MESACUP TEST PR-3 by RHIGENE, INC.

The MESACUP TEST PR-3 is a semi-quantitative, enzyme-linked immunosorbent assay (ELISA) for the detection of IgG anti-proteinase III (PR-3) antibodies in human serum. The MESACUP TEST PR-3 is intended for in vitro diagnostic use as an aid in the diagnosis of certain systemic vasculitides such as Wegener's granulomatosis.

Device Description

The MESACUP Test PR-3 is an enzyme-linked immunosorbent assay (ELISA), utilizing the 96-microwell plate format, similar to the predicate device. Diluted serum samples, calibrator sera, and controls are incubated in microwells coated with proteinase III antigen. Incubation allows the anti-PR-3 antibodies present in the samples to react with the immobilized antigen. After the removal of unbound serum proteins by washing, antibodies specific for human IgG immunoglobulins, labeled with horseradish peroxidase (HRP), are added forming complexes with the PR-3 bound antibodies. Following another washing step, The bound enzyme-antibody conjugate is assayed by the addition of a single solution containing tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) as the chromogenic substrate, The intensity of the color generated is proportional to the serum concentration of anti-PR-3 antibodies, Optical density is read spectrophotometrically at 450mm. The total incubation time (at room temperature) of the assay is 150 minutes. The assay makes use of two calibrators to measure the amount of anti-PR-3 antibody in patient samples.

AI/ML Overview

The provided text describes the MESACUP Test PR-3, an ELISA device for detecting IgG anti-proteinase III (PR-3) antibodies. The information focuses on its substantial equivalence to a predicate device and its intended use, rather than explicit acceptance criteria with pre-defined thresholds. However, we can infer performance metrics and the study details based on the provided summary.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Since explicit numerical acceptance criteria (e.g., "Sensitivity must be >= 90%") are not stated, we can infer the implicit acceptance criterion was "performance equivalent to the predicate device."

Metric	Acceptance Criteria (Implied)	Reported Device Performance (MESACUP Test PR-3)	Reported Predicate Device Performance (Bindazyme Human Anti-PR3 Enzyme Immunoassay)
Clinical Specificity	100% (in healthy donor serum population)	100%	100%
Sensitivity (Vasculitis Population vs. IIF ANCA positive)	~35% (based on predicate performance)	35%	35%
Sensitivity (cANCA positive IIF patterns)	~87% (based on predicate performance)	87%	87%
Relative Agreement	100% with predicate device	100%	N/A (this is a comparison metric)

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

Test Set Sample Size: Not explicitly stated. The document mentions "a healthy donor serum population" and "a vasculitis population," but no numbers are provided for either group.
Data Provenance: "In-house studies." The country of origin is not specified, but the applicant's address is in Des Plaines, IL, USA. The studies are retrospective as they are testing existing samples to determine performance characteristics.

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

Number of Experts: Not mentioned.
Qualifications of Experts: Not mentioned. The ground truth appears to be based on the clinical diagnosis (healthy vs. vasculitis) and other diagnostic methods (IIF ANCA positive results, cANCA positive IIF patterns), but who made these determinations is not specified.

4. Adjudication Method for the Test Set

No adjudication method is mentioned for establishing the ground truth. The text implies a pre-existing classification of samples (e.g., "healthy donor serum population," "vasculitis population," "IIF ANCA positive results," "cANCA positive IIF patterns").

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 device is an In Vitro Diagnostic (IVD) assay, not an AI-powered diagnostic imaging device that involves human readers. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

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

Yes, this is an ELISA (Enzyme-Linked Immunosorbent Assay), which is a standalone laboratory test. Its performance is measured directly without human interpretation of its output in the same way an imaging algorithm's output would be interpreted. The "algorithm" here refers to the biochemical process of the assay itself, and its result (optical density) is read spectrophotometrically.

