CRP DIAGNOSTIC ASSAY

K050836 · Sentinel Ch. Srl · DCK · Aug 8, 2005 · Immunology

Device Facts

• Record ID: K050836
• Device Name: CRP DIAGNOSTIC ASSAY
• Applicant: Sentinel Ch. Srl
• Product Code: DCK · Immunology
• Decision Date: Aug 8, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5270
• Device Class: Class 2

Intended Use

CRP Vario is an in vitro diagnostic test for the quantitative determination of C-reactive protein in human serum and lithium heparin or EDTA plasma samples by immunoturbidimetry. Measurement of C-reactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders. CRP Calibrators (CRP Calibrator Set, CRP Calibrator US and CRP Calibrator WR) are intended to be used for the calibration of the CRP Vario for the quantitative determination of Creactive protein in human serum and EDTA or lithium heparinized plasma samples. CRP Control US is intended for use as an assayed quality control material for serum C-reactive protein analysis.

Device Story

Sentinel CRP Vario is an in vitro diagnostic latex immunoassay for quantitative CRP determination in human serum/plasma. Human CRP antigens in sample bind to rabbit polyclonal anti-CRP antibodies on latex particles, causing agglutination. Automated chemistry analyzers detect agglutination via absorbance changes (550-580 nm). Magnitude of absorbance change is proportional to CRP concentration; concentration determined by interpolation from calibration curves using provided calibrators. Used in clinical laboratories by professional staff. Output assists clinicians in detecting/evaluating infection, tissue injury, and inflammatory disorders. System includes reagents, calibrators, and controls; requires specific analyzer settings (Methods) to achieve standard, ultrasensitive, or wide-range measuring intervals.

Clinical Evidence

Bench testing only. Performance validated via precision/reproducibility studies (within-run, run-to-run, total CVs reported), linearity (NCCLS EP6-A protocols), limit of quantitation (0.1-0.2 mg/L), and analytical specificity (interference testing for RF, bilirubin, hemoglobin, lipemia). Method comparison studies performed against commercially available nephelometric and turbidimetric methods (n=45-59 per method) showed high correlation (r=0.9988-0.9999). No clinical studies performed.

Technological Characteristics

Latex-enhanced immunoturbidimetric assay. Reagents: anti-CRP antibody-coated latex particles. Energy source: automated chemistry analyzer spectrophotometry (572 nm). Connectivity: integrated into Abbott Aeroset/Architect systems. Calibration: spline-based. Analytical ranges: 0.1-160 mg/L (High Sensitivity), 0.2-320 mg/L (Standard), 0.2-480 mg/L (Wide Range).

Indications for Use

Indicated for quantitative determination of C-reactive protein in human serum, lithium heparin, or EDTA plasma to aid in detection and evaluation of infection, tissue injury, and inflammatory disorders.

Regulatory Classification

Identification

A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.

Predicate Devices

• DENKA SEIKEN, CRP Latex (II)x2 Assay (k030545)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the words "SENTINEL DIAGNOSTICS" and the date "AUG 8 - 2005". The words "SENTINEL DIAGNOSTICS" are written in a stylized font, with the letters appearing to be made of individual lines. The date "AUG 8 - 2005" is written in a more standard font and is located above the word "SENTINEL".

### 510k Summary Sentinel C-Reactive Protein (CRP) Diagnostic Assay

K Number: K050836

1. Submitter's information: Mr. Ugo De Luca Managing Director Sentinel CH Srl Via Principe Eugenio 20155 Milan, Italy

> Tel.: [phone] Fax: [phone] e-mail: [e-mail]

- Maria E. Donawa, M.D. 2. Contact person: Donawa Consulting Srl Piazza Albania, 10 00153 Rome, Italy
Tel.: [phone] Fax: [phone] e-mail: [e-mail]

- 3. Date summary prepared: 31 March 2005
### 4. Device name and classification

The CRP Diagnostic Assay described in this 510(k) consists of reagents, calibrators and a control. packaged and distributed in five kits, but together making up the CRP assay. The device is intended to be sold as an in-vitro test for professional use.

