The Varelisa Cardiolipin IgG Antibodies EIA kit is designed for the semiquantitative and qualitative determination of IgG antibodies against cardiolipin in serum or plasma to aid in the diagnosis of antiphospholipid syndrome (APS) and to evaluate the thrombotic risk in patients with systemic lupus erythematosus (SLE).

Device Description

The Varelisa Cardiolipin IgG Antibodies is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of IgG antibodies against cardiolipin in human serum or plasma. The wells of a microplate are coated with bovine cardiolipin antigen. Antibodies specific for cardiolipin present in the patient sample bind to the 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 a breakdown of the acceptance criteria and study information for the Varelisa® Cardiolipin IgG Antibodies device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text does not explicitly state specific numerical acceptance criteria for the device. Instead, it focuses on demonstrating "laboratory equivalence" and "substantial equivalence" to a predicate device. The performance is summarized qualitatively.

Acceptance Criteria Category	Reported Device Performance	Comments
Laboratory Equivalence	The new device performs as expected from medical literature. Comparisons showed that results obtained within a comparison study analyzing positive, equivocal, and negative sera, as well as results for externally defined Calibrators and Quality Assessment sera, and samples from apparently healthy subjects, supported comparability. Minor differing results noted were probably due to a changed blocking procedure, but the overall conclusion was substantial equivalence.	The criteria are implicitly met by demonstrating that the new device's performance aligns with the predicate and scientific understanding. Specific quantitative targets for agreement (e.g., % positive agreement, % negative agreement) are not provided.
Intended Use	The device is designed for semiquantitative and qualitative determination of IgG antibodies against cardiolipin in serum or plasma to aid in the diagnosis of antiphospholipid syndrome (APS) and to evaluate the thrombotic risk in patients with systemic lupus erythematosus (SLE).	The intended use statement itself serves as a high-level criterion, and the study aims to show the device fulfills this use.
Substantial Equivalence	All available data support that the new/modified device is substantially equivalent to the predicate/original device, and performs according to state-of-the-art expectations.	This is the overarching "acceptance criterion" for 510(k) clearance in this context.

2. Sample Sizes and Data Provenance for the Test Set

Sample Size: The document mentions "positive, equivocal and negative sera," "externally defined Calibrators and Quality Assessment sera," and "samples from apparently healthy subjects (normal population)." However, the specific number of samples in each category tested for the comparison study is not provided.
Data Provenance: Not explicitly stated. Given the manufacturer (Pharmacia Deutschland GmbH) is in Germany, it is reasonable to infer that some data might be from Europe, but this is not confirmed. The document does not specify whether the data was retrospective or prospective.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of experts to establish ground truth for the test set. The nature of the comparison (comparing to a predicate device and "externally defined Calibrators and Quality Assessment sera") suggests that the "ground truth" for the test set was likely derived from the established values of these calibrators and known statuses of the clinical samples (positive, negative, equivocal) as determined by the predicate device or other reference methods.

4. Adjudication Method

Not applicable/Not mentioned. There is no indication of an adjudication method used, as expert consensus for ground truth determination is not described.

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

No, an MRMC comparative effectiveness study was not done. This document describes the validation of an in vitro diagnostic (IVD) test kit, which typically does not involve human readers interpreting results in the same way an imaging or pathology AI system would. The "reading" is done by the instrument quantifying antibody levels.

6. Standalone (Algorithm Only) Performance Study

Yes, this is essentially a standalone performance assessment. The device (an EIA kit) operates without a human-in-the-loop interpreting the primary output. Its performance is evaluated based on its ability to detect and quantify antibodies in samples.

7. Type of Ground Truth Used

The ground truth appears to be based on:
- Comparison to a Predicate Device: The performance of the new device was compared against the Varelisa® Cardiolipin (IgG) Antibodies (the original/predicate device).
- Externally Defined Calibrators and Quality Assessment Sera: These materials would have established, reference values for the analytes.
- Known Clinical Status: Samples were categorized as "positive, equivocal and negative sera," implying that their actual status for cardiolipin antibodies was known through other means (likely the predicate or reference methods).
It does not explicitly state "pathology," "expert consensus," or "outcomes data" as the primary form of ground truth for analytical performance, though the clinical relevance (APS diagnosis, thrombotic risk) implies underlying clinical outcomes would have defined the initial understanding of cardiolipin antibodies.

8. Sample Size for the Training Set

The document does not discuss a separate "training set" in the context of an AI/algorithm. This is an immunoassay kit, not a machine learning model that typically requires a distinct training phase. The " Comparability of the new and the old version" section describes the studies used to demonstrate equivalency.

