The Nichols Advantage™ Chemiluminescence Thyroid Peroxidase Autoantibodies Immunoassay is intended for use on the Nichols Advantage™ Specialty System for the quantitative determination of Thyroid Peroxidase Autoantibodies (TPOAb) in human serum as an aid in the diagnosis and assessment of patients with autoimmune thyroid disease.

Device Description

The Nichols Advantage™ Anti-TPO is a two-site chemiluminescence assay for use with the Nichols Advantage™ Specialty System

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study proving the device meets them, presented in the requested format:

Acceptance Criteria and Device Performance Study

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" for each performance characteristic. However, by comparing the performance of the new device (Nichols Advantage™ Chemiluminescence Anti-TPO) to the predicate device (Nichols Institute Diagnostics Chemiluminescence Anti-TPO), it can be inferred that the performance of the new device should at least be comparable to or better than the predicate, or meet established laboratory standards for clinical assays. For the purpose of this analysis, the predicate device's performance will be used as a reference point for implicit acceptance.

Feature	Acceptance Criteria (Implied from Predicate/General Lab Standards)	Reported Device Performance (Nichols Advantage™)
Intra-Assay Precision	%CV values comparable to or lower than predicate (e.g., <10.7%)	Low %CVs (3.9 - 5.4%)
Inter-Assay Precision	%CV values comparable to or lower than predicate (e.g., <9.7%)	Low %CVs (9.1 - 14.3%)
Recovery	Comparable to predicate (e.g., 92 - 113%)	94 - 107%
Parallelism	Acceptable linearity (predicate did not report)	88 - 117%
High Dose Hook Effect	No hook effect up to a certain concentration (predicate not reported)	> 4,000 IU/mL
Specificity/Cross-Reactivity	No interference from common autoantibodies/thyroglobulin	Undetectable (Anti-Thyroglobulin, Thyroglobulin)
Method Comparison	Preliminary Reference Range established	Normal < 2.0 IU/mL
Range of Results	Broad measurement range comparable to predicate	0.02 - 1548 IU/mL
Binomial Test Statistic	P-value indicating statistical agreement	P(X) = 0.0611
Relative Sensitivity	High sensitivity (e.g., comparable to predicate)	94.1%
Relative Specificity	High specificity (e.g., comparable to predicate)	94.2%
Agreement	High overall agreement	94.1%
Sensitivity (Limit of Detection)	Comparable to predicate (0.2 IU/mL)	0.5 IU/mL in serum

Note on Sensitivity: The "Sensitivity" listed under "Similarities" (0.5 IU/mL) for the Nichols Advantage™ is lower than the predicate (0.2 IU/mL), meaning the predicate assay can detect lower concentrations. However, both are stated to be "sufficient to measure Anti-TPO autoantibody levels found in patients with autoimmune disease." Therefore, 0.5 IU/mL for the Nichols Advantage™ is still implicitly accepted as meeting clinical needs.

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

The document provides sample sizes for different performance characteristics:

Intra-Assay & Inter-Assay:
- For Nichols Advantage™: 20 replicates for each of the three concentration levels tested (low, medium, high).
- For Predicate Device: 21, 22, or 23 replicates for each concentration level.
Other characteristics (Recovery, Parallelism, High Dose Hook Effect, Specificity, Method Comparison, Relative Sensitivity, Relative Specificity, Agreement): The specific sample sizes for these tests are not explicitly stated in the provided text.

Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

This information is not provided in the document. The study appears to be a laboratory performance evaluation of an in-vitro diagnostic device measuring TPO autoantibodies, not an imaging or diagnostic interpretation study requiring expert consensus for ground truth. The "ground truth" for such assays is typically established by reference methods or clinical diagnosis supported by various laboratory and clinical findings.

4. Adjudication Method for the Test Set

Since this is an in-vitro diagnostic device measuring analytes, and not a human-interpreted diagnostic output, an adjudication method (like 2+1 or 3+1) involving human experts is not applicable and therefore, not specified.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

An MRMC study is relevant for diagnostic devices that involve human interpretation of results (e.g., medical imaging). This is an in-vitro diagnostic assay for TPO autoantibodies. Therefore, an MRMC comparative effectiveness study was not performed or is not relevant in this context. The document does not mention any human reader assistance or effect size of AI.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

This device is an automated chemiluminescence immunoassay system. Its performance, as described in the "Performance Characteristics" section, represents the standalone (algorithm/system only without human-in-the-loop performance). The results presented (precision, recovery, specificity, sensitivity, etc.) reflect the intrinsic analytical performance of the device without human interpretation or intervention in the measurement process itself, beyond standard laboratory procedures for operating the instrument and handling samples.

7. Type of Ground Truth Used

For an immunoassay like this, the ground truth is typically established by:

Reference materials/known concentrations: For analytical performance characteristics like precision, recovery, and linearity.
Clinical Diagnosis/Known Patient Status: For determining relative sensitivity, specificity, and agreement, where TPOAb levels are correlated with a clinical diagnosis of autoimmune thyroid disease.
Correlation with a predicate device or established method: For method comparison studies.

The document mentions "Preliminary Reference Range: Normal < 2.0 IU/mL," implying a comparison against clinically defined normal and abnormal populations, but it does not explicitly detail how these clinical ground truths were established (e.g., biopsy, long-term follow-up, other clinical markers).

