The Varelisa PR3 ANCA EIA kit is designed for the semi-quantitative and qualitative determination of proteinase 3 anti neutrophil cytoplasmic antibodies (PR3 ANCA) in human serum or plasma to aid in the diagnosis of Wegener's granulomatosis.

Device Description

Varelisa PR3 ANCA is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of PR3 ANCA in human serum or plasma. The test kit contains microplate strips coated with human purified PR3 antigen, calibrators, positive and negative controls, enzyme-labeled conjugate, substrate and substrate stop solution, sample diluent and wash buffer.

AI/ML Overview

Here's an analysis of the provided text to extract the requested information about acceptance criteria and the study proving device performance:

1. Table of Acceptance Criteria and Reported Device Performance:

The document describes the device, its intended use, and its comparison to a predicate device. However, it does not explicitly state acceptance criteria in the form of specific performance metrics (e.g., sensitivity, specificity thresholds) that the new device (Varelisa PR3 ANCA) needed to meet.

Instead, the study's goal was to demonstrate substantial equivalence to the predicate device (INOVA QUANTA Lite™ PR-3) and that it "performs as expected from the medical literature" and "according to state-of-the-art expectations." The evaluation was based on a comparative study.

Therefore, the table will reflect this comparative nature rather than explicit acceptance criteria.

Acceptance Criteria (Implied)	Reported Device Performance
Substantial equivalence to the predicate device (INOVA QUANTA Lite™ PR-3)	Demonstrated comparability through:
- Comparison study analyzing positive, equivocal, and negative sera	- Data show comparability in results for positive, equivocal, and negative sera with the predicate.
- Results obtained for externally defined Calibrators and clinically defined sera	- Data show comparability in results for externally defined calibrators and clinically defined sera with the predicate.
- Results obtained for samples from apparently healthy subjects (normal population)	- Data show expected results for samples from apparently healthy subjects.
Performance according to state-of-the-art expectations and medical literature	"the assay performs as expected from the medical literature" and "performs according to state-of-the-art expectations."

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

Sample Size for Test Set: Not explicitly stated in the provided text. The document mentions a "data set including results obtained within a comparison study analyzing positive, equivocal and negative sera," and "results obtained for externally defined Calibrators and clinically defined sera," and "results obtained for samples from apparently healthy subjects (normal population)." However, the exact number of samples for each category or overall is not provided.
Data Provenance: Not explicitly stated (e.g., country of origin). The study is described as a "comparison study," which implies prospective collection for the purpose of the study. However, it's not definitively stated as retrospective or prospective, though the nature of comparing performance against an existing device suggests a concurrent, prospective analysis of samples.

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.

4. Adjudication Method for the Test Set:

Adjudication Method: Not mentioned. The process of establishing "clinically defined sera" or the determination of "positive, equivocal and negative sera" is not detailed.

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

MRMC Study: No. This study is an in-vitro diagnostic (IVD) assay comparison, not a multi-reader, multi-case study involving human readers interpreting images or data.

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

Standalone Performance: Yes, in essence. The Varelisa PR3 ANCA is an automated in-vitro diagnostic (IVD) immunoassay kit. Its performance is evaluated directly based on its output (semi-quantitative and qualitative determination of PR3 ANCA) from human serum or plasma samples. There is no "human-in-the-loop" component in the performance of the device itself (though human laboratory personnel would run the test). The "algorithm" here is the biochemical reaction and detection system of the EIA.

7. The Type of Ground Truth Used:

The ground truth appears to be based on:

Clinical Definition/Established Clinical States: "clinically defined sera." This likely refers to samples from patients with confirmed diagnoses of Wegener's granulomatosis (positive) and other relevant conditions or healthy controls (negative/equivocal).
Predicate Device Results: The comparison study likely used the predicate device's results as a reference point for agreement for positive, equivocal, and negative sera.
External Calibrators: Used to establish reference points within the assay itself.
Medical Literature: Performance is deemed "as expected from the medical literature," implying existing knowledge about PR3 ANCA levels and their correlation with disease.

8. The Sample Size for the Training Set:

Training Set Sample Size: Not applicable/not mentioned. This is an immunoassay kit, not a machine learning algorithm that requires a "training set" in the traditional sense. The device's components (antigen, controls, calibrators) are designed and manufactured based on biochemical principles rather than trained on a dataset.

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

Ground Truth for Training: Not applicable. As noted above, this is not a machine learning model where a training set with established ground truth is used to train an algorithm. The "ground" for the development of such an IVD kit would be the established biochemical understanding of antigen-antibody interactions and the clinical relevance of PR3 ANCA.

Summary

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510(K) SUMMARY OF SAFETY AND 9. EFFECTIVENESS

This summary of safety and effectiveness information is being submitted in accordance with the requirements of The Safety Medical Devices Act of 1990 (SMDA 1990) and 21 CFR Part 807.92.

