This is an enzyme immunoassay test system for the detection of antinuclear antibodies in human serum. This test system is to be used as an aid in the detection of antibodies associated with systemic rheumatic disease.

Device Description

This is an enzyme immunoassay for the detection of antinuclear antibodies in human serum.

AI/ML Overview

This document describes the RELISA® ANA Screening Test System, an enzyme immunoassay for the detection of antinuclear antibodies in human serum, intended as an aid in detecting antibodies associated with systemic rheumatic disease.

1. Acceptance Criteria and Reported Device Performance:

The primary acceptance criterion appears to be "overall agreement" with a reference method. The initial comparison to the predicate device set the stage, but a "referee method" (Immuno Concepts HEp-2000® ANA-Ro Test System using indirect fluorescent antibody technique) was ultimately used to clarify "false positive" and "false negative" results.

Acceptance Criterion	Reported Device Performance (Revised with Referee Method)
Overall Agreement	93.5%

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

Sample Size:
- Initial Comparison (with Predicate device): 214 (Positive) + 46 (Predicate Negative/Test Positive) + 12 (Predicate Positive/Test Borderline) + 105 (Predicate Negative/Test Borderline) + 8 (Predicate Positive/Test Negative) + 787 (Negative) = 1172 samples.
- Revised Comparison (with Referee Method): The number of samples re-evaluated for the "referee method" was 79 "false positive" (from the initial comparison) and 4 "false negative" samples. The table provided for the revised comparison then summarizes the results for the entire cohort of 1172 samples based on the referee method's classification for the previously discrepant cases.
Data Provenance: Not explicitly stated, but given context of the submission, it is assumed to be retrospective clinical samples. No country of origin is mentioned.

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

Number of Experts: Not explicitly stated.
Qualifications of Experts: The ground truth for the referee method involved use of the "indirect fluorescent antibody technique" and observation of "clearly discernible ANA patterns." This strongly implies interpretation by trained laboratory professionals, likely medical technologists or clinical immunologists with expertise in ANA testing. Specific qualifications (e.g., years of experience, board certification) are not provided.

4. Adjudication Method for the Test Set:

Adjudication Method: The document describes a specific process for adjudication of discrepant results: "The large number of 'false positive' samples seen with the Immuno Concepts test was troubling, so we tested all of these sera for antinuclear antibodies using Immuno Concepts HEp-2000® ANA-Ro Test System (K944096 & K972145)." This indicates a targeted re-evaluation of initially discrepant samples using a more definitive "referee method" (indirect fluorescent antibody technique), where the results of this referee method were then considered the "true" classification. This is a form of discrepancy resolution with a gold standard.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

There is no indication of an MRMC comparative effectiveness study being performed. The study focuses on comparing the new device against a predicate device and a "referee method," not on human reader performance with or without AI assistance.

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

Yes, a standalone performance study was conducted. The RELISA® ANA Screening Test System is an enzyme immunoassay, and its performance was evaluated directly against other laboratory tests (the predicate device and the indirect fluorescent antibody technique) without explicit human intervention in the interpretation of the RELISA results for the purpose of the study. The results are from the device itself.

7. The Type of Ground Truth Used:

The initial comparison used the predicate device's results as a reference.
The refined comparison, which led to the final performance metrics, used the indirect fluorescent antibody technique (IFA) performed with the Immuno Concepts HEp-2000® ANA-Ro Test System as the "referee method" or gold standard for establishing ground truth, especially for discrepant samples. IFA is generally considered a highly sensitive and specific method for ANA detection and pattern recognition, often serving as a reference method in clinical immunology.

8. The Sample Size for the Training Set:

The document does not explicitly mention a separate training set or its sample size. This type of submission for an in vitro diagnostic (IVD) device typically focuses on clinical validation (test set) for regulatory approval rather than machine learning model training.

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

As no training set is explicitly described, there is no information provided on how its ground truth might have been established.