Product name and classification information are provided in Table 4.1 below.

| Table 4.1 Device names and classification of Sentinel CRP DIAGNOSTIC ASSAY | | | | | |
|-----------------------------------------------------------------------------------|--|--|--|--|--|
| components | | | | | |
| | | | | | |

| Common or<br>usual name | Trade or<br>Proprietary Name | Classification<br>name | Class | Product<br>Code | Classification<br>panel |
|----------------------------|------------------------------|--------------------------------------------------------|------------------------------------------|-----------------|-------------------------|
| CRP<br>diagnostic<br>assay | CRP Vario | C-reactive protein<br>immunological<br>test system | II under 21 CFR<br>866.5270 | DKC | Immunology |
| CRP<br>calibrator | CRP Calibrator Set | Calibrator<br>Primary | II under 21 CFR<br>862.1150 | JIS | Immunology |
| CRP<br>calibrator | CRP Calibrator US | Calibrator<br>Primary | II under 21 CFR<br>862.1151 | JIS | Immunology |
| CRP<br>calibrator | CRP Calibrator WR | Calibrator<br>Primary | II under 21 CFR<br>862.1152 | JIS | Immunology |
| CRP control | CRP Control US | Quality Control<br>Material (assayed<br>and unassayed) | I, reserved,<br>under 21 CFR<br>862.1660 | JJY | Clinical<br>Chemistry |

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Image /page/1/Picture/0 description: The image shows the logo for Sentinel Diagnostics. The word "SENTINEL" is written in large, bold, stylized letters. Below it, in smaller letters, is the word "DIAGNOSTICS".

#### 5. Device description

The Sentinel CRP Vario kit is a latex in vitro diagnostic immunoassay for the quantitative determination of C-reactive protein (CRP) in human serum and in heparinized and EDTAplasma. Human CRP antigens in the sample bind to the specific anti-CRP antibody absorbed to latex particles, and agglutination occurs. This agglutination is detected as an absorbance change when read on an automated chemistry analyzer at wavelengths between 550 - 580 nm. The magnitude of the change in absorbance is proportional to the quantity of CRP in the sample. The actual concentration is then determined by interpolation from a calibration curve prepared from calibrators of known concentration using the CRP Calibrator Set, CRP Calibrator US, or CRP Calibrator WR.

The Sentinel CRP Calibrator Set, CRP Calibrator US and CRP Calibrator WR are prepared by diluting purified CRP with normal human serum to reach CRP concentrations of 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 16.0, 32.0 and 48.0 mg/dL.

By using the CRP Vario with the Sentinel calibrator kits, each used with specific analyzer settings called Methods, three measuring ranges can be achieved. The combinations of calibrators, method used and analytical ranges are listed in Table 5.1.

| Application Method | Calibrators | Analytical Range |
|-----------------------|---------------------------------------------|-------------------|
| Standard Method | CRP Calibrator Set | 0.02 – 32.0 mg/dL |
| Ultrasensitive Method | CRP Calibrator Set and<br>CRP Calibrator US | 0.01 – 16.0 mg/dL |
| Wide Range Method | CRP Calibrator Set and<br>CRP Calibrator WR | 0.02 – 48.0 mg/dL |

Table 5.1 Method, calibrators, and analytical ranges for CRP Vario

The Standard and the Wide Range Methods can be used with any available commercial quality control materials. The CRP Vario with the Ultrasensitive Method requires a Sentinel control, CRP Control US, for the approximate CRP concentration of 0.05 mg/dL to ensure the effectiveness of CRP measurements at very low CRP concentrations.

#### 6. Intended Use

CRP Vario is an in vitro diagnostic test for the quantitative determination of C-reactive protein in human serum and lithium heparin or EDTA plasma samples by immunoturbidimetry. Measurement of C-reactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders.

CRP Calibrators (CRP Calibrator Set, CRP Calibrator US and CRP Calibrator WR) are intended to be used for the calibration of the CRP Vario for the quantitative determination of Creactive protein in human serum and EDTA or lithium heparinized plasma samples.

CRP Control US is intended for use as an assayed quality control material for serum C-reactive protein analysis.

