set.
Adjudication method for the test set:
- Not applicable as this is an immunoassay device, and the "ground truth" in the analytical studies is based on established laboratory methods, reference ranges, or a comparator device's results, not on expert adjudication of individual case results.
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:
- Not applicable. This device is an in vitro diagnostic (IVD) immunoassay for quantitative measurement, not an AI-assisted diagnostic imaging or interpretation device that would involve human readers.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance characteristics (imprecision, dilution recovery, analytical sensitivity, analytical specificity, methods comparison) reflect the standalone performance of the Access Thyroglobulin Antibody II Assay as an automated immunoassay system. There is no human-in-the-loop component described for its primary function of quantitative determination.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For analytical studies:
  - Imprecision, Dilution Recovery, Analytical Sensitivity, Analytical Specificity: Ground truth is based on the intrinsic properties of the assay system, known standards, and controlled experimental conditions typical for IVD assay validation.
  - Methods Comparison: Ground truth was established by the results from a commercially available enzyme immunoassay kit (the predicate device).
- For clinical studies (Expected Values): Ground truth for "normal" was established by clinical criteria (TSH levels, medical history) rather than a single type of definitive outcome or pathology for each individual.
The sample size for the training set:
- The document describes the validation of the device, not the development of an algorithm that requires a "training set." This is an immunoassay, not a machine learning model. Therefore, the concept of a training set in the AI/ML sense is not applicable. The studies described are for validation of the assay's performance.
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" in the context of this immunoassay.

Summary

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510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K062516

Applicant:	Beckman Coulter, Inc.Immunodiagnostics Development Center1000 lake Hazeltine DriveChaska, MN 55318	OCT - 5 2006
Contact Person:	Tyler FoutchRegulatory Affairs SpecialistPhone: 952.368.1653Fax: 952.368.7610
Date Prepared:	September 26, 2006
Proprietary Name:	Thyroglobulin Antibody II and Thyroglobulin Antibody II Calibratorson the Access® Immunoassay Systems
Common Name:	Immunoassay for the determination of thyroglobulin antibodies
Classification Name:	System, Test, Thyroid Autoantibody
Product Classification:	Class II
Product Code:	Reagent- DDCCalibrator Secondary- JIT
Predicate Device:	Access® Thyroglobulin Antibody Assay - K012208
Device Description:	The Access Thryoglobulin Antibody II reagents, calibrators, and theAccess Immunoassay Analyzers (Access, Access 2, Synchron LXi725, UniCel DxC 600i, and UniCel DxI 800) comprise the AccessImmunoassay Systems for the determination of thyroglobulinantibody (TgAb) levels in human serum and plasma.
Intended Use:	The Access Thyroglobulin Antibody II (TgAb) assay is aparamagnetic particle, chemiluminescent immunoassay for thequantitative determination of thyroglobulin antibody levels in humanserum and plasma using the Access Immunoassay Systems. Themeasurement of thyroid autoantibodies may aid in the diagnosis ofHashimoto's disease, nontoxic goiter, and Graves' disease.

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Comparison of Technological Characteristics

Attribute	Access Thyroglobulin Antibody	Access Thyroglobulin Antibody II
IntendedUse	For the quantitative determination ofThyroglobulin antibody levels in humanserum and plasma.	For the quantitative determination ofThyroglobulin antibody levels in humanserum and plasma.
AssayPrinciples	The Access Thyroglobulin Antibodyassay is a sequential two-stepimmunoenzymatic ("sandwich") assay.	The Access Thyroglobulin Antibodyassay is a sequential two-stepimmunoenzymatic ("sandwich") assay.
SolidSupport	Paramagnetic particles coated withstreptavidin and coupled to biotinylatedhuman thyroglobulin.	Paramagnetic particles coated withstreptavidin and coupled to biotinylatedhuman thyroglobulin.
DetectionSystem	Utilizes dioxetane-basedchemiluminescent substrate;Measures light production from achemiluminescent reaction.	Utilizes dioxetane-basedchemiluminescent substrate;Measures light production from achemiluminescent reaction.
Calibrator	Six levels (0, ~50, ~250, ~500, ~1000,and ~2500 IU/mL) Humanthyroglobulin antibody in human serumin a buffered protein solution withpreservatives.	Six levels (0, ~50, ~250, ~500, ~1000,and ~2500 IU/mL) Humanthyroglobulin antibody in human serumin a buffered protein solution withpreservatives.

