The Varelisa Cardiolipin Antibodies Screen EIA kit is designed for the qualitative determination of antibodies against cardiolivin 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 Antibodies Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of antibodies against cardiolipin in serum or plasma.

AI/ML Overview

Here's the information about the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. A table of acceptance criteria and the reported device performance

The provided 510(k) summary does not explicitly state numerical acceptance criteria in the typical sense (e.g., minimum sensitivity, specificity, or accuracy percentages). Instead, the study focuses on demonstrating substantial equivalence to a predicate device and showing the assay "performs as expected from the medical literature."

The "reported device performance" is described in terms of its comparability to the original/predicate device.

Acceptance Criteria (Implied)	Reported (New Device) Performance
Substantial equivalence to predicate device	Data supports substantial equivalence to the predicate/original device.
Performs as expected from medical literature	Data shows the assay performs as expected from the medical literature.
Comparability across positive, equivocal, and negative sera	Results obtained within a comparison study analyzing positive, equivocal, and negative sera. (No specific numerical results provided, but the study implies they were comparable enough to support equivalence).
Comparability with externally defined Calibrators	Results obtained for externally defined Calibrators. (No specific numerical results provided, but the study implies they were comparable enough to support equivalence).
Performance with samples from apparently healthy subjects (normal population)	Results obtained for samples from apparently healthy subjects (normal population). (No specific numerical results provided, but the study implies they were comparable enough to support equivalence).
Intended Use reflects current scientific knowledge	The intended use was adapted to the current state of scientific knowledge, reflecting the diagnostic relevance of anti-cardiolipin antibodies in antiphospholipid syndrome (APS) and thrombotic risk in SLE. (This is a design criterion rather than a performance metric, but it is a key aspect of the "new" device's justification).

2. Sample sizes used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

The text does not provide specific sample sizes for the "test set." It mentions data from:

"a comparison study analyzing positive, equivocal and negative sera."
"externally defined Calibrators."
"samples from apparently healthy subjects (normal population)."

The provenance of the data (country of origin, retrospective/prospective) is not explicitly stated. The manufacturer is based in Germany, so it's plausible the data originated from there or other European countries, but this is not confirmed.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)

This information is not provided in the document. The text does not describe how ground truth was established for the comparison studies.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

This information is not provided in the document.

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

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic tool that would typically involve human readers interpreting images or data. The study focuses on the analytical performance of the assay itself compared to a previous version.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, in a sense, a "standalone" performance evaluation was done as this is an IVD device. The study evaluates the performance of the modified Varelisa® Cardiolipin Antibodies Screen assay as a standalone diagnostic tool, comparing it to its predicate version and its expected performance based on medical literature. Human intervention (other than laboratory procedures) in the interpretation of the assay result for diagnosis is inherent in the clinical use of such tests, but the submitted study evaluated the device's technical performance directly.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The document does not explicitly state the "ground truth" used for the comparison study. Given that it's a diagnostic test for antibodies, the ground truth would typically be established through:

Clinical diagnosis of APS/SLE: For the "positive" and "negative" sera, this would likely involve a clinical diagnosis by physicians based on established criteria and other laboratory findings, or
Reference laboratory methods: Comparison against a gold-standard or highly validated reference method for cardiolipin antibodies.
Expert consensus: In some cases, expert panels might classify samples.

The text mentions "externally defined Calibrators," which would have their values established by a reference method.

8. The sample size for the training set

This information is not provided. Since this is an immunoassay and not a machine learning model, there isn't a "training set" in the typical AI/ML sense. The development of the assay, including optimizing the antigen supplier and blocking procedure, would have involved internal validation and optimization studies, but these are not described as a "training set" with specific sample sizes.

9. How the ground truth for the training set was established

As there is no "training set" in the AI/ML context, this question is not applicable. For the development and optimization of the immunoassay, the "ground truth" would have come from established concentrations of analytes, known positive/negative samples, and comparison to existing validated methods during the assay development process. However, the details of these are not provided.

Summary

{0}------------------------------------------------

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:	K023433
Date of Summary Preparation:	September 30, 2002
Distributor:	PharmaciaDiagnostics Division, US Operation7425-248-17000 Portage RoadKalamazoo, MI 49001
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® Cardiolipin Antibodies Screen
Common Name:	Cardiolipin autoantibody immunological testsystem

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

{1}------------------------------------------------

Substantial Equivalence to:

Varelisa® Cardiolipin Antibodies Screen

Intended Use Statement

General Description of the Device

The Varelisa Cardiolipin Antibodies Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of antibodies against cardiolipin in serum or plasma.

Anti-cardiolipin antibodies (ACA) belong to the group of anti-phospholipid antibodies (aPL). ACA 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 ACA/LA-positive patients. Elevated levels of ACA may also be found in patients with cerebrovascular insufficiency or myocardial infarction, aPL plays a direct role in the pathogenesis of APS.

Varelisa® Cardiolipin Antibodies Screen Test Principle

Varelisa Cardiolipin Antibodies Screen is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of cardiolipin 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 antigenantibody 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.

{2}------------------------------------------------

Device Comparison

Varelisa Cardiolipin Antibodies Screen (the original/predicate device) and Varelisa Cardiolipin Antibodies Screen (the new/modified device) both are indirect noncompetitive enzyme immunoassays for qualitative determination of 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 Antibodies Screen 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 B2glycoprotein I in the blocking buffer.

Laboratory equivalence

The comparability of the new and the old version Varelisa Cardiolipin Antibodies Screen 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. Differing results are probably due to the changed blocking procedure.

In summary, all available data support that the new/modified device, Varelisa Cardiolipin Antibodies Screen Assay is substantially equivalent to the predicate/original device, Varelisa Cardiolipin Antibodies Screen Assay, and that the new/modified device performs according to state-of-the-art expectations.

{3}------------------------------------------------

DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/1 description: The image shows the seal for the Department of Health & Human Services USA. The seal is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. In the center of the seal is an abstract symbol that resembles three stylized human profiles.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 1 3 2002

Mr. Michael Linss Manager, Regulatory Affairs Pharmacia Deutschland GmbH Diagnostics Division Munzinger Strasse 7 D-79111 Freiburg, Germany

Re: K023433

Trade/Device Name: Varelisa® Cardiolipin Antibodies Screen Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple Autoantibodies Immunological Test System Regulatory Class: Class II Product Code: MID Dated: October 11, 2002 Received: October 15, 2002

Dear Mr. 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. Iisting 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 (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

{4}------------------------------------------------

Page 2 -

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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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,

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

{5}------------------------------------------------

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

510(k) Number:

Koas 433

Device Name: Varelisa® Cardiolipin Antibodies Screen

Intended Use Statement

The Varelisa Cardiolipin Antibodies Screen EIA kit is designed for the qualitative determination of cardiolipin antibodies 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).

(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)

Signature

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number	C023933

CLS1.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).