The Varelisa ReCombi ANA Profile EIA kit is designed for the qualitative determination of eight antinuclear antibodies in human serum or plasma to aid in the diagnosis of SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis and CREST syndrome), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/dermatomyositis. The Varelisa ReCombi ANA Profile individually detects antibodies against dsDNA, U1 RNP (RNP 70 kDa,A,C), SmD, SS-A/Ro(52 kDa, 60 kDa), SS-B/La, Scl-70, CENP-B and Jo-1.

Device Description

The new device is an enzyme-linked immunosorbent assay (ELISA) using microtiter plates as the solid phase. Plate wells each coated with 1 of 8 different ANA antigens are included to allow corresponding antibodies in the patient samples react with the immobilized antigens. 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 calibrator and a negative control. The kit also contains sample diluent, wash buffer concentrate and stop solution.

AI/ML Overview

Here's an analysis of the acceptance criteria and study information based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text does not explicitly state numerical acceptance criteria for the Varelisa ReCombi ANA Profile. Instead, it focuses on demonstrating "substantial equivalence" to predicate devices through comparability studies. Therefore, reported device performance is framed in terms of agreement with predicate devices and established reference standards.

Criterion Type	Acceptance Criteria (Explicitly Stated in Document)	Reported Device Performance
Comparability (General)	Substantial equivalence to predicate device.	"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."
Agreement with Predicate (New vs. K993109)	Qualitative determination of IgG antibodies against seven antinuclear proteins and dsDNA, recommending same sample dilutions and using identical reagents.	Both assays are indirect noncompetitive enzyme immunoassays for the qualitative determination of IgG antibodies against seven antinuclear proteins and dsDNA. Both recommend the same sample dilutions and use identical reagents (including the conjugate). The difference is the use of a synthetic SmD peptide instead of native Sm antigen.
Agreement with Predicate (New SmD vs. K042629)	Qualitative determination of IgG antibodies against SmD antigens, recommending same sample dilutions and using identical reagents and solid phase.	Both assays are indirect noncompetitive enzyme immunoassays for the qualitative determination of IgG antibodies against SmD antigens. Both recommend the same sample dilutions and use identical reagents (including the conjugate). The solid phase used in the new device is identical to the solid phase used in the predicate device.
Laboratory Equivalence	Demonstrating comparability via analysis of positive, equivocal, and negative sera, international reference sera, and samples from apparently healthy subjects.	Comparability is supported by: - results obtained within a comparison study analyzing positive, equivocal, and negative sera. - results obtained for international reference sera. - results obtained for samples from apparently healthy subjects (normal population).

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

The document mentions "a comparison study analyzing positive, equivocal and negative sera" and "samples from apparently healthy subjects (normal population)" but does not specify the exact sample size for the test set or the country of origin of the data. It can be inferred that the data is retrospective as it refers to a "comparison study" and "available data," suggesting pre-collected samples.

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

The document does not specify the number of experts used or their qualifications for establishing ground truth. The nature of the device (an immunoassay for antibody detection) suggests that ground truth would likely be established through clinical diagnosis of autoimmune diseases or by established reference methods for antibody detection, rather than expert interpretation of images or complex data.

4. Adjudication Method for the Test Set

The document does not provide information on any adjudication method used for the test set.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is more relevant for diagnostic devices that rely on human interpretation of images or complex data, where the AI might assist a reader. The Varelisa ReCombi ANA Profile is an automated immunoassay where the output is a qualitative determination (positive/negative) based on optical density readings, not a human interpretation task.

6. Standalone (Algorithm Only) Performance Study

Yes, a standalone performance study was done implicitly. The entire evaluation described for the Varelisa ReCombi ANA Profile relates to its performance as a standalone assay, comparing its results directly to predicate devices and reference materials. The device is the algorithm, producing results without human-in-the-loop assistance for interpretation of the test itself.

7. Type of Ground Truth Used

The ground truth used appears to be a composite of:

Clinical Diagnosis: The intended use states the kit "aids in the diagnosis of SLE... scleroderma... MCTD... SS and polymyositis/dermatomyositis," implying that patient samples from individuals with confirmed diagnoses of these conditions would serve as ground truth for "positive" samples.
Established Reference Materials: The study mentions "results obtained for international reference sera," indicating that recognized standard antibody preparations were used as ground truth.
Predicate Device Results (as a gold standard proxy): A significant part of the study involves comparing the new device's results to those obtained with the predicate devices for positive, equivocal, and negative sera. This suggests the predicate device's performance served as a de-facto "ground truth" for demonstrating equivalence.
Healthy Controls: "Samples from apparently healthy subjects (normal population)" were used to establish negative ground truth.

