AXIS-SHIELD ANTI-CCP

K110296 · Axis-Shield Diagnostics, Ltd. · NHX · Aug 18, 2011 · Immunology

Device Facts

• Record ID: K110296
• Device Name: AXIS-SHIELD ANTI-CCP
• Applicant: Axis-Shield Diagnostics, Ltd.
• Product Code: NHX · Immunology
• Decision Date: Aug 18, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5775
• Device Class: Class 2

Intended Use

The Axis-Shield Anti-CCP test is a semi-quantitative/qualitative enzyme-linked immunosorbent assay (ELISA) for the detection of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum (including Serum Separator Tubes) or plasma (EDTA, lithium heparin, or sodium citrate). Detection of anti-CCP antibodies is used as an aid in the diagnosis of rheumatoid arthritis (RA), and should be used in conjunction with other clinical information. Autoantibody levels represent one parameter in a multi-criterion diagnostic process, encompassing both clinical and laboratory-based assessments. For in vitro diagnostic use.

Device Story

Axis-Shield Anti-CCP is an ELISA-based in vitro diagnostic test for detecting IgG autoantibodies against cyclic citrullinated peptide in human serum or plasma. The device utilizes microtitre plates coated with synthetic CCP; patient samples are incubated, allowing specific autoantibodies to bind. Bound antibodies are detected via an enzyme-labeled anti-human IgG conjugate and TMB substrate, producing a colorimetric reaction measured by absorbance. The assay provides semi-quantitative results via interpolation from a dose-response curve or qualitative results via comparison to a reference control. Used in clinical laboratory settings by trained personnel. Results assist clinicians in the multi-criterion diagnosis of Rheumatoid Arthritis alongside other clinical and laboratory assessments.

Clinical Evidence

Clinical performance was evaluated using 514 retrospective serum samples (229 RA patients, 150 healthy, 135 non-RA disease). Using a 5.0 U/mL cutoff, the device showed 99.4% positive agreement and 98.8% negative agreement with the predicate. Clinical sensitivity for all RA was 78% (95% CI: 88.19-95.63%), with 63% for early RA and 82% for established RA. Clinical specificity was 99.3% in healthy asymptomatic donors and 97.8% in non-RA disease states (e.g., SLE, Sjögren’s, Hashimoto’s).

Technological Characteristics

Enzyme-linked immunosorbent assay (ELISA). Components: microtitre plates coated with synthetic cyclic citrullinated peptide, calibrators, positive/negative controls, goat anti-human IgG horseradish peroxidase conjugate, TMB substrate, sample diluent, wash buffer, and stop solution. Detection principle: colorimetric absorbance measurement.

Indications for Use

Indicated for use as an aid in the diagnosis of rheumatoid arthritis (RA) in patients suspected of having the disease. For prescription use only.

Regulatory Classification

Identification

A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.

Predicate Devices

• Diastat™ Anti-CCP assay (k023285)

Submission Summary (Full Text)

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# 510(k) Summary

AUG 1 8 2011

.

### Enter your 510(k) Summary or Statement.

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: _______________________________________________________________________________________________________________________________________________

#### Submission correspondent:

Dr Claire Dora RA Manager Axis-Shield Diagnostics Ltd. The Technology Park Dundee DD2 1XA, UK

## Device Name: Axis-Shield anti-CCP

### Reagents:

Classification Name: Antibodies, ANTI-CYCLIC CITRULLINATED PEPTIDE (CCP) Trade Name: Axis-Shield Anti-CCP Common Name: Anti-CCP test Governing Regulation: 866.5775 Device Classification: Class II Classification Panel: Immunology (82) Product Code: NHX, Antibodies, ANTI-CYCLIC CITRULLINATED PEPTIDE (CCP)

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# Legally marketed device to which equivalency is claimed:

DIASTAT™ Anti-CCP Assay (K023285)

## Intended Use of Device:

The Axis-Shield Anti-CCP test is a semi-quantitative/qualitative enzyme-linked immunosorbent assay (ELISA) for the detection of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum (including Serum Separator Tubes) or plasma (EDTA, lithium heparin, or sodium citrate). Detection of anti-CCP antibodies is used as an aid in the diagnosis of Rheumatoid Arthritis (RA), and should be used in conjunction with other clinical information. Autoantibody levels represent one parameter in a multi-criterion diagnostic process, encompassing both clinical and laboratory-based assessments. For in vitro diagnostic use.