7. The Type of Ground Truth Used

The ground truth appears to be a combination of:
- Clinical diagnosis: Healthy individuals vs. patients with vasculitis (specifically Wegener's granulomatosis).
- Reference laboratory tests: Immunofluorescence (IIF) ANCA positive results and cANCA positive IIF patterns.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set." This type of IVD typically undergoes development and optimization, but the term "training set" is more commonly associated with machine learning algorithms. The performance data presented is likely from a validation or test set.

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

As no "training set" is explicitly mentioned for this IVD, the method for establishing its ground truth is not detailed. For typical IVD development, calibration and controls are used, and the assay design itself is based on known biochemical interactions.

Summary

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SUMMARY OF 510(K) SAFETY AND EFFECTIVENESS MESACUP Test PR-3 March 30, 2004

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 MESACUP Test PR-3 is compared to a legally marketed predicate device and a substantial equivalence claim made. The predicate device is Bindazyne Human Anti-PR3 Enzyme Inutumoassay Kit (K981029) currently manufactured and marketed by The Binding Site Ltd., Birmingham, U.K.

The MESACUP Test PR-3 is an enzyme-linked inununosorbent assay (ELISA), utilizing the 96-microwell plate format, similar to the predicate device. Diluted serum samples, calibrator sera, and controls are incubated in microwells coated with proteinase III antigen. Incubation allows the anti-PR-3 antibodies present in the samples to react with the immobilized antigen. After the removal of unbound serum proteins by washing, antibodies specific for haman IgG immunoglobulins. labeled with horseradish peroxidase (HRP), are added forming complexes with the PR-3 bound antibodics. Following another washing step. The bound enzyme-antibody conjugate is assayed by the addition of a single solution containing tetramethlybenzioine (TMB) and lydrogen peroxide (H2O2) as the chromogenic substrate, The intensity of the color generated is proportional to the scrum concentration of anti-PR-3 antibodies, Optical density is read spectrophotometrically at 450mm. The total incubation time (at toom The assay makes use of two calibrators to measure the amount tomperature) of the assav is 150 minutes. of anti-PR-3 antibody in patient samples.

The intended use of the device is a somi-quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of IgG anti-proteinase III (PR-3) antibodies in human serum. The MESACUP Test PR-3 is intended for in vitro diagnostic use as an aid in the diagnosis of certain systematic vasculitides such as Wegence's granulomatosis.

Performance indicates that MESACUP Test PR-3 and the Bindazyme Human Anti-PR3 Enzyme Immunoassay are equivalent. In-house studies indicate a clinical specificity of 100% for anti-PR-3 antibodies in a healthy donor serum population on both kits. Additional studies resulted a sensitivity of 35% with a vasculitis population on both assay for anti-PR-3 antibadies compared to IIF ANCA positive results and 87% for both assays specifically for cANCA positive IIF petterns. In general, the performance characteristics are comparable between the two methods (100% relative agreement).

Yuck Robe

Yusuke Kobe Vice President, Sales and Marketing Department

3/30/2004

Date

Fax:

455 State St. Ste 104 (847) 375-9093

Des Plaines, IL 80016

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/1/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized graphic of an abstract human figure with three flowing lines, positioned to the right of the text. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the graphic.

APR - 2 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Nanci Dexter Director of Quality/ Regulatory Affairs RhiGene, Inc. c/o Corgenix, Inc. 12061 Tejon St. Westminister, CO 80234

K040711 Re:

Trade/Device Name: MESACUP TEST PR-3 Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MOB Dated: March 10, 2004 Received: March 18, 2004

Dear Ms. Dexter:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. 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 (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Joseph L. Aralett

Joseph L. Hackett, Ph.D. Acting 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 Statement

510(k) Number: K040711

Device Name: MESACUP TEST PR-3 Indications for Use:

The MESACUP TEST PR-3 is intended to be used by clinical (hospital and reference) laboratories.

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

Prescription Use V (per 21 CFR 801.109)

Over-The-Couter Use_

Optional Format 1-2-96)

Maria Chan
Division Sign Off

ivision Sian

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K040711

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).