AxSYM® Anti-CCP is a Microparticle Enzyme Immunoassay (MEIA) for the semiquantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum and plasma on the AxSYM System. 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 multicriterion diagnostic process, encompassing both clinical and laboratory-based assessments.

The AxSYM® Anti-CCP Standard Calibrators are for the standard calibration of the AxSYM System when used for the semi-quantitative determination the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum and plasma.

The AxSYM® Anti-CCP Controls are for the use in quality control to monitor the accuracy and precision of the AxSYM Anti-CCP assay when used for the semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum and plasma on the AxSYM System.

For in vitro diagnostic use.

Device Description

AxSYM Anti-CCP is based on Microparticle Enzyme Immunoassay (MEIA) technology. The AxSYM Anti-CCP reagents and sample are pipetted in the following sequence:

SAMPLING CENTER

. Sample and all AxSYM Anti-CCP reagents required for one test are pipetted by the Sampling Probe into various wells of a Reaction Vessel (RV),
AxSYM Line Diluent and sample are pipetted into the Incubation Well of the . RV.
. The AxSYM Anti-CCP Sample Diluent and diluted sample are pipetted into the Sample Well of the RV.
. The AxSYM Anti-CCP Matrix Cell Blocker is pipetted into the Buffer Well of the RV.
. The AxSYM Anti-CCP Mouse Anti-Human IgG:Alkaline Phosphatase Conjugate is pipetted into Reagent Well 3 of the RV.
. AxSYM Line Diluent and CCP-Coated Microparticles are pipetted into Reagent Well 2 of the RV.
. A reaction mixture is formed by combining diluted sample and diluted microparticles coated with CCP in Reagent Well 1 of the RV.
. When anti-CCP antibody is present in the sample, it binds to the CCP-Coated Microparticles, forming antigen-antibody complexes on the microparticles.

The RV is immediately transferred into the Processing Center. Further pipetting is done in the Processing Center by the Processing Probe.

PROCESSING CENTER

. An aliquot of Matrix Cell Blocker is transferred to the Matrix Cell.
. An aliquot of the reaction mixture, containing microparticles and bound antigen-antibody complex, is transferred to the Matrix Cell. The microparticles bind irreversibly to the glass fiber matrix.
The Matrix Cell is washed to remove materials not bound to the . microparticles.
The AxSYM Anti-CCP Mouse Anti-Human IgG:Alkaline Phosphatase . Conjugate is dispensed onto the Matrix Cell and it binds with the antigenantibody complexes.
. The Matrix Cell is washed to remove conjugate not bound to the microparticles.
. The substrate, 4-Methylumbelliferyl Phosphate, is added to the Matrix Cell. The alkaline phosphatase-labeled conjugate catalyzes the removal of a phosphate group from the substrate, yielding the fluorescent product, 4-Methylumbelliferone. This fluorescent product is measured by the MEIA optical assembly.

AI/ML Overview

Here's an analysis of the provided text regarding the AxSYM® Anti-CCP device, focusing on acceptance criteria and supporting study details:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are not explicitly stated in numerical thresholds within the provided text. Instead, the submission claims substantial equivalence to a predicate device (DIASTAT™ Anti-CCP Assay, K023285) based on comparable performance metrics.

Performance Metric	Acceptance Criteria (Implied by Substantial Equivalence)	Reported AxSYM® Anti-CCP Performance
Method Comparison	Comparable performance to predicate device	97.3% concordance with DIASTAT™ Anti-CCP
ROC AUC	Comparable AUC to predicate device	0.875
Precision	Substantially equivalent to predicate device	Demonstrated substantial equivalence
Linearity	Substantially equivalent to predicate device	Demonstrated substantial equivalence
Interferences	Substantially equivalent to predicate device	Demonstrated substantial equivalence
Stability	Substantially equivalent to predicate device	Demonstrated substantial equivalence

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

Sample Size: The document does not explicitly state the total number of samples used for the clinical performance comparison. It only mentions "all samples tested" for the method comparison with 97.3% concordance, but the raw count is not provided.
Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective.

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

This information is not provided in the document. The "ground truth" for evaluating the clinical performance of the AxSYM® Anti-CCP assay against the predicate device would typically involve a definitive diagnosis of Rheumatoid Arthritis (RA) or healthy controls, which should be established by qualified medical professionals. However, the document does not detail how this ground truth was established or the experts involved.

