The Nichols Advantage® Chemiluminescence Thyroglobulin Autoantibodies Immunoassay is designed for use with the Nichols Advantage® Specialty System for the quantitative determination of thyroglobulin autoantibodies (TgAb) in human serum. This assay is intended to aid in the diagnosis and assessment of patients with autoimmune thyroid disease.

Device Description

TgAb chemiluminescence immunoassay is a two-site The Nichols Advantage® immunometric method based on binding anti-thyroglobulin antibodies in human serum to human thyroglobulin (Tg). Total duration of assay is 31.5 minutes at 37°C.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study details for the Nichols Advantage® Chemiluminescence Thyroglobulin Autoantibodies Immunoassay:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" for each performance characteristic in a separate, defined section. However, by comparing the new device's performance to the predicate device, especially in areas like precision and recovery, we can infer the predicate's performance acts as an implicit benchmark for acceptability, striving for comparable or improved results.

Feature	Inferred (or Explicit) Acceptance Criteria (based on predicate or desired performance)	Reported Device Performance (Nichols Advantage TgAb)
Precision
Intra-Assay - Low Mean TgAb	Similar to predicate (e.g., %CV < 8.7%)	Mean: 3.6 UI/mL, %CV: 7.2
Intra-Assay - Medium Mean TgAb	Similar to predicate (e.g., %CV < 5.9%)	Mean: 13.8 UI/mL, %CV: 6.1
Intra-Assay - High Mean TgAb	Not explicitly compared to predicate for specific value, but likely a low %CV	Mean: 60.2 UI/mL, %CV: 5.8
Inter-Assay - Low Mean TgAb	Similar to predicate (e.g., %CV < 14.2%)	Mean: 4.0 UI/mL, %CV: 12.9
Inter-Assay - High Mean TgAb	Similar to predicate (e.g., %CV < 7.7%)	Mean: 13.7 UI/mL, %CV: 6.1
Inter-Assay - Very High Mean TgAb	Not explicitly compared to predicate for specific value, but likely a low %CV	Mean: 55.0 UI/mL, %CV: 6.8
Recovery	Comparable to predicate (83 - 111%)	94 - 113%
High Dose Hook	Demonstrate absence of hook effect up to a specified high concentration	4,000 IU/mL
Specificity and Crossreactivity	>90% recovery with potential cross-reactants	Recombinant hTPO @ 200 mg/L: 95% recovery; TPO Ab @ 2000 IU/mL: 91% recovery
Method Comparison (Agreement vs. Predicate)	High agreement, sensitivity, and specificity (likely >90%)
Relative Sensitivity	High (>90%)	100%
Relative Specificity	High (>90%)	98.3%
Agreement	High (>90%)	98.6%
Reportable Range	Comparable or improved over predicate (approx. 0.2-60 IU/mL)	Approx. 0.3-90 IU/mL
Reference Range	Define a clinical reference range	Up to 1 IU/mL

2. Sample Size Used for the Test Set and Data Provenance:

The document provides some sample sizes for specific tests but not a single, overarching "test set" sample size for comparison studies.

Precision (Intra-Assay/Inter-Assay):
- For each mean level, N=20 was used for both intra-assay and inter-assay precision measurements for the Nichols Advantage TgAb.
- For the predicate device, N=20 (intra-assay) and N=15-22 (inter-assay) were used.
Method Comparison: The "Range of results" states "Undetectable to 2,089 IU/mL" for the Nichols Advantage and "Undetectable to 2,190 IU/mL" for the predicate. This suggests a range of patient samples were used, but the number of samples is not explicitly stated. The Binomial Test Statistic P(X) = 0.25 is mentioned, which implies statistical analysis was performed on a set of comparative data, but the exact N is missing.
Data Provenance: Not specified. It's unclear if the data is prospective or retrospective, or the country of origin of the samples.

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 document. For an immunoassay, "ground truth" is typically established by the result of a reference method or clinical diagnosis, not by experts reviewing images.

4. Adjudication Method for the Test Set:

This information is not provided. Given that this is an immunoassay, adjudication methods like those used for image interpretation (e.g., 2+1, 3+1) are not typically applicable. The "ground truth" would be the result from a reference standard or predicate device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size:

No, an MRMC study was not done. This type of study (evaluating multiple human readers with and without AI assistance on multiple cases) is relevant to diagnostic imaging devices with human interpretation components. The Nichols Advantage® device is an automated immunoassay, which does not involve human readers interpreting "cases" in that sense.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Yes, implicitly. The entire study described for the Nichols Advantage® device represents its standalone performance. As an automated immunoassay, it produces quantitative results without direct human interpretive intervention beyond running the assay according to instructions. The performance characteristics (precision, recovery, specificity, method comparison) are all measures of the algorithm/device itself. There is no "human-in-the-loop" component in the assay's operation or result generation.

7. The Type of Ground Truth Used:

For precision, the ground truth is the measured concentration of TgAb in spiked or control samples.
For recovery, it's the expected concentration after spiking.
For specificity/cross-reactivity, it's the known absence/presence of interferents.
For the method comparison, the "ground truth" is established by the results of the predicate device. The study aims to show substantial equivalence between the new device and the predicate.
The "Intended Use" states it is "to aid in the diagnosis and assessment of patients with autoimmune thyroid disease." This suggests that ultimately, the assay results are correlated with clinical diagnoses or patient outcomes related to autoimmune thyroid disease, though the study presented is focused on analytical performance and comparison to a predicate, not clinical outcome validation.

