The MESACUP TEST MPO is a semi-quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of IgG anti-myeloperoxidase (MPO) antibodies in human serum. The MESACUP TEST MPO is intended for in vitro diagnostic use as an aid in the diagnosis of certain systemic vasculitides such as microscopic polyarteritis and crescentic glomerulonephritis.

Device Description

The MESACUP Test MPO 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 myeloperoxidase antigen. Incubation allows the anti-MPO 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 MPO bound antibodies. Following another washing step, the bound enzyme-antibody conjugate is assayed by the addition of a single solution containing tetramethlybenzidine (TMB) and hydrogen peroxide (H2O2) as the chromogenic substrate. The intensity of the color generated is proportional to the serum concentration of anti-MPO antibodies. Optical density is read spectrophotometrically at 450nm. The total incubation time (at room temperature) of the assay is 150 minutes. The assay makes use of two callbrators to measure the amount of anti-MPO antibody in patient samples.

AI/ML Overview

Acceptance Criteria and Device Performance Study

The MESACUP Test MPO is an enzyme-linked immunosorbent assay (ELISA) designed for the semi-quantitative detection of IgG anti-MPO antibodies in human serum to aid in the diagnosis of certain systemic vasculitides. The device's performance was compared to a legally marketed predicate device, the Bindazyme Human Anti MPO Enzyme Immunoassay Kit (K981030).

1. Table of Acceptance Criteria and Reported Device Performance

The public summary does not explicitly state pre-defined acceptance criteria with numerical targets. Instead, it focuses on demonstrating equivalence to the predicate device. The primary performance metrics reported are clinical specificity and sensitivity.

Metric	Acceptance Criteria (Implied)	Reported MESACUP Test MPO Performance	Reported Predicate Device Performance (Bindazyme Human Anti MPO)
Clinical Specificity	Equivalent to predicate device in healthy donor serum population	100%	100%
Clinical Sensitivity	Equivalent to predicate device in vasculitis population	37%	38%
Relative Agreement	Demonstrate high agreement with predicate device	96%	- (Comparison metric)

Note: The acceptance criteria are "implied" based on the phrasing "Performance indicates that MESACUP Test MPO and the Bindazyme Human Anti MPO Enzyme Immunoassay are equivalent" and the direct comparison of performance metrics.

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

Test Set Sample Size:
- Healthy Donor Serum Population: The specific number is not provided, but the document mentions "a healthy donor serum population."
- Vasculitis Population: The specific number is not provided, but the document mentions "a vasculitis population."
Data Provenance: The studies were described as "In-house studies." This typically suggests that the studies were conducted by the manufacturer or a contracted research organization. There is no information regarding the country of origin or whether the data was retrospective or prospective.

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

This type of information is generally not applicable to an ELISA device performance study for antibody detection. The "ground truth" for ELISAs is typically established by the clinical diagnosis of the patient from whom the serum sample was taken (e.g., diagnosed with a vasculitis, or considered healthy). The diagnostic status of the patients (e.g., healthy vs. vasculitis) would have been determined by medical professionals (e.g., physicians, specialists) involved in their care, but these individuals are not functioning as "experts" establishing a ground truth for the device's output in the way a radiologist would interpret an image.

4. Adjudication Method for the Test Set

Adjudication methods (e.g., 2+1, 3+1) are typically used in studies involving subjective interpretations, such as image analysis, where multiple readers provide their opinion and discrepancies need to be resolved. This is not applicable to an objective laboratory test like an ELISA, where the result is a numerical optical density reading that is then interpreted against cutoff values.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. MRMC studies are relevant for diagnostic devices that involve human interpretation of results (e.g., imaging devices) to assess reader performance with and without AI assistance. This document describes an in vitro diagnostic (IVD) device that yields a quantitative result, not one where human readers perform a diagnostic interpretation based on the device's direct output in a way that could be "assisted" by AI.

