K Number
K093908
Device Name
CCPOINT
Date Cleared
2010-12-01

(344 days)

Product Code
Regulation Number
866.5775
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The Euro-Diagnostica CCPoint® test is a visually read, qualitative rapid lateral flow test for the detection of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human serum or plasma. The results of the test are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. For use by trained laboratory professionals. For in vitro diagnostic use.

Device Description

The Euro-Diagnostica CCPoint® test is a visually read, qualitative rapid lateral flow test for the detection of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human serum or plasma. The results of the test are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. For use by trained laboratory professionals. For in vitro diagnostic use.

The CCPoint® test is a colloidal gold based lateral flow immunoassay. Reactive cyclic citrullinated peptides are immobilised as a discrete line on a porous membrane located in the test zone.

The detection reagent, consisting of colloidal gold particles conjugated to anti-human IgG, is deposited within the device onto the conjugate pad.

In the assay procedure, a sample of serum or plasma is added to the sample port. A blood cell separation membrane transfers the sample fluid onto the porous membrane. After a short incubation running buffer is added to the buffer port. This buffer mobilizes the colloidal gold particles from the conjugate pad. The gold particles and the sample move by capillary force across the membrane.

If the sample contains anti-CCP antibodies they will bind to the peptide-antigens and a red line will appear in the test zone (marked T). If the sample does not contain any anti-CCP antibodies no line will appear. With any sample a red control line should appear in the control zone (marked C). The control ensures that the coated colloidal gold is still active.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the CCPoint® kit, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The submission primarily focuses on demonstrating substantial equivalence to a predicate device (Immunoscan RA anti-CCP test kit) and providing clinical performance metrics. Explicit "acceptance criteria" for the CCPoint® beyond achieving substantial equivalence and acceptable clinical performance are not explicitly stated as numerical targets in the same way one might see for a completely novel device claim. However, the reported performance serves as the basis for the FDA's substantial equivalence determination.

Implied Acceptance Criteria / Performance Benchmarks (derived from the predicate comparison and clinical performance):

Performance MetricAcceptance Criteria (Implied)Reported Device Performance (CCPoint®)
Agreement with Predicate Device (Immunoscan RA anti-CCP):
Positive Percent Agreement (PPA)High PPA (e.g., >95% to demonstrate comparable positive results)99.6% (95% CI: 98.4 - 99.9%)
Negative Percent Agreement (NPA)High NPA (e.g., >95% to demonstrate comparable negative results)99.4% (95% CI: 98.3 - 99.8%)
Overall Percent Agreement (OPA)High OPA (e.g., >95% for overall concordance)99.4% (95% CI: 98.8 - 99.8%)
Clinical Performance:
Sensitivity (for RA patients)Clinically acceptable sensitivity (e.g., comparable to predicate or established diagnostic markers)73.5% (95% CI: 69.9 - 77.0%)
Specificity (Healthy Blood Donors)High specificity (e.g., >95% to minimize false positives)99.1% (95% CI: 97.8 - 99.8%)
Specificity (Non-RA Arthritis)High specificity (e.g., >95%)100% (95% CI: 98.0 - 100%)
Specificity (Spondylarthropathy)High specificity (e.g., >95%)100% (95% CI: 83.9 - 100%)
Specificity (Systemic Collagen Disease)High specificity (e.g., >95%)97.6% (95% CI: 93.2 - 99.5%)
Specificity (Vasculitis/PMR)High specificity (e.g., >95%)100% (95% CI: 93.9 - 100%)
Specificity (Degenerative Disease)High specificity (e.g., >95%)100% (95% CI: 95.3 - 100%)
Specificity (Pain Syndrome/Misc.)High specificity (e.g., >95%)98.2% (95% CI: 90.6 - 100%)
Specificity (Other non-RA autoimmune)High specificity (e.g., >95%)100% (95% CI: 92.7 - 100%)
Specificity (Infectious Diseases)High specificity (e.g., >95%)97.2% (95% CI: 92.1 - 99.4%)
Specificity (Routine samples not RA)High specificity (e.g., >95%)97.4% (95% CI: 91.2 - 99.7%)
Accuracy (Inter-assay & Batch-to-batch)100% agreement with expected results100% agreement with expected results