4. Adjudication Method for the Test Set

The document does not describe any adjudication method used for the test set.

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

Was an MRMC study done? No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This submission focuses on the performance of an in vitro diagnostic (IVD) assay, not a device requiring human interpretation of images or other data where reader variability would be a primary concern. The comparison is between two automated assays.
Effect size of human readers with/without AI assistance: Not applicable, as this was not an MRMC study involving human readers and AI assistance.

6. Standalone Performance Study

Yes, a standalone performance study was implicitly done for the AxSYM® Anti-CCP assay. The "Summary of Clinical Performance" directly reports on the performance of the AxSYM® Anti-CCP assay (e.g., its ROC AUC of 0.875) and compares it to the predicate device. This evaluation of the device's accuracy in distinguishing between patient populations is a form of standalone performance assessment.

7. Type of Ground Truth Used

The ground truth used for evaluating the clinical performance of the AxSYM® Anti-CCP assay (and the predicate DIASTAT™ Anti-CCP assay) would be the clinical diagnosis of Rheumatoid Arthritis (RA) and non-RA status of the patient samples. While the document doesn't explicitly state "pathology" or "outcomes data," the intended use as "an aid in the diagnosis of Rheumatoid Arthritis" implies that the samples used for validation were from individuals with confirmed RA and appropriate control groups.

8. Sample Size for the Training Set

The document does not report the sample size used for the training set. This submission is for a manufactured diagnostic kit, and the specifics of its internal algorithm development (including training data for the assay's cut-off determination or internal calibration) are not detailed.

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

The document does not report how the ground truth for the training set was established, as details about the device's internal development process are not included in this 510(k) summary.

Summary

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K063347

ADMIN 3.0 AxSYM® Anti-CCP 510(K) SUMMARY MAR 2 0 2007 (Summary of Safety and Effectiveness)

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

Submission Date: 03 Nov 2006

Dr Erica Conway Regulatory Affairs Manager

Axis-Shield Diagnostics, Ltd.

The Technology Park

Dundee DD2 1XA, Scotland, UK

Device Name: AxSYM® Anti-CCP

Reagents:

Classification Name: Antibodies, ANTI-CYCLIC CITRULLINATED PEPTIDE (CCP) Trade Name: AxSYM® Anti-Cyclic Citrullinated Peptide (Anti-CCP) Common Name: Anti-CCP test Governing Regulation: 866.5775 Device Classification: Class II Classification Panel: Immunology Product Code: NHX

Calibrators:

Classification Name: Calibrator, Secondary Trade Name: AxSYM® Anti-CCP Standard Calibrators

AxSYM Anti-CCP 510(k) Premarket notification submission ADMIN 4.0 510(k) Summary 03 Nov 2006 FINAL

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Common Name: Calibrator Governing Regulation: 862.1150 Device Classification: Class II Classification Panel: Clinical Chemistry Product Code: JIT

Controls:

Classification Name: Single (specified) analyte controls (assayed and unassayed) Trade Name: AxSYM® Anti-CCP Control Common Name: Control Governing Regulation: 862.1660 Device Classification: Class I Classification Panel: Clinical Chemistry Product Code: JJX

Legally marketed device to which equivalency is claimed:

DIASTAT™ Anti-CCP Assay (K023285)

Intended Use of Device:

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The AxSYM® Anti-CCP Controls are for the use in quality control to monitor the accuracy and precision of the AxSYM Anti-CCP assay when used for the semiquantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum and plasma on the AxSYM System.

Description of Device:

AxSYM Anti-CCP is based on Microparticle Enzyme Immunoassay (MEIA) technology. The AxSYM Anti-CCP reagents and sample are pipetted in the following sequence:

SAMPLING CENTER

. Sample and all AxSYM Anti-CCP reagents required for one test are pipetted by the Sampling Probe into various wells of a Reaction Vessel (RV),
AxSYM Line Diluent and sample are pipetted into the Incubation Well of the . RV.
. The AxSYM Anti-CCP Sample Diluent and diluted sample are pipetted into the Sample Well of the RV.
. The AxSYM Anti-CCP Matrix Cell Blocker is pipetted into the Buffer Well of the RV.
. The AxSYM Anti-CCP Mouse Anti-Human IgG:Alkaline Phosphatase Conjugate is pipetted into Reagent Well 3 of the RV.
. AxSYM Line Diluent and CCP-Coated Microparticles are pipetted into Reagent Well 2 of the RV.

