The Varelisa ReCombi ANA Screen EIA kit is designed for the qualitative determination of eight antinuclear antibodies in human serum or plasma (citrate/EDTA) to aid in the diagnosis of systemic rheumatic diseases such as SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/ dermatomyositis. The Varelisa ReCombi ANA Screen detects antibodies against dsDNA, UIRNP (RNP70, A, C), Sm, SS-A/Ro (52 kDa,60 kDa), SS-B/La, Scl-70, CENP-B and Jo-1 in a single microwell.

Device Description

The Varelisa ReCombi ANA Screen is an enzyme-linked immunosorbent assay (ELISA) for the qualitative determination of antinuclear antibodies in serum and plasma (citrate/EDTA). Designed as a screening assay, it detects eight antinuclear antibodies in a single microwell. The determination of antinuclear antibodies (ANA) is of central importance for the clinical diagnosis of rheumatic diseases. The presence of ANA suggests the possibility of rheumatic autoimmune diseases, These diseases include Systemic Lupus Erythemtosus (SLE), Polymyositis/ Dematomyositis, Scleroderma, Sjögren's Syndrome and Mixed Conective Tissue Diseases.

AI/ML Overview

The provided text does not contain a specific study designed to establish acceptance criteria for the Varelisa ReCombi ANA Screen device. Instead, it focuses on the device's substantial equivalence to a predicate device (K993108) and describes laboratory data supporting this equivalence. The FDA letter confirms the substantial equivalence determination but does not detail a separate study proving the device meets explicit acceptance criteria in the format requested.

Therefore, many of the requested fields cannot be directly populated from the provided documents.

Here's an analysis based on the available information:

1. Table of Acceptance Criteria and Reported Device Performance:

The document does not explicitly state quantitative acceptance criteria (e.g., specific sensitivity, specificity, or agreement thresholds) that the new device needed to meet. Instead, it relies on demonstrating comparable performance to the predicate device.

Acceptance Criteria	Reported Device Performance
Comparability to Predicate Device (Varelisa® ReCombi ANA Screen, K993108)	The document states that a comparison study analyzed 150 disease controls and 103 CTD samples. It concluded 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."
Detection of specific ANAs (dsDNA, U1RNP, Sm, SS-A/Ro, SS-B/La, Scl-70, CENP-B and Jo-1)	The device is designed for the qualitative determination of these eight antinuclear antibodies in human serum or plasma to aid in the diagnosis of systemic rheumatic diseases. The comparison study results for clinically defined sera and international reference sera would demonstrate this, though specific performance metrics are not given.
Performance with clinically defined sera and international reference sera	Results were obtained for these types of samples, supporting comparability to the predicate device. Specific performance values (e.g., sensitivity, specificity) are not provided.
Performance with samples from apparently healthy subjects (normal population)	Results were obtained for samples from apparently healthy subjects, supporting comparability to the predicate device. Specific performance values are not provided.

2. Sample size used for the test set and the data provenance:

Test Set Sample Size: "150 disease controls and 103 CTD samples."
Data Provenance: The document does not specify the country of origin. It indicates that the data includes "clinically defined sera and for international reference sera" and "samples from apparently healthy subjects (normal population)," suggesting a mix of sources. It's a retrospective analysis, comparing the new device's results to the predicate device and established serum characteristics.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This information is not provided in the document. The "ground truth" seems to be established by the clinical definition of the sera (e.g., "clinically defined sera," "disease controls," "CTD samples") and international reference sera.

4. Adjudication method for the test set:

This information is not provided in the document.

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:

This is not applicable. The device is an in vitro diagnostic (IVD) assay for qualitative determination of antibodies, not an AI-assisted diagnostic tool that humans would "read." It produces a quantitative result (OD at 450 nm and 620 nm) that is interpreted qualitatively.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

This is implicitly a standalone device. As an IVD assay, the device itself provides the result based on the biochemical reaction and optical density measurement. There isn't a "human-in-the-loop" component in the sense of a human interpreting complex images or data that the device first processes. The interpretation is of the assay's output.

7. The type of ground truth used:

The ground truth appears to be based on:

Clinical Diagnosis: For "clinically defined sera," "disease controls," and "CTD samples," the ground truth is their established clinical diagnosis.
International Reference Sera: These typically have well-characterized antibody profiles that serve as a ground truth for comparison.
Healthy Controls: Samples from "apparently healthy subjects" serve as a negative ground truth.

8. The sample size for the training set:

This information is not provided. The document describes a comparison study for validation of the new device's performance against the predicate, rather than a separate "training set" in the context of machine learning. The "development" of the new device (e.g., choice of recombinant antigens, synthetic peptides) would have occurred prior, potentially using other samples, but details are not given.

