The Varelisa ß2-Glycoprotein I IgM Antibodies EIA kit is designed for the semiquantitative and qualitative determination of ß2-glycoprotein I IgM antibodies in serum or plasma.

The presence of ß2-glycoprotein I antibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of thrombotic disorders related to the primary Antiphospholipid Syndrome or occurring secondary to systemic lupus erythematosus (SLE) or other autoimmune diseases.

Device Description

The Varelisa B2-Glycoprotein I IgM Antibodies Assay is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of B2-glycoprotein I IgM antibodies in serum or plasma.

The test kit contains microplate strips coated with human purified ß2glycoprotein I, calibrators, positive and negative controls, enzyme-labeled conjugate, substrate and substrate stop solution, buffered diluent and wash buffer.

AI/ML Overview

Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text does not explicitly state numerical acceptance criteria (e.g., sensitivity, specificity thresholds) for the Varelisa® B2-Glycoprotein I IgM Antibodies device. Instead, the study aims to demonstrate substantial equivalence to a predicate device, the INOVA QUANTA Lite™ ß2 GPI IgM. The reported performance is based on qualitative comparisons and the conclusion of substantial equivalence.

Acceptance Criteria (Implied)	Reported Device Performance
Comparability to predicate device (INOVA QUANTA Lite™ ß2 GPI IgM)	"The comparability of QUANTA LiteTM ß2 GPI IgM and Varelisa B2-Glycoprotein I IgM 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)."**
Effectiveness with serum samples	Implied to be effective as it's a common sample type for this assay type and compared to a predicate using serum.
Effectiveness with plasma samples	"Corresponding performance data underline the effectiveness of the assay with plasma as sample."
Performance as expected from medical literature	"The data show that the assay performs as expected from the medical literature."
Comparability of evaluation methods (OD-cutoff vs. decision point)	"Corresponding performance data show the comparability of the results."

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

Sample Size: The exact numerical sample size for the test set (comparison study analyzing positive, equivocal, and negative sera; externally defined calibrators; normal population) is not specified in the provided text.
Data Provenance: The text does not specify the country of origin of the data. It mentions "externally defined Calibrators" and "samples from apparently healthy subjects (normal population)". It is implied to be a retrospective study as it's a comparison study to a predicate.

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

This information is not provided in the text. The study focuses on demonstrating comparability between two assay kits, rather than establishing a gold standard diagnosis by human experts for the test set itself. The "ground truth" for the samples would have been their established status as positive, negative, or equivocal for the autoantibody.

4. Adjudication Method for the Test Set

This information is not provided in the text. Given it's a serological assay comparison, expert adjudication in the typical sense (e.g., for imaging interpretation) is unlikely to be the primary method for test set ground truth. The initial classification of samples (positive, negative, equivocal) would have been based on established laboratory methods or clinical diagnoses.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This type of study is more common for diagnostic imaging AI devices where human interpretation is a key component. The Varelisa® B2-Glycoprotein I IgM Antibodies device is an in-vitro diagnostic (IVD) assay kit for laboratory use, not an AI-powered diagnostic tool for human reader improvement.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, a standalone performance assessment was effectively done. The device itself is an in-vitro diagnostic assay that provides a result (semiquantitative or qualitative determination of antibodies) without direct human interpretation in the sense of an "algorithm only". The comparison study assesses the performance of this standalone assay against a predicate standalone assay. The results are based on the assay's output (e.g., optical density, antibody units), not on a human's interpretation of those results.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, Etc.)

The ground truth for the comparison study would likely have been established by:

Clinical Diagnosis / Established Patient Status: Samples categorized as "positive, equivocal, and negative sera" would have their status determined by established clinical diagnoses of thrombotic disorders, SLE, or other autoimmune diseases, in conjunction with other laboratory findings.
Reference Method Results: For the "externally defined Calibrators," their true value would be established by a reference method or traceable standard.
Healthy Population Screening: "Samples from apparently healthy subjects (normal population)" would be considered negative by definition for the condition.

The text does not explicitly state "pathology" or "outcomes data" as the direct ground truth, but clinical diagnosis often relies on these.