8. Sample Size for the Training Set

The document describes an assay. It does not mention any "training set" in the context of machine learning or AI models. The development and calibration of the assay would likely involve numerous samples, but these are not explicitly referred to as a "training set" in this context.

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

As there is no mention of a "training set" in the context of an AI/ML model, this information is not applicable and therefore, not provided. The ground truth for the assay's development and validation would have been established through a combination of well-characterized samples, reference standards, and clinical samples with known diagnoses, as is standard practice for IVDs.

Summary

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K982866 11.0 510(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.

not known 510(k) Number:

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

Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, CA 92675-4703 Phone: 949-240-5260 Fax: 949-240-5313

Contact Person: Jimmy Wong Date Prepared: July 31, 1998

2. Device Name

Trade/Proprietary Name:	Nichols Advantage™ Chemiluminescence ThyroidPeroxidase Autoantibodies Immunoassay
Common/Usual Name:	Anti-TPO Assay
Classification Name:	Thyroid, Autoantibody Immunological Test System

3. Predicate Device:

substantial equivalence the Nichols Institute Diagnostics We claim to Chemiluminescence Thyroid Peroxidase Autoantibodies Immunoassay (K931311, Cleared 5/14/93).

4. Device Description:

The Nichols Advantage™ Anti-TPO is a two-site chemiluminescence assay for use with the Nichols Advantage™ Specialty System

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5. Intended Use

6. Comparison to predicate device:

The Nichols Advantage™ Anti-TPO is substantially equivalent to other products in commercial distribution for similar use. Most notably, it is substantially equivalent to the NID Chemi Anti-TPO Immunoassay kit.

The following tables compare the Nichols Advantage Anti-TPO with the predicate device. NID Chemi Anti-TPO Immunoassay kit.

Similarities:

Intended Use: For the quantitative determination of Anti-TPO in human serum. ●
Both assays use recombinant TPO to bind specific Anti-TPO autoantibodies. ●
Both assays use human serum for the test sample. .
The sensitivity of both assays is sufficient to measure Anti-TPO autoantibody levels . found in patients with autoimmune disease.

Feature	Nichols Advantage™Anti-TPO	Nichols InstituteDiagnosticsChemiluminescenceAnti-TPO
Sample Size	15 uL of sample diluted with435 uL of Assay Diluent(1:30 dilution).65 uL of diluted sampleassayed.	50 uL of sample diluted with1000 uL of Assay Diluent(1:21 dilution).100 uL of diluted sampleassayed.
Calibration	Two point calibration every twoweeks (maximum) of storedworking calibration curve; orwhen controls out of range.	Full calibration curve withevery run.
Solid Phase	Streptavidin-coated magneticparticles. Streptavidin-biotinseparation technology.	6 mm bead
Incubation	30 minutes at 37°C	2 hours at room temperature
Sensitivity	0.5 IU/mL in serum	0.2 IU/mL in serum

Differences:

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Performance Characteristics:

FEATURE	Nichols AdvantageTMChemiluminescence Anti-TPO			Nichols Institute DiagnosticsChemiluminescence Anti-TPO
	Mean(IU/mL)	n	%CV	Mean(IU/mL)	n	%CV
Intra-Assay	3.4	20	5.4	2.4	21	10.7
	8.6	20	5.0	77	22	7.5
	52.9	20	3.9
Inter-Assay	Mean(IU/mL)	n	%CV	Mean(IU/mL)	n	%CV
	3.4	20	14.3	9.6	23	9.7
	8.5	20	9.6	30	10	9.1
	54.0	20	9.1
Recovery		94 - 107%		92 - 113%
Parallelism	88 - 117%			Not Done
High Dose Hook Effect		> 4,000 IU/mL		Not Done
Specificity andCross-Reactivity:
Anti-Thyroglobulin		Undetectable		Not Done
Thyroglobulin		Undetectable		Not Done
Method Comparison		Preliminary Reference Range:Normal < 2.0 IU/mL
Range of Results		0.02 - 1548		0.00 - 1783
Binomial Test Statistic		P(X) = 0.0611
Relative Sensitivity		94.1%
Relative Specificity		94.2%
Agreement	94.1%

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2098 Gaither Road

Rockville MD 20850

Food and Drug Administration

Image /page/3/Picture/2 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract image of an eagle.

OCT 1 6 1998

Mr. Jimmy Wong Manager, Clinical and Technical Affairs Nichols Institute Diagnostics 33051 Calle Aviador San Juan Capistrano, California 92675-4703

Re : K982866 Nichols Advantage™ Chemiluminescence Thyroid Trade Name: Peroxidase Autoantibodies Immunoassay Regulatory Class: II Product Code: JZO Dated: July 31,1998 Received: August 14, 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 your device can be found in the Code of Federal Requlations, 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 requlation (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 requlatory 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

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 requlation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other qeneral 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 4.0

INDICATIONS FOR USE STATEMENT

510(k) Number (if known): K982866

Device Name: Nichols Advantage™ Chemiluminescence Thyroid Peroxidase Autoantibodies Immunoassay

Indications For Use:

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
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Concurrence of CDRH, Office of Device Evaluation (ODE) -

Prescription Use ✓	OR	Over-The-Counter Use
(Per 21 CFR 801.109)		(Optional Format 1-2-96)

(Division Sign-Off)

Division of Clinical Laboratory Devices

510(k) Number ________

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).