The Varelisa ssDNA Antibodies EIA kit is designed for the semiquantitative and qualitative determination of anti-single stranded DNA (ssDNA) autoantibodies in serum or plasma. In conjunction with the Varelisa dsDNA Antibodies kit it assists in the diagnosis of systemic lupus erythematosus (SLE) and certain other rheumatic diseases. The test is not definitive in isolation but has to be seen as one parameter in a multicriterion diagnostic process.

Device Description

Varelisa ssDNA Antibodies is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of ssDNA antibodies in human serum or plasma. Antibodies specific for ssDNA present in the patient sample bind to the antigen. The assay should be used in combination with the Varelisa dsDNA Antibodies.

The test kit contains microplate strips coated with synthetic ssDNA, calibrators, positive and negative controls, enzyme-labeled conjugate, substrate and substrate stop solution, Sample Diluent and wash buffer.

AI/ML Overview

This document describes the Varelisa® ssDNA Antibodies, an indirect noncompetitive enzyme immunoassay for the semi-quantitative and qualitative determination of anti-single stranded DNA (ssDNA) autoantibodies in human serum or plasma. It is intended to assist in the diagnosis of systemic lupus erythematosus (SLE) and other rheumatic diseases, to be used in conjunction with a dsDNA antibodies kit.

1. Table of Acceptance Criteria and Reported Device Performance
The submission document states that "all available data support that the new device, PHARMACIA Varelisa ssDNA Antibodies Assay is substantially equivalent to the predicate device, INOVA QUANTA Lite™ ssDNA Assay, and that the new device performs according to state-of-the-art expectations." However, specific numerical acceptance criteria for performance metrics (such as sensitivity, specificity, accuracy) and their corresponding reported device performance values are not explicitly provided in the given text.

The data provided primarily focuses on demonstrating "comparability" and "substantial equivalence" to the predicate device rather than defining and meeting specific quantitative acceptance criteria. The text mentions "results obtained within a comparison study analyzing positive, equivocal and negative sera" and "results obtained for samples from apparently healthy subjects (normal population)" to support comparability.

Acceptance Criteria	Reported Device Performance
Not explicitly defined in numerical terms (e.g., sensitivity > X%, specificity > Y%)	Device performs "as expected from the medical literature" and is "suitable for serum and plasma samples." Confirmed to be "substantially equivalent" to the predicate device based on comparison studies across positive, equivocal, and negative sera, and healthy subjects.

2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the specific sample size used for the test set during the comparison study. It mentions a "data set including: results obtained within a comparison study analyzing positive, equivocal and negative sera" and "results obtained for samples from apparently healthy subjects (normal population)."

Sample Size for Test Set: Not explicitly stated.
Data Provenance: Not explicitly stated (e.g., country of origin). The study is described as a "comparison study" and involves "samples from apparently healthy subjects (normal population)," implying, but not confirming, a prospective collection for this specific study, or at least a retrospective analysis of collected samples for performance evaluation. It is not definitively stated if the data is retrospective or prospective.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not provide information on the number of experts used or their qualifications to establish the ground truth for the test set.

4. Adjudication Method for the Test Set
The document does not specify any adjudication method (e.g., 2+1, 3+1, none) used for the test set.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size with AI vs Without AI Assistance
This device is an in-vitro diagnostic (IVD) immunoassay kit, not an AI-powered diagnostic system involving human readers interpreting images or data with or without AI assistance. Therefore, a multi-reader multi-case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance is not applicable and was not performed.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
This refers to a standalone performance evaluation of the device itself (the immunoassay kit) in determining ssDNA antibodies. The document implies that the "comparison study analyzing positive, equivocal and negative sera" and "results obtained for samples from apparently healthy subjects" were indeed a standalone evaluation of the device against established classifications of these samples. The general principle of an immunoassay kit is to provide a result directly, so the performance described aligns with a "standalone" evaluation of the assay.

7. The Type of Ground Truth Used
The document states that the comparison study involved "positive, equivocal and negative sera" and "samples from apparently healthy subjects (normal population)." This indicates that the ground truth was based on:

Clinical Diagnosis/Classification: Samples were likely categorized as positive, equivocal, or negative for ssDNA antibodies, or as coming from "apparently healthy subjects," based on established clinical criteria, potentially including other diagnostic tests, clinical symptoms, and expert consensus.
External Calibrators: "Results obtained for externally defined Calibrators" were also used, suggesting the use of reference materials with known concentrations.

