The Varelisa ReCombi ANA Profile EIA kit is designed for the qualitative determination of eight antinuclear antibodies in human serum or plasma to aid in the diagnosis of systemic rheumatic diseases such as SLE (Systemic Lupus Erythematosus), Scleroderma (Progressive Systemic Sclerosis), MCTD (Mixed Connective Tissue Disease), SS (Sjögren's Syndrome) and Polymyositis/ Dermatomyositis. The Varelisa ReCombi ANA Profile individually detects antibodies against dsDNA, RNP(68 kDa, A, C), Sm(B,B',D) SS-A/Ro(52 kDa, 60 kDa), SS-B/La, Scl-70, Centromere and Jo-1.

Device Description

The Varelisa ReCombi ANA Profile is an enzyme immunoassay for the individual qualitative determination of 8 antinuclear antibodies in serum or plasma.

AI/ML Overview

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for substantial equivalence of the Varelisa ReCombi ANA Profile to its predicate devices specifically relate to a high degree of correlation in the results.

Acceptance Criteria (Implicit)	Reported Device Performance
High degree of correlation between new device and predicate devices.	Overall Sample Agreement: 107 out of 112 samples (96% agreement) showed the same result between the new device and the predicate devices (Varelisa ANA Profile and Varelisa dsDNA Antibodies Assay). Individual Parameter Agreement: 845 of 876 single determinations (96%) were in agreement between the new device and the predicate devices. Reference Sera Agreement: A total agreement was observed when comparing results for ANA Reference Sera CDC-1 to CDC-10; all 10 sera showed correct specificities with both the new and predicate devices.
	Agreement Table (n=876 determinations):

Acceptance Criteria (Implicit)

Reported Device Performance

High degree of correlation between new device and predicate devices.

Overall Sample Agreement: 107 out of 112 samples (96% agreement) showed the same result between the new device and the predicate devices (Varelisa ANA Profile and Varelisa dsDNA Antibodies Assay). Individual Parameter Agreement: 845 of 876 single determinations (96%) were in agreement between the new device and the predicate devices. Reference Sera Agreement: A total agreement was observed when comparing results for ANA Reference Sera CDC-1 to CDC-10; all 10 sera showed correct specificities with both the new and predicate devices.

Agreement Table (n=876 determinations):

2. Sample Size and Data Provenance for the Test Set

Sample Size for Test Set: 112 samples were used, including 20 apparently healthy blood donors.
Data Provenance: Not explicitly stated (e.g., country of origin). The study is retrospective in the sense that existing samples (including "apparently healthy blood donors") were tested using both devices.

3. Number of Experts and Qualifications for Ground Truth

This information is not provided in the given text. The ground truth for the comparison is the results obtained from the predicate devices, not an independent expert consensus on patient status.

4. Adjudication Method for the Test Set

This information is not applicable as the comparison is directly between the results of the new device and the predicate devices. There's no mention of a human adjudication process for discrepancies.

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

No, an MRMC comparative effectiveness study was not done. This study focuses on the performance of a diagnostic kit (an in-vitro diagnostic device) compared to predicate devices, not on the impact of a device on human readers' interpretive performance.

6. Standalone Performance Study

Yes, a standalone study was done, in the sense that the Varelisa ReCombi ANA Profile was tested independently on the 112 samples and its results were then compared to those of the predicate devices. The performance metrics of 96% agreement (overall and individual parameter) are indicative of its standalone performance in relation to the predicate.

7. Type of Ground Truth Used

The "ground truth" for this study was the results obtained from the predicate devices (Varelisa ANA Profile and Varelisa dsDNA Antibodies Assay). Additionally, the study used ANA Reference Sera CDC-1 to CDC-10 from the Centers of Disease Control and Prevention for which the "correct specificities" served as another form of ground truth.

8. Sample Size for the Training Set

This information is not provided as this is an in-vitro diagnostic device and the "training set" concept (as usually applied to AI/machine learning) is not directly relevant here. The device's formulation and manufacturing would be based on internal development and validation, but not a "training set" in the computational sense.

9. How Ground Truth for Training Set Was Established

This information is not applicable as there is no mention of a training set in the AI/machine learning context. The development of the Varelisa ReCombi ANA Profile would have involved rigorous R&D and internal validation to ensure its reagents and methodology accurately detect the target antibodies, but this isn't described in terms of a "training set" and "ground truth" as typically understood in AI studies.

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.

Assigned 510(k) Number:	K993109
Date of Summary Preparation:	September 7, 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® ReCombi ANA Profile
Common Name:	Antinuclear antibody immunological test
Classification:

Product Name	Product Code	Class	CFR
Varelisa® ReCombi ANA Profile	82LJM	II	866.5100

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Substantial Equivalence to:

Varelisa® ANA Profile and Varelisa® dsDNA Antibodies Assays

Intended Use Statement:

General Description of the Device

The Varelisa ReCombi ANA Profile is an enzyme immunoassay for the individual qualitative determination of 8 antinuclear antibodies in serum or plasma.

The determination of antinuclear antibodies (ANA) is of central importance for the clinical diagnosis of rheumatic diseases. The presence of ANA suggests the possibility of rheumatic autoimmune diseases. These diseases include Systemic Lupus Erythematosus, Polymyositis/ Dermatomyositis, Scleroderma, Sjögren's Syndrome and Mixed Connective Tissue Diseases.

Device Comparison:

A correlation study was performed comparing the new device, Varelisa ReCombi ANA Profile Assay, to the predicate devices, Varelisa ANA Profile and Varelisa dsDNA Antibodies Assay. 112 samples, including 20 apparently healthy blood donors were assayed using both tests.

A high degree of correlation is demonstrated in the correlation study. 107 out of 112 samples were found with the same result (96% agreement). Considering the individual parameters, 845 of 876 single determinations (96%) were in agreement between the new device and the predicate devices.

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In addition a total agreement is observed when comparing the results obtained for the ANA Reference Sera CDC-1 to CDC-10 from the Centers of Disease Control and Prevention. With both thenew device and predicate devices, all 10 sera were found with the correct specificities.

These data clearly demonstrate that the new device, Varelisa® ReCombi ANA Profile is substantially equivalent to the predicate devices, Varelisa ANA Profile and Varelisa dsDNA Antibodies.

	n = 876determinations	Varelisa ANA Profile and Varelisa dsDNA Abs. Assay
		positive	equivocal	negative
VARELISAReCombiANA Profile	positive	120	7	4
	equivocal	5	8	5
	negative	2	8	717

The new device Varelisa® ReCombi ANA Screen shows an excellent correlation with the predicate devices, Varelisa ANA Profile and Varelisa dsDNA Antibodies.

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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 circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with three lines representing its wings.

Nov 1 2 1999

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Karen E. Matis Manager, Regulatory Affairs and Quality Management Diagnostics Division, US Operations Pharmacia & Upjohn 7000 Portage Road 7425-248-01 Kalamazoo, Michigan 49001-0199

Re: K993109 Trade Name: Varelisa ReCombi ANA Profile Regulatory Class: II Product Code: LJM Dated: September 16, 1999 Received: September 17, 1999

Dear Ms. Matis:

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 (OS) 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 (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/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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Varelisa® ReCombi ANA Profile 510(k) Submission Section 1. Indications For Use Statement

510(k) Number: K993109

Device Name: Varelisa ReCombi ANA Profile

Peter E. Maxim

(Division Sign-Off)
Division of Clinical Laboratory Devices K993109
510(k) Number

(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

00 00001

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).