The CRP Vario assay [CRPVa] is for in vitro diagnostic use in the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma (sodium and lithium heparin) using the ARCHITECT c Systems. Measurement of C-reactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders.

CRP Calibrators (including CRP Calibrator Set, CRP Calibrator HS 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 or plasma samples.

Device Description

The CRP Vario assay is intended for the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma. It is supplied as a two-reagent kit. The kit contains Reagent 1 (Glycine buffer) and Reagent 2 (Anti-CRP polyclonal antibodies adsorbed on latex particles). Two different sizes of the product are available. The submission also describes CRP Calibrators (CRP Calibrator Set, CRP Calibrator HS, and CRP Calibrator WR) which are prepared by diluting CRP with human serum and stabilized by adding sodium azide.

AI/ML Overview

Here's an analysis of the acceptance criteria and study as described in the provided document:

Acceptance Criteria and Device Performance for CRP Vario

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document explicitly refers to an "Acceptance Criteria" column for Method Comparison in Table 15-3. For other performance characteristics, the "acceptance criteria" can be inferred by comparing the candidate device's stated performance to that of the predicate device, or by general statements about meeting recommendations or consistency with original submissions.

Feature	Acceptance Criteria	Reported Device Performance (Candidate Device CRP Vario)	Met?
Method Comparison
High Sensitivity Method (Slope)	0.95 – 1.05	0.969 (0.964 – 0.974)	Yes
High Sensitivity Method (R)	≥ 0.975	1.000	Yes
High Sensitivity Method (n)	≥ 100	111	Yes
Standard Method (Slope)	0.95 – 1.05	0.956 (0.925 – 0.997)	Yes
Standard Method (R)	≥ 0.975	1.000	Yes
Standard Method (n)	≥ 100	119	Yes
Wide Range Method (Slope)	0.95 – 1.05	0.976 (0.944 – 0.993)	Yes
Wide Range Method (R)	≥ 0.975	1.000	Yes
Wide Range Method (n)	≥ 100	119	Yes
Limit of Quantitation (LoQ)
LOQ for hsCRP	≤ 0.03 mg/dL	"The LOQ results are consistent with the original submission." (Original submission stated 0.01 mg/dL for High Sensitivity Method, which is the hsCRP method).	Yes
LOQ for Standard and Wide Range Methods	≤ 0.05 mg/dL	"The LOQ results are consistent with the original submission." (Original submission stated 0.02 mg/dL for Standard and Wide Range Methods).	Yes
Linearity
High Sensitivity Method	Meets pre-specified allowable error criteria against 2nd and 3rd order polynomial fits.	Found to extend up to 16.00 mg/dL.	Yes
Standard Method	Meets pre-specified allowable error criteria against 2nd and 3rd order polynomial fits.	Found to extend up to 32.00 mg/dL.	Yes
Wide Range Method	Meets pre-specified allowable error criteria against 2nd and 3rd order polynomial fits.	Found to extend up to 48.00 mg/dL.	Yes

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

Method Comparison Test Set:
- High Sensitivity Method: N = 111 human serum samples
- Standard Method: N = 119 human serum samples
- Wide Range Method: N = 119 human serum samples
- Data Provenance: The document states "Human serum samples, spanning the measuring range, were tested." No information is provided regarding the country of origin or whether the data was retrospective or prospective.
Limit of Quantitation (LoQ) Test Set:
- The study used serum pools diluted with SeraSub (a synthetic serum) to create 8 low-level analyte samples (0.08, 0.06, 0.05, 0.04, 0.03, 0.02, 0.01, and 0.005 mg/dL).
- Each sample was tested in a minimum of 10 replicates per run, with 2 runs per day over 3 days, resulting in a total of 60 replicates per sample.
Linearity Test Set:
- A high CRP serum pool was mixed with a low serum pool to generate 12 concentrations.
- Each concentration level was tested in triplicate determinations.

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

This section is not applicable to this type of device and study. The CRP Vario is an in vitro diagnostic device that quantifies C-reactive protein. Its performance is evaluated against reference methods (e.g., predicate devices, established analytical protocols) and CLSI guidelines, not against expert human interpretations of images or clinical reports. There are no "experts" establishing a subjective ground truth in the way described for AI in image analysis.