2. Sample Size and Data Provenance (Test Set)

  • Sample Size for Predicate Comparison (Table 1a): 1062 frozen retrospective sera.
    • 606 from RA patients
    • 456 apparently healthy blood donors
  • Sample Size for Predicate Comparison (Table 1b, subset): 399 samples (extracted from Table 1a, specifically those in the range of 15-1600 U/mL with the ELISA).
  • Sample Size for Clinical Sensitivity/Specificity (Table 2 & Specificity Tables): 1815 frozen retrospective sera with clinical characterization.
    • 596 patients with clinically defined RA
    • 456 Blood donors
    • 187 non-RA arthritis
    • 43 Psoriatic arthritis
    • ... (various other disease/control groups listed in the document, totaling 1815)
  • Data Provenance: "frozen retrospective sera". The country of origin is not explicitly stated in the provided text.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test set. It mentions "Patients with clinically defined RA" and "frozen retrospective sera with clinical characterisation," suggesting that clinical diagnoses and medical records were used to categorize samples. However, there's no detail on who made or confirmed these diagnoses, nor any adjudication process by experts specifically for the study.

4. Adjudication Method (Test Set)

No adjudication method (e.g., 2+1, 3+1) is mentioned or described for establishing the ground truth of the test set. The clinical characterization appears to be based on pre-existing diagnoses in the retrospective sera.

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

No MRMC comparative effectiveness study was done. The device is a visually read rapid diagnostic test, and the performance study described is an agreement study against a predicate device and a clinical sensitivity/specificity study against clinical diagnoses. It does not evaluate human readers' improvement with or without AI assistance.

6. Standalone Performance Study (Algorithm Only)

Yes, a standalone performance study was done. The CCPoint® is a visually read, qualitative rapid lateral flow test. The performance data presented (percent agreements, sensitivity, specificity) reflects the output of the device itself (the presence or absence of a red line) when interpreted visually according to its intended use instructions by trained laboratory professionals. There is no separate "algorithm" being assessed independent of the visual interpretation of the test result; the visual interpretation is the algorithm's output.

7. Type of Ground Truth Used

  • For Predicate Comparison (Tables 1a, 1b): The ground truth was established by the results of the predicate device, Immunoscan RA anti-CCP ELISA.
  • For Clinical Sensitivity and Specificity (Table 2 and subsequent specificity tables): The ground truth was "clinical characterization" or "clinically defined RA" for the RA patient group, and diagnostic categories (e.g., "Blood donors," "non-RA arthritis," "Systemic collagen disease") for the control and disease groups. This indicates clinical diagnoses/outcomes information as the ground truth.

8. Sample Size for the Training Set

The document does not mention a separate "training set" or "validation set" in the context of machine learning. This is a diagnostic device comparison and clinical performance study, not an AI/machine learning model development. Therefore, there's no reported sample size for a training set in that sense. The samples used for the performance evaluation are considered a test set.

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

As there is no mention of a traditional "training set" for an AI/ML model, this question is not applicable. The device's mechanism is a biochemical immunoassay, not a learning algorithm that requires a training phase.

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K093908

Summary of Safety and Effectiveness Information CCPoint® kit

DEC 1 2010

Euro-Diagnostica AB, Lundavägen 151, SE-212 24 Malmö, Sweden 1. Contact person: Ms. Annika Andersson Telephone: +46 40 53 76 04 Fax: +46 40 43 22 88 Date of preparation: November 30, 2010

II. Device/Trade name: CCPoint® Common name: Anti-CCP test Governing regulation: 866.5775 Device classification: Class II Classification panel: Immunology Product code: NHX

III. Description of Device: The Euro-Diagnostica CCPoint® test is a visually read, qualitative rapid lateral flow test for the detection of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human serum or plasma. The results of the test are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. For use by trained laboratory professionals. For in vitro diagnostic use.

The CCPoint® test is a colloidal gold based lateral flow immunoassay. Reactive cyclic citrullinated peptides are immobilised as a discrete line on a porous membrane located in the test zone.

The detection reagent, consisting of colloidal gold particles conjugated to anti-human IgG, is deposited within the device onto the conjugate pad.

In the assay procedure, a sample of serum or plasma is added to the sample port. A blood cell separation membrane transfers the sample fluid onto the porous membrane. After a short incubation running buffer is added to the buffer port. This buffer mobilizes the colloidal gold particles from the conjugate pad. The gold particles and the sample move by capillary force across the membrane.

If the sample contains anti-CCP antibodies they will bind to the peptide-antigens and a red line will appear in the test zone (marked T). If the sample does not contain any anti-CCP antibodies no line will appear. With any sample a red control line should appear in the control zone (marked C). The control ensures that the coated colloidal gold is still active.

