The Varelisa® RNP Antibodies EIA kit is designed for the semiquantitative and qualitative determination of RNP antibodies in serum or plasma to aid in the diagnosis of Systemic Lupus Erythematosus (SLE) and Mixed Connective Tissue Disease (MCTD).

Device Description

The Varelisa RNP Antibodies is an enzyme immunoassay for the semiquantitative and qualitative determination of RNP antibodies in serum or plasma. The determination of RNP antibodies is of central importance for the clinical diagnosis rheumatic autoimmune diseases. The presence of RNP antibodies suggests the possibility of Systemic Lupus Erythematosus (SLE) and Mixed Connective Tissue Diseases (MCTD). The Varelisa RNP Antibodies is an indirect noncompetitive enzyme immunoassay. The wells of a microplate are coated with human recombinant RNP (68 kDa, A, C) antigens. Antibodies specific for RNP present in a patient sample bind to this antigen. In a second step an enzyme labeled second antibody (Conjugate) binds to the antigenantibody complex which leads to the formation of an enzyme labeled antigen-antibody sandwich 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.

AI/ML Overview

Here's an analysis of the provided text regarding the Varelisa® RNP Antibodies device, structured to address your specific questions.

1. Table of Acceptance Criteria and Reported Device Performance

The provided text describes a "Laboratory Equivalence" study rather than a traditional acceptance criteria study with predefined thresholds. The goal was to demonstrate substantial equivalence to a predicate device.

Acceptance Criteria (Implied/Study Design)	Reported Device Performance
High overall agreement with predicate device (Synelisa™ U1-snRNP Antibodies).	92% overall agreement with predicate, excluding 8 samples where a different result was expected.
Blood donor samples to be negative in both assays.	All blood donor samples (N/A, but implied within the 70 samples) were found negative in both assays.

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

Sample Size for Test Set: 70 samples (including 20 apparently healthy blood donors).
Data Provenance: Not explicitly stated, but it's a "Laboratory Equivalence" study comparing two in-vitro diagnostic assays. The context implies the samples were human serum or plasma. It is not specified if the samples were retrospective or prospective, or the country of origin.

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

Not applicable. The "ground truth" for this comparative study was the result obtained from the predicate device (Synelisa™ U1-snRNP Antibodies), not an independent expert assessment. The study aimed to demonstrate agreement between the new device and an existing, legally marketed device.

4. Adjudication Method for the Test Set

Not applicable. There was no explicit adjudication method described. The comparison was directly between the results of the new device and the predicate device. For some omitted samples, the discrepancies were explained by the compositional differences of the assays (e.g., presence of RNP A and C in the new device, but not in the predicate).

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

Not applicable. This is an in-vitro diagnostic device (an immunoassay) and the submission refers to the device itself, not AI assistance for human readers.

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

Yes, this study represents a standalone performance evaluation of the Varelisa® RNP Antibodies immunoassay. Its performance was compared directly to the predicate device without human interpretation or intervention as part of the primary measurement.

7. The Type of Ground Truth Used

The "ground truth" for the purpose of the substantial equivalence study was the results obtained from the predicate device (Synelisa™ U1-snRNP Antibodies). This is a common approach for demonstrating equivalence for IVD devices aiming for a 510(k) clearance. Clinical diagnosis (SLE and MCTD) is the ultimate clinical outcome, but for this specific regulatory submission, the predicate device's results served as the reference.

8. The Sample Size for the Training Set

Not applicable. This is an immunoassay kit, not a machine learning model, so there is no "training set" in the context of algorithm development.

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

Not applicable. There is no training set for this type of device.

Summary

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510(K) SUMMARY OF SAFETY AND EFFECTIVENESS 9.

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.