9. How Ground Truth for the Training Set Was Established

Not applicable. As this is an immunoassay kit, rather than an AI algorithm requiring a training set, the concept of establishing ground truth for a training set does not apply in the conventional sense. The "training" for such a device is in its biochemical design and optimization during development, validated against known standards and clinical samples.

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: K020752

Date of Summary Preparation:

February 11, 2002

Munzingerstrasse 7

D-79111 Freiburg, Germany

Distributor:

Pharmacia Diagnostics Division, US Operation 7425-248-1 7000 Portage Road Kalamazoo, MI 49001

Pharmacia Deutschland GmbH, Diagnostics Division

Manufacturer:

Company Contact Person:

Michael Linss Manager, Regulatory Affairs Pharmacia Deutschland GmbH Diagnostics Division Munzingerstrasse 7 Freiburg, Germany Telephone +49-761-47-805-310 Facsimile +49-761-47-805-120

Device Name:

Varelisa® Cardiolipin IgG Antibodies

Common Name:

Cardiolipin autoantibody immunological test system

Classification:

Product Name	Product Code	Class	CFR
Varelisa® Cardiolipin IgG Antibodies	82MID	II	866.5560

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Substantial Equivalence to:

Varelisa® Cardiolipin (IgG) Antibodies

Intended Use Statement

General Description of the Device

Anti-cardiolipin antibodies (aCL) belong to the group of anti-phospholipid antibodies (aPL). aCL are considered to be of significant diagnostic relevance, as a correlation has been found between these antibodies and a tendency towards thromboses. This results in an increased incidence of venous/arterial thromboses (including apoplexy), thrombocytopenia, livedo reticularis, habitual abortion and neurological manifestations in aCL/LA-positive patients. Elevated levels of aCL may also be found in patients with cerebrovascular insufficiency or myocardial infarction. aPL play a direct role in the pathogenesis of APS.

Varelisa® Cardiolipin IgG Antibodies Test Principle

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

Varelisa Cardiolipin (IgG) Antibodies (the original/predicate device) and Varelisa Cardiolipin IgG Antibodies (the new/modified device) both are indirect noncompetitive enzyme immunoassays for semiquantitative and qualitative determination of IgG antibodies against Cardiolipin in serum or plasma.

Based on currently available data from the literature the measuring of these antibodies not only provides aid in the evaluation of the thrombotic risk in patients with systemic lupus erythematosus, but also aids in the diagnosis of the antiphospholipid syndrome (APS). Thus the intended use of Varelisa Cardiolipin IgG Antibodies was adapted to the current state of scientific knowledge.

The essential differences between both assays are the new choice of antigen supplier and a changed blocking procedure.

Important common features between old and new version are the nature of the antigen determining the specificity of the assay, Bovine Cardiolipin, and the presence of $2glycoprotein I in the blocking buffer.

Laboratory equivalence

The comparability of the new and the old version Varelisa Cardiolipin 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 and Quality Assessment sera
results obtained for samples from apparently healthy subjects (normal population) .

The data show that the assay performs as expected from the medical literature. Differing results are probably due to the changed blocking procedure.

In summary, all available data support that the new/modified device, Varelisa Cardiolipin IgG Antibodies Assay is substantially equivalent to the predicate/original device, Varelisa Cardiolipin (IgG) Antibodies Assay, and that the new/modified device performs according to state-of-the-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 the department's name arranged in a circular fashion around a symbol. The symbol is a stylized representation of a human figure, with three overlapping profiles suggesting a sense of community and support. The logo is presented in black and white.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Michael Linss, Ph.D. Manager, Regulatory Affairs Pharmacia Deutschland GmbH Diagnostics Division Munzinger Strasse 7 Freiburg GERMANY

MAY 0 2 2002

Re: K020752

Trade/Device Name: Varelisa® Cardiolipin IgG Antibodies Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple Autoantibodies Immunological Test Sytem Regulatory Class: II Product Code: MID Dated: March 6, 2002 Received: March 7, 2002

Dear Dr. 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2

This letter will allow you to begin marketing your device as described in your 510(k) premarket This letter will and in you disubstantial equivalence of your device to a legally marketed nouticate 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 If you desire specific dain vitro diagnostic devices), please contact the Office of Compliance at additionally 607.10 101 ====================================================================================================================================================== (301) 594-1566. entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small monitation on your respond 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,

Steven Putman

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® Cardiolipin IgG Antibodies- Device Modification 510(k) Submission Section 1. Indications for Use Statement

Kogo752 510(k) Number:

Device Name: Varelisa® Cardiolipin IgG Antibodies

Intended Use Statement

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use v

Over-The-Counter Use

(Per 21 CFR 801.109)

Dorothea Menon

(Division Sign-Off Division of Clinical Lat 510(k) Number

CL-G1.doc

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).