The Varelisa Sm Antibodies EIA kit is designed for the semiquantitative and qualitative determination of SmD antibodies in serum or plasma to aid in the diagnosis of systemic lupus erythematosus (SLE).

Device Description

The new device is an enzyme-linked immunosorbent assay (ELISA) using microtiter plates as the solid phase. The plate wells are coated with a synthetic SmD peptide as antigen, which allow anti-SmD antibodies to react with the immobilized antigen (sample). The conjugate is rabbit anti-human IgG horseradish peroxidase (HRP), which uses 3, 3'5, 5' tetramethylbenzidine dihydrochloride (TMB) as substrate. The kit contains a set of six calibrators, positive and negative controls. The kit also contains sample diluent, wash buffer concentrate and stop solution.

AI/ML Overview

The provided document is a 510(k) summary for Varelisa® Sm Antibodies, an in vitro diagnostic device, not an AI or medical imaging device. Therefore, many of the requested criteria such as sample size for test and training sets, number of experts, adjudication methods, multi-reader multi-case studies, and standalone performance are not applicable or typically reported in this type of submission.

However, I can extract information related to acceptance criteria and the study performed to demonstrate substantial equivalence to a predicate device.

Acceptance Criteria and Reported Device Performance

For in vitro diagnostic devices like the Varelisa® Sm Antibodies, acceptance criteria often revolve around demonstrating comparable performance (e.g., sensitivity, specificity, agreement) to a legally marketed predicate device. The document states that the new device is a successor to the predicate and that "all available data support that the new device is substantially equivalent to the predicate device and that the new device performs according to state-of-the-art expectations." While specific numerical performance values (e.g., sensitivity/specificity percentages) are not provided in this summary, the outcome of the study (comparability) serves as the "reported device performance."

Acceptance Criteria (Implied)	Reported Device Performance
Substantial equivalence to the predicate device (Varelisa® Sm Antibodies, K000312) in terms of efficacy and safety for its intended use.	Laboratory Equivalence Demonstrated: "The comparability of predicate device and new device is supported by a data set including:- results obtained within a comparison study analyzing positive, equivocal and negative sera.- results obtained for clinically defined sera and for international reference sera.- results obtained for samples from apparently healthy subjects (normal population).""In summary, all available data support that the new device is substantially equivalent to the predicate device and that the new device performs according to state-of-the-art expectations."

Acceptance Criteria (Implied)

Reported Device Performance

Substantial equivalence to the predicate device (Varelisa® Sm Antibodies, K000312) in terms of efficacy and safety for its intended use.

Laboratory Equivalence Demonstrated: "The comparability of predicate device and new device is supported by a data set including:- results obtained within a comparison study analyzing positive, equivocal and negative sera.- results obtained for clinically defined sera and for international reference sera.- results obtained for samples from apparently healthy subjects (normal population).""In summary, all available data support that the new device is substantially equivalent to the predicate device and that the new device performs according to state-of-the-art expectations."

Study Details:

Sample size used for the test set and the data provenance:
- Sample Size: Not explicitly stated in the provided text. The submission refers to a "data set" that included "positive, equivocal and negative sera," "clinically defined sera and for international reference sera," and "samples from apparently healthy subjects (normal population)." However, specific numbers for each group or total are not given.
- Data Provenance: Not explicitly stated, but the manufacturer is "Sweden Diagnostics (Germany) GmbH," suggesting European origin, though international reference sera would be globally sourced. The study appears to be retrospective as it uses collected sera.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not applicable to this type of in vitro diagnostic device. The "ground truth" for diagnostic kits is typically established by the clinical status of the patient (e.g., diagnosed with SLE or healthy) and/or by established reference methods or reference materials (like international reference sera), not by individual expert consensus on image interpretation.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable for this type of in vitro diagnostic device. Adjudication methods are relevant for subjective interpretations, often in imaging, to resolve discrepancies among experts. Clinical diagnoses and reference standards provide objective "ground truth."
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 is an in vitro diagnostic assay (laboratory test), not an AI-based system or a device that involves human readers or interpretation of cases in the context of AI assistance.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Not applicable. This is an in vitro diagnostic kit. The device itself performs the assay (detecting antibodies). The "performance" is the assay's ability to correctly identify the presence or absence of antibodies, which then aids a clinician in making a diagnosis. There isn't a "standalone algorithm" in the typical sense of AI. The device is the standalone diagnostic tool (in the context of laboratory analysis).
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth would be based on:
  - Clinical Diagnosis: For "clinically defined sera," the patient's existing clinical diagnosis of SLE or healthy status would serve as the ground truth.
  - Reference Standards: For "international reference sera," these are standardized biological materials with known characteristics, serving as a form of "ground truth."
  - Predicate Device Results (for comparison study): While not true ground truth, the predicate device's results would be used as a reference point for demonstrating comparability.
The sample size for the training set:
- Not applicable in the context of typical machine learning or AI device development for which this question is usually posed. This device is an immunoassay kit; it is wet-lab developed and validated, not "trained" on a data set in the computational sense.
How the ground truth for the training set was established:
- Not applicable, as there is no "training set" in the computational sense for this type of device. The assay's parameters (e.g., reagent concentrations, incubation times) are optimized through laboratory development, potentially using a different set of samples (often called "development" or "optimization" samples), but these are not "training sets" in the AI context.