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. A reaction mixture is formed by combining diluted sample and diluted microparticles coated with CCP in Reagent Well 1 of the RV.
. When anti-CCP antibody is present in the sample, it binds to the CCP-Coated Microparticles, forming antigen-antibody complexes on the microparticles.

The RV is immediately transferred into the Processing Center. Further pipetting is done in the Processing Center by the Processing Probe.

PROCESSING CENTER

. An aliquot of Matrix Cell Blocker is transferred to the Matrix Cell.
. An aliquot of the reaction mixture, containing microparticles and bound antigen-antibody complex, is transferred to the Matrix Cell. The microparticles bind irreversibly to the glass fiber matrix.
The Matrix Cell is washed to remove materials not bound to the . microparticles.
The AxSYM Anti-CCP Mouse Anti-Human IgG:Alkaline Phosphatase . Conjugate is dispensed onto the Matrix Cell and it binds with the antigenantibody complexes.
. The Matrix Cell is washed to remove conjugate not bound to the microparticles.
. The substrate, 4-Methylumbelliferyl Phosphate, is added to the Matrix Cell. The alkaline phosphatase-labeled conjugate catalyzes the removal of a phosphate group from the substrate, yielding the fluorescent product, 4-Methylumbelliferone. This fluorescent product is measured by the MEIA optical assembly.

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Comparison of Technological Characteristics:

AxSYM Anti-CCP is based on Microparticle Enzyme Immunoassay (MEIA) technology.

DIASTAT™ Anti-CCP is an enzyme-linked immunosorbent assay (ELISA).

Summary of Non-Clinical Performance:

The AxSYM® Anti-CCP assay is substantially equivalent to the DIASTAT™ Anti-CCP assay in terms of precision, linearity, interferences and stability as demonstrated in non-clinical performance data in this 510(k) submission.

Summary of Clinical Performance:

The AxSYM® Anti-CCP assay demonstrated substantially equivalent performance to the DIASTAT™ Anti-CCP indicated by a method comparison with 97.3 % concordance for all samples tested. A Receiver Operator Characteristic (ROC) curve analysis determined that the DIASTAT Anti-CCP and the AxSYM Anti-CCP assays' Area Under the Curve are 0.870 and 0.875, respectively. This analysis indicates that the two assays are comparable with respect to cut-off and specimen values.

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Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle or bird-like figure with three curved lines representing its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular fashion around the bird-like figure.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Axis-Shield Diagnostics Ltd c/o Ms. Erica Conway Regulatory Affairs Manager The Technology Park Dundee, Scotland DD2 1XA United Kingdom

MAR 2 0 2007

Re: K063347

Trade/Device Name: AxSYM® Anti-CCP Reagent Kit, AxSYM® Anti-CCP Standard Calibrator Kit and AxSYM® Anti-CCP Control Kit Regulation Number: 21 CFR 866.5775 Regulation Name: Rheumatoid factor immunological test system Regulatory Class: Class II Product Code: NHX, JIX, JJX, JJY Dated: February 23, 2007 Received: February 26, 2007

Dear Ms. Conway:

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). This letter will allow you to

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Page 2 -

begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, 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). 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 (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely vours.

Robert A. Becker f

Robert L. Becker, Jr., M.D., 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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ADMIN 5.0 Product Classification - Indications for Use

Statement

510(k) Number (if known): K 063347

Device Name: AxSYM® Anti-CCP Reagents, AxSYM® Anti-CCP Standard Calibrators (A-F) and AxSYM® Anti-CCP Controls (Positive and Negative)

Indications for Use:

Reagents

Calibrators

Controls

For in vitro diagnostic use.

Prescription Use

OR Over-The-Counter Use

(Part 21 CFR 801 Subpart D)

(21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Marie Chan
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

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AxSYM Anti-CCP 510(k) Premarket notification submission ADMIN 5.0 Indications for Use 02 Nov 2006 FINAL

510(k) Kol3347

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).