This is an in vitro diagnostic test system for thedetection and Semi-quantitation of tagsesses oblic cytoplasmic antibodies in human serum This test system is to be used as an aid in the detection of antibodies associated with autoimmune vasculitis, Wegener's granulomatosis, microscopic polyarteritis, and idiopathic crescentic glomerulonephritis.

Device Description

This is an indirect fluorescent antibody test for the semi-quantitative detection of antineutrophil cytoplasmic antibody in human serum

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details based on the provided text, using the requested formatting:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria, but it establishes substantial equivalence by comparing the subject device's performance to a predicate device. The final reported performance after integrating a referee method is presented as the basis for this equivalence. Therefore, the "acceptance criteria" can be inferred from the reported performance that led to the FDA's substantial equivalence determination.

Metric	Predicate Device (NOVA Lite™ ANCA) Performance	Subject Device (Immuno Concepts ANCA) Performance	Implied Acceptance Criteria (relative to predicate)
Relative sensitivity	86.9%	98.3%	Superior or equivalent to predicate
Relative specificity	93.1%	97.7%	Superior or equivalent to predicate
Overall agreement	91.0%	98.0%	Superior or equivalent to predicate

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

The study was conducted using retrospective serum samples.

Normal Blood Donors: 497 samples (247 males, 250 females). Data provenance is not explicitly stated but implies collection from a general donor population.
Previously ANCA-Positive Samples: 383 samples. Data provenance: Reference laboratories in the USA, the United Kingdom, and Australia.

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

The document does not specify the number or qualifications of experts used to establish the ground truth for the test set. It mentions "in-house IFA assays" from reference laboratories in the USA, UK, and Australia for the previously positive samples, and the use of "referee method" (ELISA kits for MPO and PR3 antibodies) for discrepant and positive samples.

4. Adjudication Method for the Test Set

The adjudication method involved a "referee method" using ELISA kits for MPO and PR3 antibodies for samples that were:

Positive by either the subject device or predicate device in the normal blood donor group.
Discrepant between the subject device and the predicate device in the ANCA-positive sample group.

This can be considered a tertiary adjudication where an independent, more specific test is used to resolve discrepancies and confirm positivity/negativity. It's not a consensus method among human readers, but a higher-tier diagnostic test.

5. 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

This information is not applicable as the device is an in vitro diagnostic test system (indirect fluorescent antibody test) for detecting antibodies in human serum, not an AI-based imaging or diagnostic aid for human readers. No human interpretation improvement with AI is mentioned or relevant to this type of device.

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

Yes, the study describes the standalone performance of the Immuno Concepts ANCA Test System directly compared to the NOVA Lite™ ANCA predicate device. This is a "device only" performance assessment where the output is directly read and compared.

7. The Type of Ground Truth Used

The ground truth was established using:

A "referee method" based on specific antibody detection: ELISA kits for MPO (myeloperoxidase) and PR3 (proteinase 3) antibodies were used to confirm specific ANCA types in initially positive or discrepant samples. The results from these specific ELISA tests were used to reclassify samples as true positive or true negative for the final analysis.
For the "previously determined to be positive for ANCA" samples, reference laboratory IFA assay results served as an initial ground truth, which was then further adjudicated by the ELISA referee method.

8. The Sample Size for the Training Set

The document does not mention a training set as this is an in vitro diagnostic kit, not an AI/machine learning algorithm that requires training. The provided data represents a validation/verification study.

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

As no training set is mentioned or applicable, this question is not relevant to the provided document.

Summary

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K974463

Image /page/0/Picture/1 description: The image shows the logo for Immuno Concepts. The logo consists of two horizontal lines on the left, followed by the letter "I" and a symbol that looks like the number 8. To the right of these symbols is the word "Immuno" in a bold, sans-serif font, stacked on top of the word "concepts" in a similar font.

FEB - 9 1998

Date Prepared: November 24, 1997 Contact Person: Eric S. Hoy, Ph.D. Name of Device:

Trade Name Immuno Concepts Antineutrophil Cytoplasmic Antibody Test System with Formalin Fixed Human Neutrophils
· Common Name Immuno Concepts ANCA Test System with Formalin Fixed Human Neutrophils
· Classification Name Antineutrophil Cytoplasmic Antibody (21 CFR 866.5660)

Legally marketed device with which this device has been shown to be equivalent: NOVA Lite™ ANCA, INOVA Diagnostics, San Diego, CA, K961340

Description:

This is an indirect fluorescent antibody test for the semi-quantitative detection of antineutrophil cytoplasmic antibody in human serum

Intended Use:

This test system is for in vitro diagnostic use for the detection in antibody in
human serum. This test system is to be used as a aid in the sescotated with glomerulonephritis.

