The Varelisa Cardiolipin IgA Antibodies EIA kit is designed for the semiquantitative and qualitative determination of IgA 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 IgA Antibodies is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of IgA 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

The provided text describes a 510(k) submission for a modified medical device, the Varelisa® Cardiolipin IgA Antibodies assay. The submission primarily focuses on demonstrating substantial equivalence to a predicate device rather than detailing specific acceptance criteria and a standalone study proving its performance against those criteria.

However, based on the information provided, we can infer some aspects related to the study conducted for comparison.

Here's an analysis of the provided information:

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

The document does not explicitly state numerical acceptance criteria (e.g., specific sensitivity, specificity, accuracy thresholds). The primary "acceptance criteria" for a 510(k) submission, as implied, is demonstrating substantial equivalence to a predicate device.

The reported device performance is described qualitatively in the "Laboratory equivalence" section:

Acceptance Criteria (Inferred from Substantial Equivalence)	Reported Device Performance
Comparability with predicate device (Varelisa® Cardiolipin (IgA) Antibodies)	Data from a comparison study analyzing positive, equivocal, and negative sera, externally defined Calibrators, and samples from apparently healthy subjects show comparability.
Assay performs as expected from medical literature	"The data show that the assay performs as expected from the medical literature."
Substantial equivalence to predicate device	"all available data support that the new/modified device... is substantially equivalent to the predicate/original device..."

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

Sample Size for Test Set: Not explicitly stated. The document mentions "positive, equivocal and negative sera," "externally defined Calibrators," and "samples from apparently healthy subjects (normal population)," but no specific numbers.
Data Provenance: Not explicitly stated. It's likely the study was conducted in Germany, given the manufacturer's location (Pharmacia Deutschland GmbH) and the company contact person's address. The type of study (retrospective or prospective) is also not specified.

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)

Not applicable. The ground truth for this type of in vitro diagnostic device (immunological test) is typically established by the results of the predicate device, known positive/negative samples, or established clinical definitions of the condition, rather than expert interpretation of images or clinical cases. There's no mention of experts establishing ground truth in the context of radiologists or similar roles.

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

Not applicable. This concept is relevant for studies where human interpretation or consensus is required to establish ground truth or classify cases. For an immunoassay, the results are quantitative or semi-quantitative and typically don't require adjudication between human readers.

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

Not applicable. This device is an in vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic tool that aids human readers. Therefore, an MRMC study and analysis of human reader improvement with AI assistance are not relevant.

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

Yes, implicitly. The "comparison study" and "laboratory equivalence" assessment described refer to the performance of the device itself (the assay) as a standalone diagnostic tool. The purpose is to show that the modified assay yields comparable results to the predicate assay.

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

The ground truth appears to be established by:

Reference to the predicate device (Varelisa® Cardiolipin (IgA) Antibodies) through comparison studies with positive, equivocal, and negative sera.
Externally defined Calibrators, which are reference materials with known concentrations.
Samples from apparently healthy subjects, which serve as negative controls.
The overall understanding of the medical literature regarding anti-cardiolipin antibodies in the context of APS and SLE.

8. The sample size for the training set

Not applicable in the conventional sense of machine learning. This is an immunoassay, not a machine learning algorithm that requires a "training set." The assay itself is a chemical and biological measurement system.

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

Not applicable, as it's not a machine learning model with a training set. The assay's "calibration" would involve using known standards and calibrators, as mentioned, but these are part of the assay's operational parameters rather than a "training set" for an algorithm.

Summary

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MAY 0 2 2002

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: K020 757 Date of Summary Preparation: February 15, 2002 Distributor: Pharmacia Diagnostics Division, US Operation 7425-248-1 7000 Portage Road Kalamazoo, MI 49001 Manufacturer: Pharmacia Deutschland GmbH, Diagnostics Division Munzingerstrasse 7 D-79111 Freiburg, Germany 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 IgA Antibodies Common Name: Cardiolipin autoantibody immunological test system Classification: Product Name Product Code Class CFR

82MID

Varelisa® Cardiolipin IgA Antibodies

866.5560

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Substantial Equivalence to:

Varelisa® Cardiolipin (IgA) 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 increased incidence of venous/arterial thromboses (including apoplexy), an 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 plays a direct role in the pathogenesis of APS.

Varelisa® Cardiolipin IgA Antibodies Test Principle

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

Laboratory equivalence

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

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

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Image /page/3/Picture/0 description: The image is a black and white seal for the Department of Health & Human Services. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES U.S.A." arranged around the perimeter. In the center of the seal is a stylized image of a bird-like figure, possibly representing an eagle or other national symbol.

DEPARTMENT OF HEALTH & HUMAN SERVICES

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: K020757

Trade/Device Name: Varelisa® Cardiolipin IgA 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 notification. The FDA finding of substantial 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 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 Butman

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

Kozo 157 510(k) Number: ___

Device Name: Varelisa® Cardiolipin IgA Antibodies

Intended Use Statement

The Varelisa Cardiolipin IgA Antibodies ELA kit is designed for the semiquantitative and qualitative determination of IgA 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).

(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)

Satha Menon

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K020757

CL-Al.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).