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:	K042629
Date of Summary Preparation:	September 21, 2004
Manufacturer:	Sweden Diagnostics (Germany) GmbHMunzinger Strasse 7D-79111 Freiburg, Germany
Company Contact Person:	Sabine KlugbauerSpecialist, Regulatory AffairsSweden Diagnostics (Germany) GmbHMunzinger Strasse 7D-79111 Freiburg, Germany+49-761-47805-419(Phone)+49-761-47805-335 (Fax)
Device Name:	Varelisa® Sm Antibodies
Common Name:	Antinuclear antibodyimmunological test system

Classification

Product Name	Product Code	Class	CFR
Varelisa® Sm Antibodies	LKP	II	866.5100

Substantial Equivalence to

Varelisa® Sm Antibodies (510(k) number: K000312)

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Intended Use Statement of the New Device

Intended use/Indication for use

Special condition for use statement

The device is for prescription use only.

Special instrument requirements

A microplate reader capable of measuring OD at 450 mm and 620 nm is required.

General Description of the New Device

Test Principle of the New Device

The new device is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of SmD antibodies in human serum or plasma. The wells of a microplate are coated with a synthetic SmD peptide. Antibodies specific for SmD 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

The new device is developed as successor of the predicate device. Both assays share the same assay principle and indications for use. They are indirect noncompetitive enzyme immunoassays for the semiquantitative and qualitative determination of IgG antibodies against Sm in serum and plasma. Both assays recommend the same sample dilutions and use identical reagents (including the conjugate). The evaluation of the assays is identical. In accordance to the relevant scientific literature both assays state in the Intended Use, that the measuring of antibodies against Sm provides aid in the diagnosis of systemic lupus erythematosus (SLE).

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The new device is based on a synthetic peptide of the human SmD protein while the predicate device contains a native Sm protein isolated from calf thymus. Minor differences between the two devices pertain to the packaging size of the reagents and the leaving out of the prewashing step of the antigen strips.

Laboratory equivalence

The comparability of predicate device and new device is supported by a data set including

· results obtained within a comparison study analyzing positive, equivocal and negative sera.
· results obtained for clinically defined sera and for international reference sera.
results obtained for samples from apparently healthy subjects (normal population).

In summary, all available data support that the new device is substantially equivalent to the predicate device 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/12 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 U.S.A." arranged around the perimeter. Inside the circle is a stylized design featuring three abstract shapes that resemble birds in flight or flowing lines.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC - 8 2004

Sabine Klugbauer, Ph.D. Specialist, Regulatory Affairs Sweden Diagnostics (Germany) GmbH Munzinger Strasse 7 D-79111 Freiburg Germany

Re: K042629

Trade/Device Name: Varelisa® Sm Antibodies Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear Antibodies Immunological Test Systems Regulatory Class: Class II Product Code: LKP Dated: September 21, 2004 Received: September 27, 2004

Dear Dr. Klugbauer:

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 (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.

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Page 2 - Sabine Klugbauer, Ph.D.

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 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), please contact the Office of Compliance at (240) 276-3084. 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.qov/cdrh/dsma/dsmamain.html

Sincerely yours.

Robert L. Becker Jr.

Robert L. Becker, Jr., M.D., Ph. 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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Indications for Use

510(k) Number: K042629

Device Name:

Varelisa® Sm Antibodies

Indications For Use:

Maria Chan

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K042629

Prescription Use V (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Regulation Number and Section

§ 866.5100 Antinuclear antibody immunological test system.

(a)
Identification. An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).(b)
Classification. Class II (performance standards).