Assigned 510(k) Number:	K041043
Date of Summary Preparation:	April 20, 2004
Manufacturer:	Pharmacia Deutschland GmbH,Diagnostics DivisionMunzinger Strasse 7D-79111 Freiburg, Germany
Company Contact Person:	Michael LinssManager, Compliance and QualityPharmacia Deutschland GmbHDiagnostics DivisionMunzinger Strasse 7D-79111 Freiburg, Germany+49-761-47805-310(Phone)+49-761-47805-335 (Fax)
Device Name:	Varelisa PR3 ANCA
Common Name:	test system, antineutrophil cytoplasmicantibodies (anca)
Classification

Classification

Product Name	Product Code	Class	CFR
Varelisa PR3 ANCA	MOB	II	866.5660

Substantial Equivalence to

INOVA QUANTA Lite™ PR-3

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Intended Use Statement

General Description of the Device

Varelisa PR3 ANCA is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of PR3 ANCA in human serum or plasma.

The test kit contains microplate strips coated with human purified PR3 antigen, calibrators, positive and negative controls, enzyme-labeled conjugate, substrate and substrate stop solution, sample diluent and wash buffer.

Varelisa® PR3 ANCA Test Principle

Varelisa PR3 ANCA is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of PR3 ANCA in human serum or plasma. The wells of a microplate are coated with human PR3 antigen, Antibodies specific for PR3 present in the patient sample bind to the antigen.

In a second step the enzyme labeled second antibody (conjugate) binds to the antigen-antibody complex which leads to the formation of an enzyme labeled conjugate-antibody-antigen complex. The enzyme labeled antigen-antibody complex converts the added substrate to form a colored solution.

The rate of color formation from the chromogen is a function of the amount of conjugate complexed with the bound antibody and thus is proportional to the initial concentration of the respective antibodies in the patient sample.

Device Comparison

Both assays (the predicate and the new device) are indirect noncompetitive enzyme immunoassays for the semi-quantitative and qualitative determination of IgG autoantibodies to protease 3 (PR3) in human serum. Both assays recommend the same sample dilutions and use comparable enzyme-linked conjugates and antigens. Based on currently available data from the literature the measuring of the autoantibodies to PR3 provides aid in the diagnosis of Wegener's granulomatosis.

A difference between both assays is that the INOVA QUANTA Lite™ PR-3 is only recommended for use in serum specimen while the PHARMACIA Varelisa PR3 ANCA is intended for use with serum and plasma. The cut-off in the INOVA QUANTA Lite™ PR-3 is evaluated by using a low and a high positive Standard and a grading of the results in negative, weak, moderate and strong positive. The PHARMACIA Varelisa PR3 ANCA uses a set of six Calibrators and classifies the results as negative, equivocal and positive.

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Laboratory equivalence

The comparability of QUANTA Lite™ PR-3 and Varelisa PR3 ANCA is supported by a data set including

· results obtained within a comparison study analyzing positive, equivocal and negative sera.
· results obtained for externally defined Calibrators and clinically defined sera.
results obtained for samples from apparently healthy subjects (normal population).

The data show that the assay performs as expected from the medical literature.

In summary, all available data support that the new device, PHARMACIA Varelisa PR3 ANCA is substantially equivalent to the predicate device, INOVA QUANTA Lite™ PR-3, and that the new device performs according to state-ofthe-art expectations.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its body and wings. The logo is surrounded by text that reads "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" in a circular arrangement.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL - 2 2004

Mr. Michael Linss Manager, Compliance and Quality Pharmacia Deutschland GmgH Diagnostics Division Munzinger Strasse 7 D-79111 Freiburg, Germany

K041043 Re: Trade/Device Name: Varelisa® PR3 ANCA Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MOB Dated: April 20, 2004 Received: April 23, 2004

Dear Mr. Linss:

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

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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,

Robert L. Becker, Jr.

Robert L. Becker, Jr., M.D., Ph. 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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Varelisa® PR3 ANCA - New Device 510(k) Submission Section 1. Indications for Use Statement

510(k) Number: _______________________________________________________________________________________________________________________________________________________________

Device Name: Varelisa® PR3 ANCA

Intended Use Statement

The Varelisa PR3 ANCA EIA kit is designed for the semiquantitative and qualitative The Varensa FRS ANCA Elli neutrophil cytoplasmic antibodies (PR3 ANCA) in human serum or protemase -> and notal of Wegener's granulomatosis.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use	✓
(Per 21 CFR 801.109)
	OR
	Over-The-Counter Use
Thane Chan
	Division Sign-Off
Office of In Vitro Diagnostic Device

Evaluation and Safety

510(k)________________________________________________________________________________________________________________________________________________________________________

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).