The Varelisa B .- Glycoprotein I Antibodies Screen EIA kit is designed for the qualitative determination of B2-Glycoprotein I antibodies in human 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.

Device Description

The Varelisa ß2-Glycoprotein I Antibodies Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of antibodies against ß glycoprotein I in serum or plasma.

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

AI/ML Overview

The provided text describes a 510(k) summary for a medical device called Varelisa® ß2-Glycoprotein I Antibodies Screen. While it discusses the device's intended use and general performance, it does not explicitly state formal acceptance criteria in a quantifiable manner or detail a specific study designed to "prove" the device meets such criteria to the extent typically expected in a scientific study report.

Instead, the document focuses on demonstrating substantial equivalence to a predicate device (INOVA QUANTA Lite™ B2 GPI Screen) through comparative performance data. The "study" mentioned is a "comparison study analyzing positive, equivocal and negative sera," along with results for external calibrators and samples from healthy subjects.

Here's an attempt to extract the requested information based on the provided text, acknowledging limitations due to the nature of the 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

As specific quantitative acceptance criteria (e.g., minimum sensitivity, specificity, or agreement percentages) are not explicitly stated in the provided text, this table will represent the general comparative findings presented to establish substantial equivalence.

Acceptance Criterion (Inferred from Substantial Equivalence Goal)	Reported Device Performance (Varelisa® ß2-Glycoprotein I Antibodies Screen vs. Predicate)
Qualitative determination of B2-Glycoprotein I antibodies in human serum.	The new device is "substantially equivalent" to predicate for qualitative determination in serum.
Qualitative determination of B2-Glycoprotein I antibodies in human plasma.	Performance data "underline the effectiveness of the assay with plasma as sample," unlike the predicate which is "only recommended for use in serum."
Comparability with predicate device across positive, equivocal, and negative sera.	"The comparability... is supported by a data set including results obtained within a comparison study analyzing positive, equivocal and negative sera."
Performance with externally defined Calibrators.	"Results obtained for externally defined Calibrators" support comparability.
Performance with samples from apparently healthy subjects (normal population).	"Results obtained for samples from apparently healthy subjects (normal population)" support comparability.
Performance according to current scientific knowledge regarding B2-glycoprotein I antibodies and antiphospholipid syndrome.	"Intended use... was adapted to the current state of scientific knowledge." The device "performs as expected from the medical literature."
OD cut-off method for evaluation.	"Corresponding performance data show the comparability of the results" with the predicate's decision point method.

Note: The document states, "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." This implies that the 'acceptance criteria' were met by demonstrating similar performance to the legally marketed predicate and suitability for both serum and plasma.

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

Test Set Sample Size: Not explicitly stated. The text mentions "a comparison study analyzing positive, equivocal and negative sera," "results obtained for externally defined Calibrators," and "results obtained for samples from apparently healthy subjects (normal population)." However, the specific number of samples in each category tested is not provided.
Data Provenance: Not explicitly stated (e.g., specific country of origin or whether samples were prospective or retrospective). The manufacturer is based in Germany, so it's plausible the data collection predominantly occurred there or in Europe, but this is not confirmed. The study used "human serum or plasma."

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

This information is not provided in the document. For immunological assays like this, ground truth is typically established by clinical diagnosis, other laboratory tests, or established consensus among medical professionals. The document simply states the device aids in diagnosis "in conjunction with clinical findings and other laboratory tests."

4. Adjudication Method for the Test Set

This information is not provided. The text does not describe any expert adjudication process for the test results.

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

No. The device is an in-vitro diagnostic (IVD) immunoassay designed for qualitative determination of antibodies, not an imaging device typically assessed with MRMC studies or involving human readers interpreting outputs in such a way. The focus is on the device's accuracy in detecting specific antibodies rather than human interpretation of complex data. Therefore, there is no mention of human readers or an effect size for human improvement with AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes. The data presented appears to refer to the standalone performance of the Varelisa® ß2-Glycoprotein I Antibodies Screen device itself, comparing its output to that of the predicate device and potentially to clinical expectations. As an automated immunoassay, its performance is inherently standalone in generating a result, which is then interpreted by a clinician in the context of other findings.