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#### 7. Comparison with Predicate Devices

Table 7.1 below provides a list of predicate devices for the Sentinel CRP Diagnostic Assay devices.

| | | | | | Table 7.1 Predicate devices for Sentinel CRP DIAGNOSTIC ASSAY devices | | |
|--|--|--|--|--|-----------------------------------------------------------------------|--|--|
|--|--|--|--|--|-----------------------------------------------------------------------|--|--|

| | Sentinel Device<br>Trade Name | Predicate Device<br>Name | Predicate Device<br>Manufacturer | Predicate<br>device (K) | FDA clearance<br>date |
|----|------------------------------------------------------|----------------------------------------------------|----------------------------------|-------------------------|-----------------------|
| 6 | CRP Vario | CRP-Latex (II)X2<br>SEIKEN | Denka Seiken Co. | k030545 | 6 Feb. 2003 |
| 7 | CRP Calibrator Set | CRP(II) Calibrators | Denka Seiken Co. | k030546 | 6 Feb. 2003 |
| 8 | CRP Calibrator US<br>used with CRP<br>Calibrator Set | CRP(II) Calibrators | Denka Seiken Co. | k030546 | 6 Feb. 2003 |
| 9 | CRP Calibrator WR<br>used with CRP<br>Calibrator Set | Immage<br>Immunochemistry<br>System CRP<br>reagent | Beckman Coulter,<br>Inc. | k981638 | 6 Dec. 1998 |
| 10 | CRP Control US | hsCRP Control<br>Level 1 | CLINIQA | k011169 | 18 May 2001 |

The Sentinel's CRP reagents, calibrators and control and the predicate devices are both used for the determination of C-Reactive protein. In addition, they use the same::

- Sample type: human serum and plasma .
- Technology: latex particle agglutination .
- Antibody: rabbit polyclonal .
- Detection method: agglutination measurement .
- Calibration: against multipoint calibrators. .

However, CRP Vario must be used with the Abbott AEROSET® and ARCHITECT® analyzers, whereas the Denka Seiken CRP-Latex (II)X2 Assay Kit labeling indicates that the product can be used with any automated clinical chemistry analyzer.

#### 8. Performance Data

Performance evaluations included sensitivity, intra- and inter-assay precision, prozone and interference testing. In addition, Sentinel performed comparisons between the Sentinel CRP assay and the Beckman Coulter IMMAGE Immunochemistry System CRP reagent. Equivalence was demonstrated across the total measurement range of0.01 to 48.0 mg/dL.

#### 9. Conclusion

The performance and safety data presented in this premarket notification support a finding of substantial equivalence between the Sentinel CRP Diagnostic Assay and the predicate devices specified in this submission.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/3/Picture/2 description: The image is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized graphic of three human profiles facing right, stacked on top of each other. The profiles are rendered in a thick, black line, giving them a bold and distinct appearance.

AUG 8 - 2005

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Sentinel CH Srl c/o Maria E. Donawa, M.D. Donawa Consulting Srl Piazza Albania, 10 00153 Rome, Italy

Re: k050836

Trade/Device Name: CRP Calibrators (including CRP Calbrator Set, CRP Calibrator US and CRP Calibrator WR) CRP Vario CRP Control US Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCK, JIS, JJY Dated: June 23, 2005 Received: July 6, 2005

Dear Dr. Donawa:

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 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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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 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 [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Carol C. Benam

Carol C. Benson, M.A. Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number: K 050836

CRP Calibrators (including CRP Calibrator Set, CRP Calibrator US and CRP Device Name: Calibrator WR)

Indications for Use:

CRP Calibrators (CRP Calibrator Set, CRP Calibrator US and CRP Calibrator WR) are intended to be used for the calibration of the CRP Vario for the quantitative determination of C-reactive protein in human serum and EDTA or lithium heparinized plasma samples.

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 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)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) k050836

Page 1 of ____________________________________________________________________________________________________________________________________________________________________

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## Indications for Use

510(k) Number: K050836

CRP Vario Device Name:

Indications for Use:

CRP Vario is an in vitro diagnostic test for the quantitative determination of C-reactive protein in human serum and lithium heparin or EDTA plasma samples by immunoturbidimetry. Measurement of C-reactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 801 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)

signature

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

5100 k050836

Page 1 of ____________________________________________________________________________________________________________________________________________________________________

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# Indications for Use

150136 K 510(k) Number:

CRP Control US Device Name:

Indications for Use:

CRP Control US is intended for use as an assayed quality control material for serum C-reactive protein analysis.

Prescription Use × (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use _ (21 CFR 801 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)

AC

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

510(k) K050836

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