IV. Legally marketed device to which equivalence is claimed: Immunoscan RA anti-CCP test kit, K052133.

V. Intended use of the device: The Euro-Diagnostica CCPoint® test is a visually read, qualitative rapid lateral flow test for the detection of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human serum or plasma. The results of the test are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. For use by trained laboratory professionals. For in vitro diagnostic use.

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VI. Comparison of technological characteristics: CCPoint® is a qualitative rapid lateral flow test. Immunoscan RA anti-CCP is an enzyme-linked immunosorbent assay (ELISA).

Similarities

ltemDevicePredicate Device
CCPoint®Immunoscan RAanti-CCP
Intended useThe results of the test areto be used as an aid to thediagnosis of RheumatoidArthritis (RA), inconjunction with otherlaboratory and clinicalfindings.The results of the assayare to be used as an aidto the diagnosis ofRheumatoid Arthritis(RA), in conjunctionwith other laboratoryand clinical findings.
Intended userFor use by trainedlaboratory professionalsFor use by health careprofessionals
Type of testQualitativeQualitative and semi-quantitative
Analyte measuredAnti-CCPAnti-CCP
Coated antigenSynthetic CCPSynthetic CCP
ConjugateAnti-human IgGAnti-human IgG

Differences

ItemDevicePredicate Device
CCPoint®Immunoscan RAanti-CCP
MethodLateral flowELISA
Test matrixSerum and plasmaSerum
Type of testQualitativeQualitative and semi-quantitative
Sample dilutionUndilutedDiluted 1:50
Measuring of resultsVisually readELISA plate reader

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VI. Summary of performance: CCPoint® is substantially equivalent to the Immunoscan RA anti-CCP test kit. Equivalence is demonstrated by the following comparative results.

Table 1a. Percent agreement of the CCPoint® compared to the Immunoscan RA anti-CCP test kit. A total of 1062 frozen retrospective sera were assayed. 606 from RA patients and 456 samples were apparently healthy blood donors.

Predicate device(Immunoscan RA anti-CCP)
New deviceN = 1052PositiveNegative
CCPoint®Positive4444
Negative2612
Positive Percent Agreement:444/446 = 99.6%95% CI = 98.4 - 99.9%
Negative Percent Agreement:612/616 = 99.4%95% CI = 98.3 - 99.8%
Overall Percent Agreement:1056/1062 = 99.4%95% CI = 98.8 - 99.8%

Table 1b.Percent agreement of the CCPoint® compared to the Immunoscan RA anti-CCP test kit. Samples extracted from table 1a in the range 15-1600 U/mL with the ELISA

Predicate device(Immunoscan RA anti-CCP)
New deviceN = 399PositiveNegative
CCPoint®Positive3774
Negative216
Positive Percent Agreement:377/379 = 99.5%95% CI = 98.1 - 99.9%
Negative Percent Agreement:16/20 = 80.0%95% CI = 56.3 - 94.3%
Overall Percent Agreement:393/399 = 98.5%95% CI = 96.8 - 99.4%

The 95% confidence interval (CI) was calculated using the exact method.

Table 2. Clinical sensitivity and specificity. A total of 1815 frozen retrospective sera with clinical characterisation were assayed. The following table summarizes the results.

nnegativepositiveSensitivity
Patients with clinicallydefined RA59615843873.5%

Clinical sensitivity 95% Cl = 69.9 - 77.0% = 73.5% 438/596 RA

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Clinical specificity for the CCPoint® for non-RA diseased patients and
asymptomatic individuals (healthy blood donors).

Control andDisease groupsTotalnumberCCPointpositiveCCPointnegativeSpecificity
Blood donors456445299.1%
non-RA arthritis1870187100%
Psoriatic arthritis43043
IBD (CU/Crohn)1030103
Gout23023
CPPD707
Oligoarthritis707
Monoarthritis303
Palindrome arthritis101
Spondylarthropathy incl. AS21021100%
Systemic collagen disease126312397.6%
SLE/lupus like/UCTD64262
Sjögren's syndrome20119
PM/DM17017
MCTD15015
Systemic sclerosis10010
Vasculitis/PMR59059100%
PMR19019
Vasculitis (anti-MPO, anti-PR3)40040
Degenerative disease77077100%
Osteoarthritis77077
Pain syndrome/miscellaneous5715698.2%
FMS22022
Arthralgia/myalgia28127
Enthesopathy404
Low back pain303
Other non-RA autoimmunediseases49049100%
Thyroid disorder (anti-TPO)20020
Multiple Sclerosis20020
IDDM909
Infectious diseases108310597.2%
Epstein Barr Virus514
Parvovirus505
Mycoplasma909
Toxoplasma606
Tuberculosis303
Yersinia18018
Salmonella11110
Chlamydia514
Malaria303
Borrelia808
Syphilis505
Infectious endocarditis101
Legionella202
AST101
Schistomiasis101
Rubella404
Chagas syndrome101
Staphylococcus aureus10010
Helicobacter pylori10010
Routine samples (not RA)7927797.4%