8. The Sample Size for the Training Set
The document does not explicitly mention a training set in the context of an AI/machine learning model. This device is an immunoassay kit for antibody detection, not a machine learning algorithm that requires a distinct training set. The "data set" mentioned seems to be for performance evaluation/comparison rather than training.

9. How the Ground Truth for the Training Set Was Established
As a training set for an AI/machine learning model is not applicable in this context, the method for establishing its ground truth is not mentioned.

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:	K040811
Date of Summary Preparation:	March 19, 2004
Manufacturer:	Pharmacia Deutschland GmbH,Diagnostics DivisionMunzinger Strasse 7D-79111 Freiburg, Germany
Company Contact Person:	Michael LinssManager, Regulatory AffairsPharmacia Deutschland GmbHDiagnostics DivisionMunzinger Strasse 7D-79111 Freiburg, Germany+49-761-47805-310(Phone)+49-761-47805-120 (Fax)
Device Name:	Varelisa® ssDNA Antibodies
Common Name:	ssDNA antinuclear antibodyimmunological test system

Classification

Product Name	Product Code	Class	CFR
Varelisa® ssDNA Antibodies	LJM	II	866.5100

Substantial Equivalence to

INOVA QUANTA Lite™ ssDNA

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Intended Use Statement

General Description of the Device

Varelisa® ssDNA Antibodies Test Principle

Varelisa ssDNA Antibodies is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of ssDNA antibodies in human serum or plasma. The wells of a microtiterplate are coated with synthetic ssDNA. Antibodies specific for ssDNA 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 semiquantitative and qualitative determination of IgG antibodies against ssDNA in serum. Both assays recommend the same sample dilutions and use comparable enzyme-linked conjugates and antigens. For evaluation of the assay both recommend to use a compatible dsDNA kit from the corresponding manufacturer and give comparable interpretations of the result. In accordance to the relevant scientific literature both assays state in the Intended Use, that the measuring of the antibodies against ssDNA provides aid in the diagnosis of SLE and other rheumatic diseases.

A difference between both assays is that the predicate device is only recommended for use in serum specimen while the new device is outlined for use with serum and plasma.

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Laboratory equivalence

The comparability of QUANTA Lite™ ssDNA and Varelisa ssDNA Antibodies 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. .
results obtained for samples from apparently healthy subjects (normal population).

The data show that the assay performs as expected from the medical literature. Furthermore the performance data show that the device is suitable for serum and plasma samples.

In summary, all available data support that the new device, PHARMACIA Varelisa ssDNA Antibodies Assay is substantially equivalent to the predicate device, INOVA QUANTA Lite™ ssDNA Assay, and that the new device performs according to state-of-the-art expectations.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized caduceus, which is a symbol of medicine and health. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the caduceus.

MAY 1 3 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Michael Linss, Ph.D. Manager, Compliance & Quality Pharmacia Deutschland GMBH Munzinger Strasse 7 Freiburg, Germany D 79111

K040811 Re: Trade/Device Name: Varelisa® ssDNA Antibodies Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LRM Dated: March 19, 2004 Received: March 29, 2004

Dear Dr. Linss:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your betermined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for aso stated in the encreativent of the enactment date of the Medical Device Amendments, or to conninered prior to may 20, 2011 accordance with the provisions of the Federal Food, Drug, de fices that hat o ocen require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The r ou may, dierelove, mains 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 your doviet to such additional controls. Existing major regulations affecting your device n may oc subject to back dades Federal Regulations (CFR), Parts 800 to 895. In addition, FDA ean or tound in fire announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean I lease be deviloed and itermination that your device complies with other requirements of the Act that + Drederal statutes and regulations administered by other Federal agencies. You must or any I vith 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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Page 2

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 I ou may 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. Arbolett

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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Varelisa® ssDNA Antibodies -- New Device 510(k) Submission Section 1. Indications for Use Statement

510(k) Number:

510(k) Number: _______________________________________________________________________________________________________________________________________________________________

Device Name: Varelisa® ssDNA Antibodies

Intended Use Statement

The Varelisa ssDNA Antibodies EIA kit is designed for the semiquantitative and qualitative determination of anti-single stranded DNA (ssDNA) autoantibodies in serum or plasma. In conjunction with the Varelisa dsDNA Antibodies kit it assists in Scrain of plasmic in conic lupus erythematosus (SLE) and certain other rheumatic diseases. The test is not definitive in isolation but has to be seen as one parameter in a multicriterion diagnostic process.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use	✓
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(Per 21 CFR 801.109)
OR

Over-The-Counter Use	__________
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	Maria Chan
	Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and SafetyKO40811 510(k)-

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).