Summary

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KG92041

Image /page/0/Picture/2 description: The image shows the logo for Immuno Concepts. The logo consists of a stylized "IC" symbol followed by the word "immuno" in a bold, sans-serif font. Below "immuno" is the word "concepts" in a smaller, bold, sans-serif font. The logo is black and white.

510(k) SUMMARY *

Date Prepared: July 12, 1999 Contact Person: Eric S. Hoy, Ph.D., SI(ASCP) Name of Device:

· Trade Name RELISA® ANA Screening Test System
Common Name Antinuclear Antibody Enzyme Immunoassay Test System
· Classification Name Antinuclear Antibody (21 CFR 866.5100)

Legally marketed device with which this device has been shown to be equivalent: Enzyme Immunoassay Antinuclear Antibody Screening Test Kit manufactured by Helix Diagnostics, West Sacramento, CA, K954723.

Description:

This is an enzyme immunoassay for the detection of antinuclear antibodies in human serum.

Intended Use:

Summary of Technological Characteristics Compared to the Predicate Device:

Technologically, this device is similar to the predicate device with the following exceptions:

The predicate device has all 96 microwells sealed in a single pouch. a) After this pouch is opened, the wells remain stable for only 30 days. The present device has each eight well strip of microwells sealed in an individual pouch, so that unused wells remain in the pouches, and maintain at least 12 months stability.

b) The predicate device uses a cutoff control serum, the present device uses a calibrator serum in the kit.

Description of Laboratory Data That Indicate Substantial Equivalence:

For direct determination of relative sensitivity and specificity, we used the Enzyme Immunoassay Antinuclear Antibody Screening Test Kit manufactured by Helix Diagnostics, West Sacramento, CA, (K954723) as a reference method. The data obtained in this comparison are shown in the following Table.

Helix Diagnostics Enzyme Immunoassay AntinuclearAntibody Screening Test		Positive	Negative
Immuno ConceptsRELISA® AntinuclearAntibody Test	Positive	214	46
	Borderline	12	105
	Negative	8	787

Borderline results were considered positive. These data show an overall agreement of 85.4%

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The large number of "false positive" samples seen with the Immuno Concepts test was troubling, so we tested all of these sera for antinuclear antibodies using Immuno Concepts HEp-2000® ANA-Ro Test System (K944096 & K972145). Seventy-nine of the "false positive" samples were shown to have clearly discernible ANA patterns with the indirect fluorescent antibody technique and were considered "true positives" for the detection of antinuclear antibodies. Four of the "false negative" samples were shown to be negative by the indirect fluorescent antibody technique and were considered "true negatives" for the detection of antinuclear antibodies. Thus, when the referee method is taken into account, the comparison looks like this:

		ReferencePositive	MethodNegative
Immuno ConceptsRELISA° AntinuclearAntibody Test	Positive	305	72
	Negative	4	791

These data show an overall agreement of 93.5%

In accordance with 21 CFR 807.92(b)(3), we conclude from these data that the present device is substantially equivalent to the predicate device.

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Image /page/2/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized image of three human profiles facing right, stacked on top of each other. The profiles are connected by flowing lines that resemble waves or fabric. The image is surrounded by a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" written around it.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 23 1999

Eric S. Hoy, Ph.D., SI (ASCP) Chief Scientific Officer Regulatory Affairs Immuno Concepts, N.A., Limited 2280 Springlake Road, Suite 106 Dallas, Texas 75234

Re: K992041

Trade Name: RELISA® ANA Screening Test System Regulatory Class: II Product Code: LJM Dated: June 15, 1999 Received: June 17, 1999

Dear Dr. Hoy:

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 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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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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K992041 510(k) number (if known):

Device Name: RELISA® ANA Screening Test System

Indications for use:

. .

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

イン

Peter E. Machon

vision Sign-Off) of Clinical Laboratory Devices

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________

Regulation Number and Section

§ 866.5100 Antinuclear antibody immunological test system.

(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).