CCPOINT

K093908 · Euro-Diagnostica AB · NHX · Dec 1, 2010 · Immunology

Device Facts

• Record ID: K093908
• Device Name: CCPOINT
• Applicant: Euro-Diagnostica AB
• Product Code: NHX · Immunology
• Decision Date: Dec 1, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5775
• Device Class: Class 2

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 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.

Device Story

CCPoint® is a qualitative, visually read lateral flow immunoassay for detecting anti-CCP IgG antibodies in human serum or plasma. The device utilizes a porous membrane with immobilized synthetic cyclic citrullinated peptides in the test zone and colloidal gold-conjugated anti-human IgG in the conjugate pad. Operation involves adding a sample to the port, followed by a running buffer that mobilizes the gold conjugate. Capillary action moves the sample and conjugate across the membrane; anti-CCP antibodies bind to the peptide-antigens, forming a visible red line in the test zone. A control line confirms reagent activity. Used in clinical laboratory settings by trained professionals, the test provides qualitative results to assist clinicians in diagnosing Rheumatoid Arthritis alongside other clinical and laboratory findings.

Clinical Evidence

Performance evaluated using 1062 retrospective sera (606 RA, 456 healthy donors) compared to the predicate ELISA. Results showed 99.6% positive percent agreement, 99.4% negative percent agreement, and 99.4% overall agreement. Clinical sensitivity for RA was 73.5% (438/596). Specificity was evaluated across various disease groups (non-RA arthritis, systemic collagen disease, infectious diseases, etc.), ranging from 97.2% to 100%. Inter-assay and batch-to-batch precision studies showed 100% agreement. Interference studies confirmed no impact from bilirubin, hemoglobin, chyle, or rheumatoid factor.

Technological Characteristics

Lateral flow immunoassay; colloidal gold-based detection; porous membrane with immobilized synthetic CCP; anti-human IgG conjugate; visual readout; qualitative; serum/plasma matrix; undiluted sample; manual operation.

Indications for Use

Indicated for use as an aid in the diagnosis of Rheumatoid Arthritis (RA) in patients suspected of having the disease. For use by trained laboratory professionals using human serum or plasma.

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

• Immunoscan RA anti-CCP test kit (K052133)

Submission Summary (Full Text)

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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: [phone] Fax: [phone] 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

| ltem | Device | Predicate Device |
|------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | CCPoint® | Immunoscan RA<br>anti-CCP |
| Intended use | The results of the test are<br>to be used as an aid to the<br>diagnosis of Rheumatoid<br>Arthritis (RA), in<br>conjunction with other<br>laboratory and clinical<br>findings. | The results of the assay<br>are to be used as an aid<br>to the diagnosis of<br>Rheumatoid Arthritis<br>(RA), in conjunction<br>with other laboratory<br>and clinical findings. |
| Intended user | For use by trained<br>laboratory professionals | For use by health care<br>professionals |
| Type of test | Qualitative | Qualitative and semi-<br>quantitative |
| Analyte measured | Anti-CCP | Anti-CCP |
| Coated antigen | Synthetic CCP | Synthetic CCP |
| Conjugate | Anti-human IgG | Anti-human IgG |

# Differences

| Item | Device | Predicate Device |
|----------------------|------------------|---------------------------------------|
| | CCPoint® | Immunoscan RA<br>anti-CCP |
| Method | Lateral flow | ELISA |
| Test matrix | Serum and plasma | Serum |
| Type of test | Qualitative | Qualitative and semi-<br>quantitative |
| Sample dilution | Undiluted | Diluted 1:50 |
| Measuring of results | Visually read | ELISA 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<br>(Immunoscan RA anti-CCP) | |
|-----------------------------|-------------------|----------------------------------------------|----------|
| New device | N = 1052 | Positive | Negative |
| CCPoint® | Positive | 444 | 4 |
| | Negative | 2 | 612 |
| 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<br>(Immunoscan RA anti-CCP) | |
|-----------------------------|-----------------|----------------------------------------------|----------|
| New device | N = 399 | Positive | Negative |
| CCPoint® | Positive | 377 | 4 |
| | Negative | 2 | 16 |
| 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.

| | n | negative | positive | Sensitivity |
|----------------------------------------|-----|----------|----------|-------------|
| Patients with clinically<br>defined RA | 596 | 158 | 438 | 73.5% |