8. The Sample Size for the Training Set

This information is not applicable / not provided for this type of medical device submission. The Varelisa® B2-Glycoprotein I IgM Antibodies is a chemical reagent-based assay kit, not a machine learning or AI algorithm that requires a "training set" in the computational sense. The device's performance characteristics are established through analytical and clinical validation studies, not an algorithmic training process.

9. How the Ground Truth for the Training Set Was Established

This information is not applicable / not provided as there is no "training set" for this type of device.

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:	K040451
Date of Summary Preparation:	February 12, 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® B2-Glycoprotein I IgM Antibodies
Common Name:	ß2-Glycoprotein I autoantibodyimmunological test system
Classification

Product Name	Product Code	Class	CFR
Varelisa® β2-Glycoprotein IIgM Antibodies	MSV	II	866.5560

Substantial Equivalence to

INOVA QUANTA Lite™ ß2 GPI IgM

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Intended Use Statement

The Varelisa B2-Glycoprotein I IgM Antibodies EIA kit is designed for the semiquantitative and qualitative determination of B2-glycoprotein I IgM antibodies in serum or plasma.

The presence of B2-glycoprotein I antibodies can be used in conjunction with clinical findings and other laboratory tests to aid in the diagnosis of thrombotic disorders related to the primary Antiphospholipid Syndrome or occurring secondary to systemic lupus erythematosus (SLE) or other autoimmune diseases.

General Description of the Device

Varelisa® ß2-Glycoprotein I IgM Antibodies Test Principle

Varelisa B2-Glycoprotein I IgM Antibodies is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of B2-glycoprotein I IgM antibodies in human serum or plasma. The wells of a microplate are coated with human purified B2-glycoprotein I antigen. Antibodies specific for Bz-glycoprotein I 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

QUANTA LiteTM B2 GPI IgM (predicate device) and Varelisa B2-Glycoprotein I IgM Antibodies (new device) both are indirect noncompetitive enzyme immunoassays for semiquantitative and qualitative determination of IgM antibodies against ß2-Glycoprotein I in serum. Both assays recommend the same sample dilutions and use comparable antigens and enzyme-linked conjugates.

Based on currently available data from the literature the measuring of the antibodies against B2-glycoprotein I not only provides aid in the diagnosis of thrombotic disorders secondary to systemic lupus erythematosus or other autoimmune diseases, but also aids in the diagnosis of the primary

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antiphospholipid syndrome. Thus the intended use of Varelisa ß2-glycoprotein I Antibodies Screen was adapted to the current state of scientific knowledge. The corresponding literature is cited in the directions for use.

A difference between both assays is that the INOVA QUANTA Lite™ ß2 GPI IgM is only recommended for use in serum specimen while the PHARMACIA Varelisa B2-glycoprotein I IgM Antibodies is outlined for use with serum and plasma. Corresponding performance data underline the effectiveness of the assay with plasma as sample. Minor differences between both assays are restricted to contents of buffers and stop solution. The INOVA QUANTA Lite™ B2 GPI IgM assay is evaluated by using the decision point method. PHARMACIA Varelisa B2-glycoprotein I IgM Antibodies assay uses an ODcutoff for evaluation. Corresponding performance data show the comparability of the results.

Laboratory equivalence

The comparability of QUANTA LiteTM ß2 GPI IgM and Varelisa B2-Glycoprotein I IgM 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 B2-Glycoprotein I IgM Antibodies Assay is substantially equivalent to the predicate device, INOVA QUANTA Lite™ B2 GPI IgM Assay, and that the new 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 and Human Services. The logo features a stylized eagle with three tail feathers, representing the department's commitment to health, human services, and well-being. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

MAY 1 1 2004

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

K040451 Rc:

Trade/Device Name: Varelisa® ß2 Glycoprotein I IgM Antibodies Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MSV Dated: April 27, 2004 Received: April 30, 2004

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 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 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 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 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. Ardolett

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® ß2-Glycoprotein I IgM Antibodies - New Device 510(k) Submission Section 1. Indications for Use Statement

510(k) Number: KO40451

Device Name: Varelisa® ß2-Glycoprotein I IgM Antibodies

Intended Use Statement

The Varelisa ß2-Glycoprotein I IgM Antibodies EIA kit is designed for the semiquantitative and qualitative determination of ß2-glycoprotein I IgM antibodies in serum or plasma.

Mari Chan

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K040451

(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)

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).