(81 days)
The Varelisa ß2-Glycoprotein I IgA Antibodies EIA kit is designed for the semiquantitative and qualitative determination of ß2-glycoprotein I IgA 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.
The Varelisa B2-Glycoprotein I IgA Antibodies EIA kit is designed for the semiquantitative and qualitative determination of ß2-glycoprotein I IgA 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.
Here's an analysis of the provided text regarding the Varelisa® ß2 Glycoprotein I IgA Antibodies device, structured to address your specific questions about acceptance criteria and study details.
Please note: The provided text is a 510(k) summary, which often focuses on demonstrating substantial equivalence to a predicate device rather than presenting extensive de novo performance data with detailed acceptance criteria and standalone studies in the way a PMA might. As such, some of your requested information (e.g., specific quantitative acceptance criteria, standalone performance details, MRMC study results) is not explicitly present in the provided document. I will extract what is available and indicate when information is not provided.
Acceptance Criteria and Reported Device Performance
The provided 510(k) summary describes laboratory equivalence to a predicate device. It does not explicitly state quantitative acceptance criteria in a table format with specific thresholds. Instead, it relies on demonstrating comparable performance to the predicate device and expected behavior based on medical literature.
| Acceptance Criteria (Implied/General) | Reported Device Performance (Summary) |
|---|---|
| Comparability with Predicate Device (INOVA QUANTA Lite™ ß2 GPI IgA) | - Results obtained within a comparison study analyzing positive, equivocal, and negative sera showed comparability.- Results for externally defined calibrators showed comparability.- Results for samples from apparently healthy subjects (normal population) showed comparability. |
| Suitability for Serum and Plasma Samples | - The device is outlined for use with serum and plasma, with corresponding performance data underlining its effectiveness with plasma as a sample. |
| Performance in line with medical literature | - The assay performs as expected from the medical literature regarding the diagnosis of thrombotic disorders related to primary Antiphospholipid Syndrome or secondary to SLE/other autoimmune diseases. |
| Decision Point Evaluation Method | - The Varelisa assay uses an OD cutoff for evaluation, and corresponding performance data show the comparability of results to the predicate device which uses a decision point method. |
2. Sample Sizes and Data Provenance for Test Set
- Sample Size for Test Set: Not explicitly stated as a single number. The document mentions a "data set including results obtained within a comparison study analyzing positive, equivocal and negative sera," and "results obtained for samples from apparently healthy subjects (normal population)." The specific number of samples in these comparison studies is not detailed.
- Data Provenance: Not explicitly stated (e.g., country of origin). The studies appear to be clinical laboratory evaluations. The document refers to "the medical literature" and "scientific knowledge" as a basis for the intended use and performance expectations, implying a broader, though unspecified, provenance for general knowledge. The manufacturer is based in Germany.
- Retrospective/Prospective: Not explicitly stated. Given it's a 510(k) comparison study, it's often retrospective use of banked samples, but this is not confirmed.
3. Number of Experts and Qualifications for Ground Truth (Test Set)
This device is an in-vitro diagnostic (IVD) immunoassay for autoantibodies. The "ground truth" for such devices typically relies on a combination of:
- Clinical diagnosis based on established medical criteria (e.g., for SLE, Antiphospholipid Syndrome).
- Results from a well-characterized predicate immunoassay or reference method.
- Clinical status of patients (e.g., "apparently healthy subjects").
The document does not mention the use of human experts (e.g., radiologists) establishing ground truth in the way it would for an imaging AI device. The ground truth seems to be implicitly derived from the clinical status of the patients and the results of the predicate device.
4. Adjudication Method for Test Set
No explicit adjudication method is described. The "ground truth" for an immunoassay comparison study is usually established by the clinical diagnosis of the patient and/or the result from the predicate device (or a gold standard if available), rather than a panel of expert reviewers adjudicating individual results.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC study was done. This type of study (evaluating human reader performance with and without AI assistance) is relevant for imaging AI devices that assist human interpretation. This device is an immunoassay kit for laboratory use and does not involve human "readers" in the diagnostic interpretation in the same way.