8. Sample Size for the Training Set

The document does not mention a training set or its sample size. This is typical for a traditional immunoassay device. "Training" in the context of an AI/ML device would refer to the data used to develop the algorithm. For this device, the "algorithm" is the biochemical assay itself and its reading protocol, not a machine learning model that learns from large datasets. The development process would involve optimization and validation runs rather than distinct "training" and "test" sets in the AI sense.

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

As no training set is mentioned in the AI/ML context, this question is not applicable. The "ground truth" for the development of the assay would have been established through a combination of chemical and biological principles, known antibody-antigen reactions, and clinical validation against diagnosed patient samples and controls, rather than a specific "ground truth for a training set."

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.

and the comments of the comments of the country of the country of

Assigned 510(k) Number:	K050625
Date of Summary Preparation:	March 08, 2005
Manufacturer:	Sweden Diagnostics (Germany) GmbHMunzinger Strasse 7D-79111 Freiburg, Germany
510 (K) 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® ReCombi ANA Profile
Common Name:	Antinuclear antibodyimmunological test system

Classification

Product Name	Product Code	Class	CFR
Varelisa® ReCombiANA Profile	LJM	II	866.5100

Substantial Equivalence to

Varelisa® ReCombi ANA Profile (510(k) number: K993109) Varelisa® Sm Abs (510(k) number: K042629)

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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 nm and 620 nm is required.

General Description of the New Device

Test Principle of the New Device

Varelisa ReCombi ANA Profile is an indirect noncompetitive enzyme immunoassay for the individual qualitative determination of dsDNA, U1 RNP (RNP 70 kDa, A, C), Sm (D), SS-A/Ro (52 kDA, 60 kDA), SS-B/La, Scl-70, CENP-B and Jo-1 antibodies in serum or plasma. The wells of a microplate are coated with human recombinant antigens, synthetic peptides or plasmid DNA. Antibodies specific for the nuclear antigens present in a patient sample bind to these nuclear antigens.

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

Varelisa ReCombi ANA Profile (Art No 12996) vs (Art No 18496)

The new device is developed as successor of the predicate device Varelisa ReCombi ANA Profile (Art No 12996). Both assays are indirect noncompetitive

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enzyme immunoassays for the qualitative determination of IgG antibodies against seven antinuclear proteins and dsDNA in serum and plasma. Both assays recommend the same sample dilutions and use identical reagents (including the conjugate). In accordance to the relevant scientific literature both assays state in the Intended Use, that the measuring of antinuclear antibodies provides aid in the diagnosis of SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis and CREST syndrome), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/ dermatomyositis.

The difference between the assays is the use of a synthetic peptide derived from the human SmD protein instead of internally produced native Sm antigen (complex consisting of SmBB' and SmD) purified from calf thymus. Further information on the synthetic SmD peptide is given in the submission of the quantitative assay Varelisa Sm Abs (K042629). For additional information of the customer an "Included Information Sheet" will be performed (see Chapter 4.5). Minor differences pertain to different volumes of the reagents.

Varelisa Sm Abs (Art No 18296) vs ReCombi ANA Profile (Art No 18496)

The new device and the predicate device Varelisa Sm Abs, both are indirect noncompetitive enzyme immunoassays for the qualitative determination of IgG antibodies against SmD antigens. Both assays recommend the same sample dilutions and use identical reagents (including the conjugate). The solid phase strip used in the new devise is identical to the solid phase used in the predicate device. In accordance to the relevant scientific literature both assays state in the Intended Use, that the measuring of SmD antibodies in serum or plasma aids in the diagnosis of systemic lupus erythematosus (SLE).

Laboratory equivalence

The comparability of predicate devices 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 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 seal for the Department of Health & Human Services. The seal is circular, with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" written around the perimeter of the circle. Inside the circle is an abstract image of an eagle.

Public Health Service

APR 2 6 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

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

Re: K050625

Trade/Device Name: Valelisa® ReCombi ANA Profile Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear Antibodies Immunological Test System Regulatory Class: Class II Product Code: LJM Dated: March 8, 2005 Received: March 11, 2005

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 (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 -- 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) 276-0131. 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,

Robert H. Becker

Robert L. Becker, Jr., M.D., A 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: K050625

Device Name:

Varelisa® ReCombi ANA Profile

Indications For Use:

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)

mana m Carrellis

Concurrence of CDRH Office of Device Evaluation (ODE) Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) Kosogins
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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).