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 Description

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.

AI/ML Overview

Here's an analysis of the provided text, extracting the requested information about acceptance criteria and the supporting study:

The provided text describes a 510(k) submission for the Axis-Shield Anti-CCP device, claiming substantial equivalence to the DIASTAT™ Anti-CCP Assay. The primary study presented is a method comparison and concordance analysis between the two devices.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific numeric thresholds (e.g., "concordance must be >95%"). Instead, it presents the achieved performance and implies that this level of performance was considered "substantially equivalent" to the predicate.

Acceptance Criteria (Implied)	Reported Device Performance (Axis-Shield Anti-CCP vs. DIASTAT™ Anti-CCP)
Concordance	99% concordance for all samples tested (n=514)
Clinical Differentiation	Comparable with respect to cut-off and clinical differentiation, as indicated by ROC curve analysis: - Axis-Shield anti-CCP AUC: 0.910 (95% CI: 0.881 to 0.940) - DIASTAT™ anti-CCP AUC: 0.903 (95% CI: 0.871 to 0.934) (using suggested cut-off of 5.0 U/mL)

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

Sample Size for Test Set: 514 samples.
Data Provenance: Not explicitly stated (e.g., country of origin, demographics of participants). The document only mentions using "human serum (including Serum Separator Tubes) or plasma (EDTA, lithium heparin, or sodium citrate)." It's a clinical performance study comparing two assays, implying human samples. The study appears to be retrospective as it involves running existing banked samples on both devices for comparison.

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

The ground truth in this study is based on the results of the predicate device (DIASTAT™ Anti-CCP Assay). This is a comparison study, not a study aiming to establish the accuracy against a gold standard for Rheumatoid Arthritis diagnosis directly. Therefore, there were no human experts establishing a separate ground truth for the test set beyond the predicate device's results.

4. Adjudication Method for the Test Set

The concept of an adjudication method (like 2+1 or 3+1) is typically relevant when establishing a ground truth based on multiple expert opinions. Since the ground truth for comparison was the predicate device's results, no expert adjudication method was used for the test set. The devices were likely run independently and their results compared.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (ELISA assay), not an imaging-based AI system that requires human interpretation. Therefore, there is no "human readers improve with AI vs. without AI assistance" effect size to report.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the study primarily demonstrates the standalone performance of the Axis-Shield Anti-CCP device by comparing its output (antibody levels) directly to the predicate device's output. ELISA assays are inherently standalone tests; human involvement is in performing the lab procedure, not in interpreting the raw results in a way that would classify it as "human-in-the-loop" for the algorithm itself.

7. The Type of Ground Truth Used

The "ground truth" for the comparison study was the results obtained from the legally marketed predicate device (DIASTAT™ Anti-CCP Assay). While the intended use notes the test is an "aid in the diagnosis of Rheumatoid Arthritis (RA) and should be used in conjunction with other clinical information," the study itself does not directly use a definitive RA diagnosis (e.g., pathology, long-term outcomes, or consensus clinical diagnosis) as its ground truth for evaluation. Instead, it assumes the predicate's results are acceptable and compares the new device's results to them.

8. The Sample Size for the Training Set

The document does not provide information on a training set for the Axis-Shield Anti-CCP device. ELISA assays are typically developed through biochemical optimization and validation, not through machine learning training on a 'training set' in the conventional AI sense. The "clinical performance" study described is a validation or test set study for the finished device.

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

As there is no mention of a training set in the context of an algorithm requiring ground truth, this information is not applicable and not provided in the document.

Summary

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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:

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 (301) 796-5450. 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 (800) 638-2041 or (301) 796-7100 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:

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

Regulation Number and Section

§ 866.5775 Rheumatoid factor immunological test system.

(a)
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.(b)
Classification. Class II (performance standards).