6. Standalone (Algorithm Only) Performance

Yes, the study primarily describes the standalone performance of the MESACUP Test MPO. As an ELISA kit, it is effectively an "algorithm only" device in a laboratory setting, producing a result based on chemical reactions and optical density measurements, without requiring human "in-the-loop" interpretation beyond performing the assay and reading the result. The performance metrics (sensitivity, specificity, relative agreement) directly reflect this standalone performance.

7. Type of Ground Truth Used

The ground truth for the test samples was based on the clinical status of the patients:

"Healthy donor serum population": These samples represent individuals without the target condition, providing the ground truth for specificity.
"Vasculitis population": These samples presumably represent individuals clinically diagnosed with vasculitis, providing the ground truth for sensitivity.

Therefore, the ground truth is based on clinical diagnosis/patient case status, not pathology reports (though pathology may contribute to clinical diagnosis) or expert consensus on the device's output.

8. Sample Size for the Training Set

The document does not provide information on a specific "training set" or its sample size. For an ELISA device, the development process typically involves optimizing reagents and protocols, and establishing cutoff values, rather than training an algorithm in the way machine learning models are trained. The samples mentioned (healthy donor and vasculitis populations) are used for "in-house studies" to assess performance and likely to establish or validate cutoff values, which could be considered part of the development/validation process.

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

As noted above, the concept of a "training set" in the context of an ELISA kit is different from that of an AI algorithm. If the "in-house studies" that defined the cutoff values are considered part of a "training" or optimization phase, the ground truth would have been established by the clinical status of the patients (healthy vs. vasculitis diagnosis), similar to the test set. However, the document does not explicitly detail a separate training phase with distinct ground truth methods.

Summary

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SUMMARY OF 510(K) SAFETY AND EFFECTIVENESS MESACUP Test MPO February 27, 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 MPO is compared to a legally marketed predicate device and a substantial equivalence claim made. The predicate device is Bindazyme Human Anti MPO Enzyme Immunoassay Kit (K981030) currently manufactured and marketed by The Binding Site Ltd., Birmingham, U.K.

The intended use of the device is a semi-quantitative enzyme-linked immunosorbent assay (ELISA) for the detection of IgG anti-MPO antibodies in human serum. The MESACUP Test MPO is intended for in vitro diagnostic use as an aid in the diagnosis of certain systematic vasculitides such as microscopic polyarteritis and crescentic glomerulonephritis.

Performance indicates that MESACUP Test MPO and the Bindazyme Human Anti MPO Enzyme Immunoassay are equivalent. In-house studies indicate a clinical specificity of 100% for anti-MPO antibodies in a healthy donor serum population on both kits. Additional studies resulted a sensitivity of 37% and 38% with a vasculitis population on both assay respectively for anti-MPO antibodies. In general, the performance characteristics are comparable between the two methods (96% relative agreement).

Ylusk Robe

Yusuke Kobe Vice President Sales and Marketing Department

2/27/2004

Date

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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MAR 2 2 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

RhiGene. Inc. c/o Ms. Nanci Dexter Director of Quality and Regulatory Affairs Corgenix, Inc. 12061 Tejon Street Westminster, CO 80234 Re: K040586 Trade/Device Name: MESACUP Test MPO Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MOB Dated: February 27, 2004 Received: March 5, 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). This letter will allow you to begin marketing your device as described in your Section 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.

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This letter will allow you to begin marketing your device as described in your Section 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 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. Hackett

Joseph L. Hackett, Ph.D. Acting Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

KO40586 510(k) Number :_______________________________________________________________________________________________________________________________________________________________

Device Name: MESACUP Test MPO

Indications for Use:

The MESACUPTest MPO 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 (per 21 CFR 801.109) OR

Over-The-Couter Use

Optional Format 1-2-96)

I Reserve for Mr. Chan
Division: Div. Comd.

Division of Clinical Laboratory Devices

510(k) Number K040556

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).