6. Standalone (Algorithm Only) Performance Study
Yes, a standalone performance was done in the sense that the device's performance was evaluated independently and then compared to a predicate device. The comparison studies evaluating "positive, equivocal and negative sera," "externally defined Calibrators," and "samples from apparently healthy subjects" represent evaluations of the device's standalone performance characteristics against expected outcomes or the predicate device. However, a specific "standalone" performance metric like sensitivity/specificity against a definitive gold standard not involving the predicate is not explicitly presented, as the emphasis is on substantial equivalence.
7. Type of Ground Truth Used
The ground truth appears to be a combination of:
- Clinical Status/Diagnosis: The intended use links the presence of antibodies to aiding in the diagnosis of thrombotic disorders related to Antiphospholipid Syndrome, SLE, or other autoimmune diseases. Samples were collected from "apparently healthy subjects" and presumably patients with known clinical conditions.
- Predicate Device Results: The entire study is a "comparison study analyzing positive, equivocal and negative sera" in relation to the predicate device, thereby using the predicate device's established performance as a de facto reference for "truth" in the context of substantial equivalence.
8. Sample Size for the Training Set
This document does not specify a separate "training set" or its size. This is typical for traditional IVDs like immunoassays, where extensive "training" in the machine learning sense is not performed. Assay development involves optimizing reagents, protocols, and cutoffs, which are different from training an ML algorithm on a dataset. The studies described are more akin to verification and validation.
9. How Ground Truth for the Training Set Was Established
As there is no "training set" in the context of an AI/ML algorithm, this question is not applicable. The development and optimization of the immunoassay would rely on established laboratory practices, chemical principles, and clinical samples previously characterized by the predicate device or clinical diagnosis.
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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: | K040450 |
|---|---|
| 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 IgA Antibodies |
| Common Name: | B2 Glycoprotein I autoantibodyimmunological test system |
Classification
| Product Name | Product Code | Class | CFR |
|---|---|---|---|
| Varelisa® ß2 Glycoprotein I | MSV | II | 866.5560 |
Substantial Equivalence to
IgA Antibodies
INOVA QUANTA LITE™ ß2 GPI (IgA) Antibodies
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Intended Use Statement
The Varelisa B2-Glycoprotein I IgA Antibodies EIA kit is designed for the semiquantitative and qualitative determination of ß2-glycoprotein I IgA 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
The Varelisa B2-Glycoprotein I IgA Antibodies EIA kit is designed for the semiquantitative and qualitative determination of ß2-glycoprotein I IgA 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.
Varelisa® ß2-Glycoprotein I IgA Antibodies Test Principle
Varelisa B2-Glycoprotein I IgA Antibodies is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of B2glycoprotein I IgA antibodies in human serum or plasma. The wells of a microplate are coated with human purified B2-glycoprotein I antigen. 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
Both assays (the predicate and the new device) are indirect noncompetitive enzyme immunoassays for the semiquantitative and qualitative determination of 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 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 antiphospholipid syndrome. Thus the intended use of Varelisa ß2-glycoprotein I
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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 IgA is only recommended for use in serum specimen while the PHARMACIA Varelisa B2-glycoprotein I IgA 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 IgA assay is evaluated by using the decision point method. PHARMACIA Varelisa B2-glycoprotein I IgA 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 IgA and Varelisa ß2-Glycoprotein I 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. 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 IgA Antibodies Assay is substantially equivalent to the predicate device. INOVA OUANTA Lite™ ß2 GPI IgA 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 Department of Health & Human Services - USA. The logo features a stylized eagle with three lines representing its body and wings. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular fashion around the eagle.
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 Strassc 7 Freiburg, Germany D-79111
Rc: K040450
Trade/Device Name: Varelisa® ß2 Glycoprotein I IgA 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 Scction 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for usc 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 requircments as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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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
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Varelisa® B2 Glycoprotein I IgA Antibodies- Device Modification 510(k) Submission Section 1. Indications for Use Statement
510(k) Number:
510(k) Number: _______________________________________________________________________________________________________________________________________________________________
Device Name: Varelisa® ß2 Glycoprotein I IgA Antibodies
Intended Use Statement
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Mana Chan
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k)_ Ko 40455 _____________________________________________________________________________________________________________________________________________________________
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
V Prescription Use
OR
Over-The-Counter Use _________________________________________________________________________________________________________________________________________________________
(Per 21 CFR 801.109)
§ 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).