The Varelisa Histone Antibodies EIA kit is designed for the semiquantitative and qualitative determination of IgG and IgM antibodies to histone in serum or plasma to aid in the diagnosis of systemic lupus erythematosus (SLE) or druginduced lupus erythematosus (DIL).

Device Description

Varelisa Histone Antibodies is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of histone antibodies in human serum or plasma. The wells of a microtiterplate are coated with human histone antigen. Antibodies specific for histones 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.

AI/ML Overview

This submission is for an in-vitro diagnostic device, not an AI/ML powered device. Hence the provided sections of the 510k summary do not include specific "acceptance criteria" based on performance metrics like sensitivity, specificity, or AUC, nor do they detail a study designed to "prove" the device meets such criteria in the way one might expect for an AI/ML algorithm.

Instead, the submission focuses on demonstrating substantial equivalence to a previously legally marketed predicate device (INOVA QUANTA Lite™ Histone IgG). The "acceptance criteria" are implied by the demonstration of comparable performance and alignment with the predicate device regarding its intended use for aiding in the diagnosis of SLE or DIL.

Here's an interpretation based on the provided text, framed to address your requested points where applicable, and noting where information is not available due to the nature of the device:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is an in-vitro diagnostic (assay) device, the "acceptance criteria" are not explicitly stated as numerical performance targets (e.g., "sensitivity must be >90%"). Instead, they are interpreted as demonstrating comparable performance to the predicate device and expected results from medical literature. The "reported device performance" is qualitative and refers to the overall comparability.

Acceptance Criteria (Implied)	Reported Device Performance
Substantial Equivalence to Predicate Device: The device should perform comparably to the INOVA QUANTA Lite™ Histone IgG assay.	Laboratory equivalence supported by: - Results from 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.
Accordance with Medical Literature: Performance should align with established medical understanding of histone antibodies in SLE/DIL diagnosis.	The data show that the assay performs as expected from the medical literature.
Intended Use Fulfilled: Designed for semiquantitative and qualitative determination of IgG and IgM antibodies to histone.	The device is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of histone antibodies in human serum or plasma. It detects Anti-Histone IgG and IgM antibodies.
Methodological Comparability: Indirect noncompetitive enzyme immunoassay, similar sample dilutions, comparable antigens, and detection systems.	Both assays are indirect noncompetitive enzyme immunoassays for the semiquantitative determination of antibodies against Histone in serum. Both recommend the same sample dilutions and use comparable antigens and detection systems. (Note: Varelisa detects IgG and IgM, predicate detects only IgG).

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

Sample Size: Not explicitly stated. The text mentions "a comparison study analyzing positive, equivocal and negative sera" and "samples from apparently healthy subjects (normal population)," but no specific numbers are given for these cohorts.
Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective).

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

This information is not applicable and hence not provided for an in-vitro diagnostic assay comparison study. "Ground truth" for these types of tests typically refers to well-characterized patient samples with known clinical diagnoses or reference method results, rather than expert consensus on image interpretation.

4. Adjudication Method for the Test Set

Not applicable and not provided for this type of device.

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

Not applicable. This is an in-vitro diagnostic assay, not an AI-assisted diagnostic tool that would involve human readers interpreting output.

6. Standalone Performance Study (Algorithm Only)

Not applicable. This is an assay kit; its performance is its standalone performance when used in a laboratory setting. There isn't an "algorithm" in the typical sense of AI/ML. The "device performance" described in point 1 serves as its standalone performance.

7. Type of Ground Truth Used

The "ground truth" implicitly used for this type of comparison would be clinical diagnosis (e.g., patients diagnosed with SLE/DIL vs. healthy controls) and/or reference laboratory methods/externally defined calibrators for the detection of histone antibodies, against which the assay results are correlated. The text mentions "positive, equivocal and negative sera" and "samples from apparently healthy subjects (normal population)," implying clinically characterized samples.

8. Sample Size for the Training Set

Not applicable. This is an immunoassay kit whose reagents and protocol are developed based on scientific principles of antigen-antibody binding, not through a "training set" in the context of machine learning.

9. How Ground Truth for the Training Set Was Established

Not applicable for the reasons mentioned in point 8.

Summary

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510(K) SUMMARY OF SAFETY AND MAY 1 4 2004 9. EFFECTIVENESS

This summary of safety and effectiveness information is being submitted in Fills ballinary of or execuirements of The Safety Medical Devices Act of 1990 (SMDA 1990) and 21 CFR Part 807.92.

Assigned 510(k) Number:	K040810
Date of Summary Preparation:	March, 17 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® Histone Antibodies
Common Name:	Histone antinuclear autoantibodyimmunological test system

Classification

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

Substantial Equivalence to

INOVA QUANTA Lite™ Histone

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Intended Use Statement

General Description of the Device

Varelisa Histone Antibodies is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of histone antibodies in human serum or plasma. Antibodies specific for histones present in the patient sample bind to the antigen.

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

Varelisa® Histone Antibodies Test Principle

Device Comparison

Both assays (the predicate and the new device) are indirect noncompetitive enzyme immunoassays for the semiquantitative determination of antibodies against Histone in serum. Both assays recommend the same sample dilutions and use comparable antigens and detection systems.

In accordance to the relevant scientific literature both assays state in the Intended Use, that the measuring of the antibodies against histone provides aid in the diagnosis of systemic lupus erythematosus (SLE) or drug-induced lupus erythematosus (DIL).

A difference between both assays is that the INOVA QUANTA Lite™ Histone IgG is only recommended for use in serum specimen while the PHARMACIA Varelisa Histone Antibodies is, besides a limitation given for the use of plasma preparations with heparin, intended for use with serum and plasma.

The Varelisa Histone Antibodies is directed against Anti-Histone IgG and IgM antibodies while the predicate device detects Anti-Histone IgG antibodies only.

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The cut-off in the INOVA QUANTA Lite™ Histone IgG assay is evaluated by using a low and a high positive Standard and a grading of the results in negative, weak, moderate and strong positive. PHARMACIA Varelisa Histone Antibodies assay uses a set of six Calibrators and classifies the results as negative, equivocal and positive.

Laboratory equivalence

The comparability of INOVA QUANTA Lite™ Histone IgG and Varelisa Histone IgM/IgG 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.

In summary, all available data support that the new device, PHARMACIA Varelisa Histone IgM/IgG Antibodies Assay is substantially equivalent to the predicate device. INOVA QUANTA Lite™ Histone IgG 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 consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling three stylized human profiles facing to the right, with flowing lines suggesting movement or progress.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 1 4 2004

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

K040810 Trade/Device Name: Varelisa® Histone Antibodies Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LJM Dated: March 19, 2004 Received: March 29, 2004

Dear Dr. Linss:

Re:

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 Fedcral 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).

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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,

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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510(k) Number: _______________________________________________________________________________________________________________________________________________________________

Device Name: Varelisa® Histone Antibodies

Intended Use Statement

The Varelisa Histone Antibodies EIA kit is designed for the semiquantitative and qualitative determination of IgG and IgM antibodies to histome in serum or plasma to lugus qualifative determination of Igo and Igni and Outs (SLE) or drug-induced lupus erythematosus (DIL).

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Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use	✓	OR	Over-The-Counter Use
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(Per 21 CFR 801.109)
Division Sign-Off	Mara Chan

Office of In Vitro Diagnostic Device Evaluation and Safety

K040810

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).