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 C-reactive 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 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.

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.

AI/ML Overview

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based solely on the provided K050836 510(k) summary for the Sentinel CRP Diagnostic Assay:

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) summary provided does not explicitly state pre-defined acceptance criteria (e.g., a specific target for sensitivity, precision, or correlation coefficient). Instead, it relies on demonstrating substantial equivalence to predicate devices. The performance data presented is comparative, showing "equivalence" rather than meeting pre-set numerical thresholds.

However, based on the information provided, we can infer the performance aspects evaluated and summarize the reported findings:

Performance Aspect	Acceptance Criteria (Implied)	Reported Device Performance
Sensitivity	Comparable to predicate device.	Performance evaluation included sensitivity testing. (Specific numerical details not provided in summary).
Precision	Comparable to predicate device (intra-assay and inter-assay).	Performance evaluation included intra- and inter-assay precision testing. (Specific numerical details not provided in summary).
Prozone	Acceptable levels comparable to predicate device.	Performance evaluation included prozone testing. (Specific numerical details not provided in summary).
Interference	Acceptable levels comparable to predicate device.	Performance evaluation included interference testing. (Specific numerical details not provided in summary).
Method Comparison	Equivalence to predicate device across the measurement range.	"Equivalence was demonstrated across the total measurement range of 0.01 to 48.0 mg/dL" when compared to the Beckman Coulter IMMAGE Immunochemistry System CRP reagent. (Specific statistical measures like correlation coefficients or bias not provided in summary, but "equivalence" is claimed).
Analytical Range	Achieves expected analytical ranges as claimed.	Three measuring ranges achieved: Standard (0.02 – 32.0 mg/dL), Ultrasensitive (0.01 – 16.0 mg/dL), and Wide Range (0.02 – 48.0 mg/dL).

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

The 510(k) summary does not explicitly state the sample size used for the performance evaluations (sensitivity, precision, prozone, interference, and method comparison).

It also does not specify the data provenance (e.g., country of origin of the data, retrospective or prospective). Given that the submitter is from Italy (Sentinel CH Srl) and the contact person is also based in Rome, Italy, the studies might have been conducted in Italy or Europe, but this is not explicitly stated. The summary does not indicate whether the data was retrospective or prospective.

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

This information is not applicable in the context of this diagnostic assay submission. The "ground truth" for quantitative laboratory tests like CRP is typically established by reference methods or accepted clinical laboratory practices, not by expert consensus interpreting images or clinical cases. The comparison is done against existing, cleared diagnostic devices or reference standards.

4. Adjudication Method for the Test Set

This information is not applicable as the ground truth is not established through expert review requiring adjudication in this type of diagnostic assay. The comparison is a quantitative measurement against known values or an established predicate device.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed, nor would it typically be relevant for this type of in-vitro diagnostic device (IVD). MRMC studies are usually associated with diagnostic imaging devices or other tests that rely on human interpretation of complex data, where reader variability is a significant factor. The Sentinel CRP Diagnostic Assay is an automated immunoassay.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done

Yes, the device performance described (sensitivity, precision, prozone, interference, method comparison) represents standalone performance. The Sentinel CRP Vario is an automated immunoassay where human interaction is primarily for sample loading, initiating the test, and interpreting the numerical result from the automated analyzer. The "performance data" section explicitly discusses evaluations of the assay itself.

7. The Type of Ground Truth Used

The ground truth for evaluating the Sentinel CRP Diagnostic Assay consisted of:

Reference materials/standards: For evaluating sensitivity, precision, prozone, and interference, these would typically involve samples with known CRP concentrations (e.g., spiked samples, control materials).
Results from a predicate device: For the method comparison study ("comparison between the Sentinel CRP assay and the Beckman Coulter IMMAGE Immunochemistry System CRP reagent"), the results obtained from the predicate device (Beckman Coulter IMMAGE) served as a form of "ground truth" or reference for demonstrating equivalence.

8. The Sample Size for the Training Set

The 510(k) summary does not provide information regarding a "training set" sample size. This concept of a distinct training set is more common for machine learning or AI-based devices rather than traditional in-vitro diagnostic assays, which are typically developed and validated using a series of experiments with various samples.

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

As no training set is explicitly mentioned or relevant for this type of IVD in the provided summary, information on how its ground truth was established is not provided. The development of such assays involves established chemical and immunological principles, and calibration is performed using materials of known concentration (as described for the calibrator sets), rather than learning from a "training set" with established ground truth in the AI sense.

Summary

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

K Number: K050836

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

Tel.: +39 02 345514 1 Fax: +39 02 345514 64 e-mail: sentinel@sentinel.it

Maria E. Donawa, M.D. 2. Contact person: Donawa Consulting Srl Piazza Albania, 10 00153 Rome, Italy
Tel.: +39 06 578 2665 Fax: +39 06 574 3786 e-mail: medonawa@donawa.com
1. 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 orusual name	Trade orProprietary Name	Classificationname	Class	ProductCode	Classificationpanel
CRPdiagnosticassay	CRP Vario	C-reactive proteinimmunologicaltest system	II under 21 CFR866.5270	DKC	Immunology
CRPcalibrator	CRP Calibrator Set	CalibratorPrimary	II under 21 CFR862.1150	JIS	Immunology
CRPcalibrator	CRP Calibrator US	CalibratorPrimary	II under 21 CFR862.1151	JIS	Immunology
CRPcalibrator	CRP Calibrator WR	CalibratorPrimary	II under 21 CFR862.1152	JIS	Immunology
CRP control	CRP Control US	Quality ControlMaterial (assayedand unassayed)	I, reserved,under 21 CFR862.1660	JJY	ClinicalChemistry

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5. Device description

Application Method	Calibrators	Analytical Range
Standard Method	CRP Calibrator Set	0.02 – 32.0 mg/dL
Ultrasensitive Method	CRP Calibrator Set andCRP Calibrator US	0.01 – 16.0 mg/dL
Wide Range Method	CRP Calibrator Set andCRP Calibrator WR	0.02 – 48.0 mg/dL

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

6. Intended 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 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 DeviceTrade Name	Predicate DeviceName	Predicate DeviceManufacturer	Predicatedevice (K)	FDA clearancedate
6	CRP Vario	CRP-Latex (II)X2SEIKEN	Denka Seiken Co.	K030545	6 Feb. 2003
7	CRP Calibrator Set	CRP(II) Calibrators	Denka Seiken Co.	K030546	6 Feb. 2003
8	CRP Calibrator USused with CRPCalibrator Set	CRP(II) Calibrators	Denka Seiken Co.	K030546	6 Feb. 2003
9	CRP Calibrator WRused with CRPCalibrator Set	ImmageImmunochemistrySystem CRPreagent	Beckman Coulter,Inc.	K981638	6 Dec. 1998
10	CRP Control US	hsCRP ControlLevel 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 (240) 276-0484. 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 (800) 638-2041 or (301) 443-6597 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:

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:

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)

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

510(k) K050836

Page 1 of 1_________________________________________________________________________________________________________________________________________________________________

Regulation Number and Section

§ 866.5270 C-reactive protein immunological test system.

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