8. The Sample Size for the Training Set:

This information is not applicable or not provided. This device is a traditional immunoassay, not an AI/machine learning model that typically undergoes a "training" phase with a large dataset. Its performance is based on its chemical and optical detection mechanisms, which are inherently "trained" or designed through biochemical engineering, not data-driven machine learning.

9. How the Ground Truth for the Training Set Was Established:

This information is not applicable or not provided for the same reasons as point 8.

Summary

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JAN 26 1999

510(k) SUMMARY

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

510(k) Number: K983992

1. Name of Submitter, Contact Person and Date Summary Prepared:

Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, CA 92675 Phone: 714-240-52690 Fax: 714-240-5313

Contact Person: Jimmy Wong Date Prepared: January 21, 1999

2. Device Name

Trade/Proprietary Name:	Nichols Advantage® Chemiluminescence ThyroglobulinAutoantibodies Immunoassay
Common/Usual Name:	Anti-Tg Assay
Classification Name:	Thyroid, Autoantibody Immunological Test System

3. Predicate Device:

Nichols Institute Diagnostics substantial equivalence to the We claim Chemiluminescence Thyroglobulin Autoantibodies assay.

4. Device Description:

5. Intended Use

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6. Comparison to predicate device:

The Nichols Advantage® Thyroglobulin Autoantibodies Immunoassay is substantially equivalent to other products in commercial distribution for similar use. Most notably it is substantially equivalent to the Nichols Institute Diagnostics Chemiluminescence Thyroglobulin Autoantibodies assay.

The following tables compare the new device with the predicate device.

Similarities:

Intended Use: For the quantitative determination of TgAb in human sera. .
Both assays use highly purified thyroglobulin of human origin. .
Both assays use human serum for the test sample. .
The sensitivity of both assays is sufficient to measure TgAb levels found in patients . with autoimmune thyroid disease.
Pooled sera with high concentrations of TgAb are used as standards in the both ● assays. The standard is calibrated to WHO 1st IRP 65/93.
Both methods are based on acridinium conjugated Tg and biotin coupled Tg to . produce a sandwich complex with the patient's TgAb.

Differences:

Feature	Nichols Advantage TgAb	Predicate Device
Sample Size	20 uL1:15 dilution with assay diluent.60 uL of the diluted sample is assayed.	100 uL1:10 dilution with assay dilutent.100 uL of the diluted sample is assayed.
Calibration	Two-point calibration stable forone week from workingcalibration curve, or whencontrols are out of range.	Full calibration curve with everyrun.
Assay Set-up	Automated	Manual
Solid Phase	Streptavidin coated magneticparticles. Streptavidin-biotinseparation technology.	6 mm bead
Incubation	31.5 minutes at 37C	2 hours at room temperatureusing a rotator.
Reportable Range	Approx. 0.3-90 IU/mL	Approx. 0.2-60 IU/mL.

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Performance Characteristics:

എയാറ്റ് സംസ്ഥാപനം ചെയ്തു. അവലംബം

Feature	Nichols Advantage TgAb			Predicate Device
Precision	Mean(UI/mL)	N	%CV	Mean(UI/mL)	N	%CV
Intra-Assay	3.6	20	7.2	1.9	20	8.7
	13.8	20	6.1	41	20	5.9
	60.2	20	5.8
Inter-Assay	4.0	20	12.9	3.1	15	14.2
	13.7	20	6.1	36	22	7.7
	55.0	20	6.8
Recovery	94 - 113%			83 - 111%
High Dose Hook	4,000 IU/mL			Not Done
Specificity and Crossreactivity
Recombinant hTPO @ 200 mg/L	95% recovery			Not Done
TPO Ab @ 2000 IU/mL	91% recovery			Not Done
Method Comparison:
Range of results	Undetectable to 2,089 IU/mL			Undetectable to 2,190 IU/mL
Binomial Test Statistic	P(X) = 0.25
Relative Sensitivity	100%
Relative Specificity	98.3%
Agreement	98.6%
Reference Range	Up to 1 IU/mL			Up to 2 IU/mL

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Image /page/3/Picture/2 description: The image shows a black and white emblem of the U.S. Department of Health & Human Services. The emblem features a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged around the eagle. The text is oriented vertically along the left side of the emblem.

JAN 26 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Mr. Jimmy Wong Manager, Clinical and Technical Affairs Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, California 92675

Re: K983992

Trade Name: Nichols Advantage® Chemiluminescence Thyroglobulin Autoantibodies Immunoassay Regulatory Class: II Product Code: JZO Dated: November 6, 1998 Received: November 9, 1998

Dear Mr. Wong:

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 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 vour 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 Good 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. 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 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.

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Page 2

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 yours,

Steven Sutman

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): K983992

Device Name: Nichols Advantage® Chemiluminescence Thyroglobulin Autoantibodies Immunoassay

Indications For Use:

Chemiluminescence Thyroglobulin Autoantibodies Advantage® The Nichols Immunoassay is designed for use with the Nichols Advantage® Specialty System for the minitative determination of thyroglobulin autoantibodies (TgAb) in human serum. This assay is intended to aid in the diagnosis and assessment of patients with autoimmune thyroid disease.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices	K983992
510(k) Number

Prescription Use	OR	Over-The-Counter Use
(Per 21 CFR 801.109)		(Optional Format 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).