4. Adjudication Method for the Test Set

This section is not applicable. As an in vitro diagnostic device, the performance is determined by quantitative measurements and statistical comparisons with reference methods, not by adjudication of interpretations by multiple human readers.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. This type of study evaluates human reader performance often in the context of imaging diagnostics. The CRP Vario is an in vitro diagnostic for laboratory analysis, not a device requiring human interpretation in this manner.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies reported here (Method Comparison, Linearity, Limit of Quantitation) are standalone performance evaluations of the CRP Vario assay. The device itself is an automated immunoturbidimetric system (ARCHITECT c8000 system) for quantitative measurement, operating without human interpretation of the final result, beyond standard laboratory quality control and result reporting.

7. The Type of Ground Truth Used

The "ground truth" for the performance evaluation of the CRP Vario was established by:

Reference Methods / Predicate Device: For the Method Comparison study, the candidate CRP Vario (traceable to ERM-DA472/IFCC) was compared against a Beckman Coulter CRP Latex REF. OSR6199 (traceable to CRM 470) on an AU5800 platform.
CLSI Guidelines: Formal CLSI (Clinical and Laboratory Standards Institute) protocols (EP09-A3 for Method Comparison, EP06-A for Linearity, EP17-A2 for LoQ) were followed, indicating that the acceptable statistical and analytical measures defined by these standards served as the basis for evaluating performance.
Dilution Series / Known Concentrations: For Linearity and LoQ, the "ground truth" was derived from precisely prepared serum pools and their serial dilutions to known or targeted concentrations.

8. The Sample Size for the Training Set

This section is not applicable. The CRP Vario is a re-submission for a modification of an existing in vitro diagnostic device, not an AI/ML device that requires a distinct "training set" in the computational sense. Its performance is characterized through analytical verification and validation studies.

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

This section is not applicable for the reasons stated in point 8.

Summary

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November 8, 2019

Sentinel CH, Spa Patricia Dupe Head of Quality System Via Robert Koch, 2 Milano, 20152 It

Re: K192118

Trade/Device Name: CRP Vario Regulation Number: 21 CFR 866.5270 Regulation Name: C-Reactive Protein Immunological Test System Regulatory Class: Class II Product Code: DCK Dated: August 1, 2019 Received: August 6, 2019

Dear Patricia Dupe:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Douglas Jeffery, Ph.D. Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2020 See PRA Statement below.

510(k) Number (if known) K192118

Device Name CRP Vario

Indications for Use (Describe)

CRP Vario

CRP Calibrators (including CRP Calibrator Set, CRP Calibrator HS and CRP Calibrator WR): CRP Calibrators are intended to be used for the CRP Vario for the quantitative determination of C reactive protein in human serum or plasma samples.

Type of Use (Select one or both, as applicable)
-------------------------------------------------

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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Section 15: 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807,92.

In accordance with 21 CFR 807.87, SENTINEL CH. hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification Special 510(k).

The purpose of this Special 510(k) Premarket Notification is to inform FDA of the proposed modifications to the CRP Vario labeling and provide sufficient detail to support a determination of substantial equivalence.

The primary change in the candidate device, CRP Vario, from the predicated device is the modification in the traceability of the assay from CRM 470 to ERM-DA472/IFCC.

Other changes that will also be addressed are the removal of the EDTA as tube type used for the specimen storage and the revision of the specimen from 3 years to 1 year when stored at -20°C.

Moreover, other changes to the device labeling implemented since the product initially cleared in 2005 were evaluated per the FDA Guidance document "Deciding When to Submit a 510(k)". Per the quidance document these changes required documentation only, and they did not present any new risks. The labeling changes are listed below:

revision of the interference data for Bilirubin which was also separated into ● Conjugated and Unconjugated Bilirubin
. revision of the High Sensitivity method precision

Note: There were no prior submissions for this device for which FDA provided feedback related to the data or information needed to support substantial equivalence.