Summary of Analytical Studies

Imprecision: Imprecision was tested for concentrations from approximately 27,0 to 721,0 IU/mL. The within run imprecision ranged from 4.0% CV to 5.8% CV. Between-run assay imprecision ranged from 2.7% CV to 5.1% CV. Total imprecision ranged from 4.8% CV to 7.0% CV. For low dose imprecision was tested for concentrations from approximately 1.7 to 10.5 IU/mL. The SD for these samples ranged from 0.3 to 0.8 SD.

Dilution Recovery (Linearity): Multiple dilutions of serum samples were analyzed. Mean % recovery ranged from 118% to 127%. Due to varying antigen specificity, affinity, and avidity of thyroglobuulin antibodies in their epitope reactions, some samples may not dilute linearly.

Methods Comparison: A comparison of 832 values using the Access Thyroglobulin Antibody II assay on the Access Immunoassay system and a commercially available enzyme immunoassay kit gave the following results using relative sensitivity, specificity and percent agreement:

	Commercially Available TgAb Assay
	+	-	Total
AccessTgAb IIAssay	136	3	139	Positive % Agreement =95%
	7	686	693	Negative % Agreement =99.6%
	Total	143	689	832	Percent Agreement =99%

Analytical Sensitivity: The lowest detectable level of TgAb distinguishable from zero (Access Thyroglobulin Antibody Calibrator S0) with 95% confidence is 0.9 IU/mL. This value is determined by processing a complete six point calibration curve, controls and 20 replicates of the zero calibrator in multiple assays. The analytical sensitivity value is calculated from the curve at the point that is two standard deviations from the mean measured zero calibrator signal.

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Analytical Specificity: There was no significant interference from potential sample contaminants (bilirubin, hemoglobin, human serum albumin, triglycerides, and autoantibodies).

Summary of Clinical Studies

Expected Values: Sera samples were obtained in the United States from males < 30 years of age following the criteria outlined by the National Academy of Clinical Biochemists (NACB) for establishing a normal reference range for thyroid antibody tests. The screening criteria included serum TSH levels between 0.5 and 2.0 mIU/L, no personal or family history of thyroid disease and absence of non-thyroid autoimmune disease. 137 screened samples were tested generating a 95% non-parametric upper reference limit below 4 IU/mL.

Additionally, 519 normal samples were collected in the United States from both males and females ranging in age from 18-74 years old. The screening criteria included serum TSH levels between 0.5 and 2.0 mIU/L no personal or family history of thyroid disease, and absence of nonthyroid autoimmune disease. 519 samples were tested. 96% of these samples fell below 4 IU/mL.

Conclusion: The Access® Thyroglobulin Antibody II and Thyroglobulin Antibody II Calibrators on the Access® Immunoassay Systems is substantially equivalent to the Access Thyroglobulin Antibody for the quantitative determination of thyroglobulin antibody in human serum and plasma.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it. The words "HUMAN SERVICES • USA" are written in a circular fashion above the symbol. The word "DEPARTMENT" is written below the symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Beckman Coulter, Inc. c/o Mr. Tyler Foutch Regulatory Affairs Specialist Immunodiagnostics Development Center 1000 Lake Hazeltine Dr. Chaska, MN 55318-1084

0C1 - 5 2006

Re: K062516

Trade/Device Name: Access Thyroglobulin Antibody II Assay and Access TPO Antibody Calibrators Regulation Number: 21 CFR 866.5870 Regulation Name: Thyroid Autoantibody Immunological Test System Regulatory Class: Class II Product Code: JNL, JIT Dated: August 25, 2006 Received: August 28, 2006

Dear Mr. Foutch:

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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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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 advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at (240) 276-0484. 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Robert Bookerf

Robert L. Becker, Jr., M.D., Ph.D Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety

Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K062516

Device Name: Access Thyroglobulin Antibody II Assay

Indications for Use:

The Access Thyroglobulin Antibody II Assay provides in vitro quantitative determination of thyroglobulin antibody levels in human serum and plasma using the Access Immunoassay Systems. The measurement of thyroid autoantibodies may aid in the diagnosis of Hashimoto's disease, nontoxic goiter, and Graves' disease.

Prescription Use _____________________________________________________________________________________________________________________________________________________________

Over-The-Counter Use
(21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Mana Chan

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K062516

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).