## Indication(s) of Use:

Same as Intended Use

# Description of Device:

The Axis-Shield Anti-CCP device contains the following components:

a microtitre plate with 8 x 12-well breakapart strips coated with purified synthetic cyclic citrullinated peptide, in a resealable foil pack with desiccant; ready to use calibrators (diluent with or without IqG antibodies against CCP2); positive and negative assay controls (human plasma with or without IgG antibodies against CCP); ready-to-use reference control; goat anti-human IgG horseradish peroxidase conjugate: TMB substrate; sample diluent (5x) wash buffer (10x); ready-to-use stop solution.

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### Principle of the Assay:

The wells of the microtitre strips are coated with a highly purified synthetic cyclic citrullinated peptide containing modified arginine residues. During the first incubation, specific autoantibodies in diluted serum or plasma bind to the antigencoated surface. The wells are then washed to remove unbound components. In the second incubation, the Conjugate, an enzyme-labelled polyclonal antibody to human IgG, binds any surface-bound autoantibodies. After further washing, specific autoantibodies are traced by incubation with the Substrate. Addition of Stop Solution terminates the reaction, resulting in a coloured end-product. The amount of Coniugate bound is measured in absorbance units. In the qualitative protocol. the amount of Conjugate bound by the sample is compared with that bound by the Reference Control. In the semi-quantitative protocol, the concentration of anti-CCP autoantibody can be estimated by interpolation from a dose-response curve based on Calibrators.

### Comparison of Technological Characteristics:

The Axis-Shield Anti-CCP device is a semi-quantitative/qualitative enzyme-linked immunosorbent assay.

The predicate device, DIASTAT™ Anti-CCP is also an enzyme-linked immunosorbent assay.

## Summary of Non-Clinical Performance:

The Axis-Shield anti-CCP and DIASTAT™ Anti-CCP tests are enzyme-linked immunosorbent assays. The Axis-Shield Anti-CCP assay demonstrated substantially equivalent performance to the DIASTAT™ anti-CCP assay in terms of matrix comparison and assay interference as demonstrated by the non-clinical performance data included in this 510(k) submission.

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## Summary of Clinical Performance:

The Axis-Shield Anti-CCP assay demonstrated substantially equivalent clinical performance to the DIASTAT™ anti-CCP assay as indicated by a method comparison and concordance analysis, whereby 99 % concordance for all samples tested (n= 514) was demonstrated.

A Receiver Operator Characteristic (ROC) curve analysis (using the suggested cut-off of 5.0 U/mL) determined that the area under the curve (AUC) for the Axis-Shield anti-CCP assay was 0.910 (95% Confidence Interval: 0.881 to 0.940) and 0.903 (95% Confidence Interval: 0.871 to 0.934) for the DIASTAT™ anti-CCP assay. This analysis indicates that the two assays are comparable with respect to cut-off and clinical differentiation.

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Image /page/4/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a stylized caduceus, a symbol often associated with medicine and healthcare, with a single snake winding around a staff. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the caduceus. The seal is black and white.

Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Axis-Shield Diagnostics Limited c/o Dr. Claire I. Dora Regulatory Affairs Manager The Technology Park, Luna Place Dundee. Scotland United Kingdom DD2 1XA

AUG 1 8 20H

Re: k110296

Trade name: Axis-Shield Anti-CCP Regulation Number: 21 CFR §866.5775 Regulation Name: Rheumatoid factor immunological test system Regulatory Class: Class II Product Code: NHX Dated: July 19, 2011 Received: July 21, 2011

Dear Dr. Dora:

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 class II (Special Controls), 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); medical device reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of

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Page 2 – Dr. Claire Dora

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 advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

roti

P Reena Philip

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

#### (110296 510(k) Number (if known):

#### Device Name: Axis-Shield anti-CCP

Indication For Use:

The Axis-Shield Anti-CCP test is a semi-quantitative/qualitative enzyme-linked immunosorbent assay (ELISA) for the detection of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum (including Serum Separator Tubes) or plasma (EDTA, lithium heparin, or sodium citrate). Detection of anti-CCP antibodies is used as an aid in the diagnosis of Rheumatoid Arthritis (RA), and should be used in conjunction with other clinical information. Autoantibody levels represent one parameter in a multi-criterion diagnostic process, encompassing both clinical and laboratory-based assessments.

For in vitro diagnostic use.

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)

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

510(k) k110296