Summary of Technological Characteristics Compared to the Predicate Device: Both the predicate device and this device are fluorescent antibody tests for the detection of antineutrophil cytoplasmic antibody in human serum.

Description of Laboratory Data That Indicate Substantial Equivalence: Serum Samples Obtained from Normal Blood Donors

Serum samples from 497 blood donors (247 males and 250 females) were tested using the subject device and the predicate device. The results of this comparison are shown in the following Table:

	Predicate Device
	Positive	Negative
Immuno Concepts ANCA	Positive	5	9
	Negative	37	446

The relatively high number of ANCA positive samples in these otherwise normal individuals was troubling, so we tested all positive sera for antibodies to MPO and PR3 using ELISA kits obtained from elias usa, inc. Among the IFA positive samples, none were found to be positive for MPO or PR3 antibodies. The samples that were IFA positive on both the predicate device and the subject device were considered true positives for the comparison of the IFA kits. The remaining samples were considered to be false positives on the respective assays. Thus, when the referee method is taken into account, the comparisons look like this:

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Reference Method
	Positive	Negative
	Positive	5	9
Immuno Concepts ANCA	Negative	0	483

Serum Samples Previously Determined to be Positive for ANCA by Indirect Immunofluorescence

Serum samples which had been judged to be positive for ANCA using in-house IFA assays were obtained from reference laboratories in the USA, the United Kingdom, and Australia. A total of 383 sera, which we expected to be positive for ANCA, were examined in this part of the study. These samples were tested on the predicate device and the subject device with the following results:

		Predicate Device
	Positive	Positive	Negative
Immuno Concepts ANCA	Positive	250	43+
	Negative	8	82

The discrepant samples were tested for MPO and PR3 antibodies by ELISA. When this referee method was taken into account, the comparisons showed the following data:

	Reference Method
	Positive	Negative
Immuno Concepts ANCA	288	4
	5	86
	Reference Method
	Positive	Negative
NOVA Lite™ ANCA	254	3
	39	87

Combining the data from the normal blood donor population and the expected positive samples, we obtained the following data on the initial comparison of the subject device and the predicate device:

		Predicate Device
		Positive	Negative
Immuno Concepts ANCA	Positive	255	52
Immuno Concepts ANCA	Negative	45	528

Relative sensitivity : 85% Relative specificity: 91% Overall agreement: 89%

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Taking into account the results of the specific MPO and PR-3 testing, the two tests yield the following data:

		Reference Method
		Positive	Negative
Immuno Concepts ANCA	Positive	293	13
	Negative	5	569
		Reference Method
		Positive	Negative
NOVA Lite™ ANCA	Positive	259	40
	Negative	39	542

For NOVA Lite™ ANCA: For Immuno Concepts ANCA: Relative sensitivity : 86.9% Relative sensitivity : 98.3% Relative specificity: 93.1% Relative specificity: 97.7% Overall agreement: 91.0% Overall agreement: 98.0%

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/3/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle symbol on the right and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion on the left. The eagle symbol is composed of three curved lines that resemble the wings and body of an eagle. The text is written in a simple, sans-serif font.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Eric S. Hoy, Ph.D. Chief Scientific Officer Immuno Concepts Incorporated 9779 "I" Business Park Drive Sacramento, California 95827

FEB - 9 1998

Re : K974463 Immuno Concepts ANCA Test System with Formalin Trade Name: Fixed Human Neutrophils Regulatory Class: II Product Code: мов Dated: November 24, 1997 November 26, 1997 Received:

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 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 requirement, 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 Failure to comply with the GMP regulation may result in assumptions. 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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/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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Page of

510(k) Number (if known): K974463

Device Name: Immuno Concepts ANCA Test System with Formalin Fixed Human Neutrophils

Indications For Use:

(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

510(k) Number ___________

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

Regulation Number and Section

§ 866.5660 Multiple autoantibodies immunological test system.

(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).