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 and<br>Disease groups | Total<br>number | CCPoint<br>positive | CCPoint<br>negative | Specificity |
|-------------------------------------|-----------------|---------------------|---------------------|-------------|
| Blood donors | 456 | 4 | 452 | 99.1% |
| non-RA arthritis | 187 | 0 | 187 | 100% |
| Psoriatic arthritis | 43 | 0 | 43 | |
| IBD (CU/Crohn) | 103 | 0 | 103 | |
| Gout | 23 | 0 | 23 | |
| CPPD | 7 | 0 | 7 | |
| Oligoarthritis | 7 | 0 | 7 | |
| Monoarthritis | 3 | 0 | 3 | |
| Palindrome arthritis | 1 | 0 | 1 | |
| Spondylarthropathy incl. AS | 21 | 0 | 21 | 100% |
| Systemic collagen disease | 126 | 3 | 123 | 97.6% |
| SLE/lupus like/UCTD | 64 | 2 | 62 | |
| Sjögren's syndrome | 20 | 1 | 19 | |
| PM/DM | 17 | 0 | 17 | |
| MCTD | 15 | 0 | 15 | |
| Systemic sclerosis | 10 | 0 | 10 | |
| Vasculitis/PMR | 59 | 0 | 59 | 100% |
| PMR | 19 | 0 | 19 | |
| Vasculitis (anti-MPO, anti-PR3) | 40 | 0 | 40 | |
| Degenerative disease | 77 | 0 | 77 | 100% |
| Osteoarthritis | 77 | 0 | 77 | |
| Pain syndrome/miscellaneous | 57 | 1 | 56 | 98.2% |
| FMS | 22 | 0 | 22 | |
| Arthralgia/myalgia | 28 | 1 | 27 | |
| Enthesopathy | 4 | 0 | 4 | |
| Low back pain | 3 | 0 | 3 | |
| Other non-RA autoimmune<br>diseases | 49 | 0 | 49 | 100% |
| Thyroid disorder (anti-TPO) | 20 | 0 | 20 | |
| Multiple Sclerosis | 20 | 0 | 20 | |
| IDDM | 9 | 0 | 9 | |
| Infectious diseases | 108 | 3 | 105 | 97.2% |
| Epstein Barr Virus | 5 | 1 | 4 | |
| Parvovirus | 5 | 0 | 5 | |
| Mycoplasma | 9 | 0 | 9 | |
| Toxoplasma | 6 | 0 | 6 | |
| Tuberculosis | 3 | 0 | 3 | |
| Yersinia | 18 | 0 | 18 | |
| Salmonella | 11 | 1 | 10 | |
| Chlamydia | 5 | 1 | 4 | |
| Malaria | 3 | 0 | 3 | |
| Borrelia | 8 | 0 | 8 | |
| Syphilis | 5 | 0 | 5 | |
| Infectious endocarditis | 1 | 0 | 1 | |
| Legionella | 2 | 0 | 2 | |
| AST | 1 | 0 | 1 | |
| Schistomiasis | 1 | 0 | 1 | |
| Rubella | 4 | 0 | 4 | |
| Chagas syndrome | 1 | 0 | 1 | |
| Staphylococcus aureus | 10 | 0 | 10 | |
| Helicobacter pylori | 10 | 0 | 10 | |
| Routine samples (not RA) | 79 | 2 | 77 | 97.4% |

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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 arthritis | 187/187 = 100% | 95% CI = 98.0 - 100% |
| Spondylarthropathy incl. AS | 21/21 = 100% | 95% CI = 83.9 - 100% |
| Systemic collagen disease | 123/126 = 97.6% | 95% CI = 93.2 - 99.5% |
| Vasculitis/PMR | 59/59 = 100% | 95% CI = 93.9 - 100% |
| Degenerative disease | 77/77 = 100% | 95% CI = 95.3 - 100% |
| Pain syndrome/miscellaneous | 56/57 = 98.2% | 95% CI = 90.6 - 100% |
| Other non-rheumatic autoimmune diseases | 49/49 = 100% | 95% CI = 92.7 - 100% |
| Infectious diseases | 105/108 = 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 [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 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)

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

Rune Philip

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Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510K k093908