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IBD (CU/Crohn) = Inflammatory bowel disease (colitis ulcerosa/Crohn's disease) CPPD = Calcium Pyrophosphate Deposition Disease = Ankylosing spondylitis AS = Systemic lupus erythematosus SLE UCTD = Unclassified connective tissue disease PM/DM = Polymyositis/Dermatomyositis MCTD = Mixed connective tissue disease PMR = Polymyalgia rheumatica = Anti-Myeloperoxidase Anti-MPO = Anti-Proteinase 3 Anti-PR3 FMS = Fibromyalgia syndrome Anti-TPO = Anti-Thyroid peroxidase IDDM = Insulin dependent diabetes mellitus AST = Anti-Streptolysine test

Clinical specificity

Healthy controls (blood donors)452/456 = 99.1%95% CI = 97.8 - 99.8%
non-RA arthritis187/187 = 100%95% CI = 98.0 - 100%
Spondylarthropathy incl. AS21/21 = 100%95% CI = 83.9 - 100%
Systemic collagen disease123/126 = 97.6%95% CI = 93.2 - 99.5%
Vasculitis/PMR59/59 = 100%95% CI = 93.9 - 100%
Degenerative disease77/77 = 100%95% CI = 95.3 - 100%
Pain syndrome/miscellaneous56/57 = 98.2%95% CI = 90.6 - 100%
Other non-rheumatic autoimmune diseases49/49 = 100%95% CI = 92.7 - 100%
Infectious diseases105/108 = 97.2%95% CI = 92.1 - 99.4%
Routine samples (not RA)77/79 = 97.4%95% CI = 91.2 - 99.7%

The 95% confidence interval (CI) was calculated using the exact method.

Accuracy

Inter-assay performance of the CCPoint® assay was evaluated using negative, low positive and high positive samples for antibodies against anti-CCP. Six different samples tested eight times each, by three different persons. All results obtained were 100% in agreement with the expected results.

Batch-to-batch performance of the CCPoint® assay was evaluated using negative, low positive and high positive samples for antibodies against anti-CCP. Six different samples tested eight times each, with three different batches. All results obtained were 100% in agreement with the expected results.

Interference study

One anti-CCP positive sample and one anti-CCP negative sample were spiked to the following concentrations in serum samples (and with its corresponding blank); Bilirubin F at 18.8 mg/dL, Bilirubin C at 20 mg/dL, Haemoglobin at 453 mg/dL, Chyle at 23.6 U/dL and Rheumatoid Factor (IgM) at 55 IU/mL. The data indicates that the assayed concentrations do not affect the accuracy of the test.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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 circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird-like figure with stylized wings and body.

Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993

Euro-Diagnostica AB c/o Robert Schiff, Ph.D., RAC, CQA(ASQ), President & CEO, Schiff & Company 1129 Bloomfield Avenue West Caldwell, NJ 07006

DEC 0 1 2010

Re: K093908

Trade Name: EuroDiagnostica CCPoint® Regulation Number: 21 CFR 866.5775 Regulation Name: Rheumatoid factor immunological test system Regulatory Class: Class II Product Code: NHX Dated: November 19, 2010 Received: November 22, 2010

Dear Dr. Schiff:

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 (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice

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· Page 2 - Robert Schiff, Ph.D., RAC, CQA(ASQ)

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 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 vours.

Henrik f. Sjö

for

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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DEC 1 2010

INDICATIONS FOR USE STATEMENT

510(k) Number (if known): Device Name:

K093908 CCPoint®

Indications for Use:

The Euro-Diagnostica CCPoint® test is a visually read, qualitative rapid lateral flow test for the detection of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human plasma or serum. The results of the test are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. For use by trained laboratory professionals. For in-vitro diagnostic use.

Prescription Use

Over-The-Counter Use

(Per 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 Device Evaluation and Safety (OIVD)

Rune Philip


Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510K K093908

§ 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).