DOV 26 1999

Assigned 510(k) Number:	K993589
Date of Summary Preparation:	October 12, 1999
Distributor:	Pharmacia & UpjohnDiagnostics Division, US Operation7425-248-17000 Portage RoadKalamazoo, MI 49001
Manufacturer:	Pharmacia & Upjohn Diagnostics GmbH & Co. KGMunzingerstrasse 7D-79111 Freiburg, Germany
Company Contact Person:	Karen E.MatisManager, Regulatory Affairs and QualityManagementDiagnostics DivisionUS Operation7000 Portage Road7425-248-01Kalamazoo, MI 49001(614) 794-3324 (Phone)(614) 794-0266 (Fax)
Device Name:	Varelisa® RNP Antibodies
Common Name:	Antinuclear antibody immunological test

Product Name	Product Code	Class	CFR
Varelisa® RNP Antibodies	82LJM	II	866.5510

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Substantial Equivalence to:

Synelisa™ U1-snRNP Antibodies

Intended Use Statement:

General Description of the Device

The Varelisa RNP Antibodies is an enzyme immunoassay for the semiquantitative and qualitative determination of RNP antibodies in serum or plasma.

The determination of RNP antibodies is of central importance for the clinical diagnosis rheumatic autoimmune diseases. The presence of RNP antibodies suggests the possibility of Systemic Lupus Erythematosus (SLE) and Mixed Connective Tissue Diseases (MCTD).

Varelisa® RNP Antibodies Test Principle

The Varelisa RNP Antibodies is an indirect noncompetitive enzyme immunoassay. The wells of a microplate are coated with human recombinant RNP (68 kDa, A, C) antigens. Antibodies specific for RNP present in a patient sample bind to this antigen.

In a second step an enzyme labeled second antibody (Conjugate) binds to the antigenantibody complex which leads to the formation of an enzyme labeled antigen-antibody sandwich 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.

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Device Comparison:

Synelisa® U1-snRNP (68 kDa) Antibodies (the predicate device) and Varelisa® RNP Antibodies Assay (the new device) are both indirect noncompetitive enzyme immunoassays for the determination of RNP antibodies in serum or plasma to aid in the diagnosis of Systemic Lupus Erythematosus (SLE) and Mixed Connective Tissue Disease (MCTD).

The essential difference between the two assays is the inclusion of the recombinant RNP A and RNP C proteins in addition to the RNP (68 kDa) protein in the antigen mixture of the new device. The new device now includes the three major antigens of the U1-RNP complex.

Laboratory Equivalence

70 samples including 20 apparently healthy blood donors were tested. Excluding 8 samples for which a different result was expected, the overall agreement was 92%. 5 of the omitted samples were found to be equivocal in Varelisa RNP Antibodies (for Synelisa U1-snRNP (68kDa) Antibodies, no equivocal range is defined). The other 3 omitted samples were shown to contain antibodies directed against the RNP proteins A and C. Since the Synelisa U1-snRNP (68kDa) does not contain RNP A and C, antibodies directed against these antigens can only be detected by the Varelisa RNP Antibodies assav.

The blood donor samples were all found negative in both assays.

These results demonstrate an excellent agreement between both assays.

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Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features the department's name in a circular arrangement around a symbol. The symbol consists of four stylized lines that resemble a caduceus, a traditional symbol of medicine and healthcare. The overall design is simple and professional, reflecting the department's role in public health and human services.

NOV 26 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Karen E. Matis Manager, Regulatory Affairs and Ouality Management Pharmacia & Upjohn 7000 Portage Road Kalamazoo, Michigan 49001-0199

K993589 Trade Name: Varelisa® RNP Antibodies Regulatory Class: II Product Code: LKO Dated: October 20, 1999 Received: October 22, 1999

Dear Ms. Matis:

Re:

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 at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Autman

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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510(k) Number: _ _ K 99 3589

Device Name: Varelisa® RNP Antibodies

The Varelisa RNP Antibodies EIA kit is designed for the semiguantitative and qualitative determination of RNP antibodies in serum or plasma to aid in the diagnosis of Systemic Lupus Erythematosus (SLE) and Mixed Connective Tissue Disease (MCTD).

Anton S. Maefri

n Sign-Off) on of Clinical Laboratory Devices 16993589

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use

Over-The-Counter Use

(Per 21 CFR 801.109)

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).