9. How the ground truth for the training set was established:

This information is not provided as a separate "training set" is not explicitly mentioned in the context of the performance validation study.

Summary

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510(K) SUMMARY OF SAFETY AND 9. EFFECTIVENESS

MAR ] 3 2009

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: K083188

Date of Summary Preparation:

Manufacturer: Phadia GmbH Munzinger Strasse 7 D-79111 Freiburg, Germany Company Contact Person: Martin Mann Regulatory Affairs Manager Phadia US Inc. 4169 Commercial Avenue Portage, MI 49002, USA +1 269 492 1957 (Phone) +1 269 492 7541 (Fax) martin.mann@phadia.com Device Name: Varelisa ReCombi ANA Screen Common Name: Antinuclear antibody immunological test system

Classification

Product Name	Product Code	Class	CFR
Varelisa® ReCombi ANA Screen	LJM	II	866.5100

Substantial Equivalence to

Varelisa® ReCombi ANA Screen:

510(k) number: K993108

Page 41

CONFIDENTIAL AND PROPRIETARY

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Intended Use Statement of the New Device

Intended use/Indication for use

The Varelisa ReCombi ANA Screen ElA kit is designed for the qualitative determination of eight antinuclear antibodies in human serum or plasma (citrate/EDTA) to aid in the diagnosis of systemic rheumatic diseases such as SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/ dermatomyositis. The Varelisa ReCombi ANA Screen detects antibodies against dsDNA, UIRNP (RNP70, A, C), Sm, SS-A/Ro (52 kDa,60 kDa), SS-B/La, Scl-70, CENP-B and Jo-1 in a single microwell.

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 Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of 8 antinuclear antibodies in serum or plasma (citrate/EDTA). The wells of a microplate are coated with human recombinant nuclear antigens, synthetic peptides and dsDNA. 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

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

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noncompetitive enzyme immunoassays for qualitative determination of IgG antibodies against antinuclear antigens 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 aids in the diagnosis of Connective Tissue Diseases such as SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis). MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and PM/DM (polymvositis/ dermatomyositis).

Differences do exist but do not affect the tenor of the "Intended Use" and do not raise new types of "Safety and Effectiveness" questions. The new device uses a synthetic peptide derived from the human SmD protein instead of Sm antigen purified from calf thymus. Minor differences pertain to increased volumina of the reagents and leaving out the prewashing step of the antigen strips. The Wash buffer no longer contains NaN3 and the substrate TMB is of lower concentration because the substrate incubation step has been increased to 30 min.

Laboratory equivalence

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

· results obtained for clinically defined sera and for international reference sera.
· results obtained for samples from apparently healthy subjects (normal population).
· Results obtained within a comparison study analyzing 150 disease controls and 103 CTD samples.

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/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo features a stylized eagle with its wings spread, facing to the right. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Phadia US Inc c/o Mr. Martin R. Mann Regulatory Affairs Manager 4169 Commercial Ave Portage, Michigan 49002

MAR 1 3 2009

Re: K083188 Trade/Device Name: Varelisa ® ReCombi ANA Screen Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: II Product Code: LJM Dated: October 24, 2008 Received: October 29, 2008

Dear Mr. Mann:

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 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). You may, therefore, market the device, subject to the general controls provisions of the Act. However, you are responsible to determine that the medical devices you use as components in the [kit/tray] have either been determined as substantially equivalent under the premarket notification process (Section 510(k) of the act), or were legally on the market prior to May 28, 1976, the enactment date of the Medical Device Amendments. Please note: If you purchase your device components in bulk (i.e., unfinished) and further process (e.g., sterilize) you must submit a new 510(k) before including these components in your kit/tray. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, and 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 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.

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Page 2- Mr. Mann

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.

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 s rotty premainteted 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 the labeling regulation, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240- 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For question regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR), please contact the Division of Surveillance Systems at 240-276-3464. You many obtain other general information on your responsibilities under the Act from the Division of Small Manufactuers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,
maria m chain

Maria M. Chan, Ph.D. 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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Indication for Use

510(k) Number (if known): K083188

Device Name:

Varelisa ReCombi ANA Screen

Indication For Use:

The Varelisa ReCombi ANA Screen EIA kit is designed for the qualitative determination of cight antinuclear antibodies in human serum or plasma to aid in the diagnosis of systemic rheumatic diseases such as SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/ dermatomyositis. The Varelisa ReCombi ANA Screen detects antibodies against dsDNA, U1RNP (RNP70, A, C), Sm, SS-A/Ro (52 kDa,60 kDa), SS-B/La, Scl-70, CENP-B and Jo-1 in a single microwell.

Prescription Use _ X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

im Chan

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) 083188

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).