7. Type of Ground Truth Used

The type of ground truth used is not explicitly detailed for the specific comparison study. However, for an immunoassay, the implicit ground truth would typically be established based on:

Clinical diagnosis: Patients with primary Antiphospholipid Syndrome or SLE.
Other laboratory tests: Results from established assays for B2-glycoprotein I antibodies or other relevant markers.
Disease status: Classification of samples as "positive, equivocal and negative sera" implies a prior determination of their status, likely based on a combination of clinical criteria and/or predicate device results.

8. Sample Size for the Training Set

The document is a 510(k) summary for an immunoassay kit. Immunoassays are typically "trained" during their development and optimization phases, but the process is different from machine learning algorithms. The text does not provide any information about a "training set" or its size in the context of device development or any potential algorithm used.

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

As there is no mention of a training set in the provided text in the context of a machine learning algorithm, there is no information on how its ground truth would have been established. For traditional immunoassay development, the "ground truth" for calibrator and control materials is established through rigorous internal characterization and standardization, often against reference materials. However, details of this are not included here.

Summary

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

ழ். 510(K) SUMMARY OF SAFETY AND 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:	K040452
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 Antibodies Screen
Common Name:	B2-Glycoprotein I autoantibodyimmunological test system

Classification

Product Name	Product Code	Class	CFR
--------------	--------------	-------	-----

Varelisa® ß2-Glycoprotein I MSV ロ 866.5660 Antibodies Screen

Substantial Equivalence to

INOVA QUANTA Lite™ B2 GPI Screen

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

Intended Use Statement

The Varelisa B .- Glycoprotein I Antibodies Screen EIA kit is designed for the qualitative determination of B2-Glycoprotein I antibodies in human serum or plasma.

General Description of the Device

The Varelisa ß2-Glycoprotein I Antibodies Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of antibodies against ß glycoprotein I in serum or plasma.

Varelisa® ß2-Glycoprotein I Antibodies Screen Test Principle

Varelisa B2-Glycoprotein I Antibodies Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of B2-glycoprotein I (IgG/IgM/IgA) antibodies in human serum or plasma. The wells of a microplate are coated with B2-glycoprotein I. Antibodies specific for B2-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

INOVA QUANTA Lite™ ß2 GPI Screen (the predicate device) and PHARMACIA Varelisa B2-glycoprotein I Antibodies Screen (the new device) both are indirect noncompetitive enzyme immunoassays for qualitative detection of IgM, IgG and IgA antibodies against B2-glycoprotein I in serum. Both assays recommend the same sample dilutions and use comparable enzyme-linked conjugates and antigens.

Based on currently available data from the literature the measuring of the antibodies against ß2-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

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

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™ B2 GPI Screen is only recommended for use in serum specimen while the PHARMACIA Varelisa B2-glycoprotein I Antibodies Screen 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 Screen contains an additional assay control and the assay is evaluated by using the decision point method. PHARMACIA Varelisa B2-glycoprotein I Antibodies Screen assay uses an ODcut-off. Corresponding performance data show the comparability of the results.

Laboratory equivalence

The comparability of INOVA QUANTA Lite™ ß2 GPI Screen and PHARMACIA Varelisa ß2-glycoprotein I 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. 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 Antibodies Screen Assay is substantially equivalent to the predicate device, INOVA QUANTA Lite™ ß2 GP1 Screen Assay, and that the new 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 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" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, resembling a bird-like shape.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

MAY 11 2004

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

Re: K040452

Trade/Device Name: Varelisa® ß2 Glycoprotein I Antibodies Screen 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).

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

Page 2

This letter will allow you to begin marketing your device as described in your Section 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 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. Hackett

Joseph L. Hackett, Ph.D. Acting Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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

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

510(k) Number:

K040452

Device Name: Varelisa® ß2-Glycoprotein I Antibodies Screen

Intended Use Statement

The Varelisa 32-Glycoprotein I Antibodies Screen EIA kit is designed for the qualitative determination of $2-Glycoprotein I antibodies in human 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.

Thana Chan

ion Sign-C

Office of In Vitro Diagnostic Device Evaluation and Safety

510(K) K040452

(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).