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Submitter Name	SENTINEL CH. SpA
Address	Via Robert Koch,2Milano (MI)20152, Italy
Contact	Primary:Patricia Dupé+39 02 345 514 496+39 02 345 514 64patriciadupe@sentinel.it
Date prepared	November 08, 2019
Proprietary Name	CRP Vario
Common name	C-Reactive Protein, Antigen, Antiserum, and Control
Classification Name	C-Reactive Protein, Antigen, Antiserum, and ControlDevice, (21CFR 866.5270, Class 2 device)
Product Code	DCK
Predicate Devices	The candidate device is a modification of the predicatedevice. The device name, CRP Vario, is unchanged fromhow it was cleared in 510(k) K050836 on August 8th, 2005and CLIA categorized on October 1st,2008
EstablishmentRegistration	The Establishment Registration number for SENTINEL CH.SpA is 9681753

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1. DEVICE DESCRIPTION

The CRP Vario assay is intended for the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma.

It is supplied as a two-reagent kit which contains 2 reagents composed as follow:

Reactive Ingredients	Concentration
Reagent 1: Glycine buffer (pH 7.0)	1.28%
Reagent 2: Anti-CRP polyclonal antibodies(rabbit) adsorbed on latex particles	0.2%

Inactive Ingredients:

Reagent 1: contains bovine albumin (≤ 1%) and sodium azide (< 0.1%). Reagent 2: contains bovine albumin (≤ 0.1%) and sodium azide (<0.1%).

Two different sizes of the product are available:

REF	6K26-30	6K26-41
Reagent 1	2 x 37 mL	3 x 86 mL
Reagent 2	2 x 37 mL	3 x 86 mL

A description of the CRP Calibrators, cleared under the same 510(k) K050836, are reported below:

1. CRP Calibrator Set

CRP Calibrator Set contains the following calibrator levels and it is prepared by diluting CRP with human serum and stabilized by adding sodium azide (< 0.1%).

The values assigned and the color of the caps corresponding to each level are indicated in the table below.

Contents of Kit	Short Name	Cap Color	Concentration mg/dL	Concentration mg/L	Quantity
Calibrator	CRP05	White	0.50	5.0	1 x 2 mL
Calibrator	CRP10	Light yellow	1.00	10.0	1 x 2 mL
Calibrator	CRP20	Light green	2.00	20.0	1 x 2 mL
Calibrator	CRP40	Light blue	4.00	40.0	1 x 2 mL
Calibrator	CRP80	Pink	8.00	80.0	1 x 2 mL
Calibrator	CRP160	Magenta	16.00	160.0	1 x 2 mL
Calibrator	CRP320	Brown	32.00	320.0	1 x 2 mL

To convert results from mg/dL to mg/L, multiply by 10.

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2. CRP Calibrator HS

CRP Calibrator HS contains the following calibrator level and it is prepared by diluting CRP with human serum and stabilized by adding sodium azide (< 0.1%).

The value assigned and the color of the cap are indicated in the table below.

Contents ofKit	ShortName	CapColor	Concentrationmg/dL	Concentrationmg/L	Quantity
Calibrator	CRPHS	yellow	0.25	2.50	1 x 2 mL

To convert results from mg/dL to mg/L, multiply by 10.

3. CRP Calibrator WR

CRP Calibrator WR contains the following calibrator level and it is prepared by diluting CRP with human serum and stabilized by adding sodium azide (< 0.1%).

The value assigned and the color of the cap are indicated in the table below.

Contents ofKit	ShortName	CapColor	Concentrationmg/dL	Concentrationmg/L	Quantity
Calibrator	CRPWR	Green	48.00	480.000	1 x 2 mL

To convert results from mg/dL to mg/L, multiply by 10.

2. INDICATIONS FOR USE

The CRP Vario assay [CRPVa] is for in vitro diagnostic use in the quantitative immunoturbidimetric determination of C-reactive protein in human serum and plasma (sodium and lithium heparin) using the ARCHITECT c Systems. Measurement of Creactive protein is useful in the detection and evaluation of infection, tissue injury and inflammatory disorders.

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3. TECHNOLOGICAL CHARACTERISTICS

The primary change in the candidate device, CRP Vario, from the predicated device is the modification in the traceability of the assay from CRM 470 to ERM-DA472/IFCC.

Other changes that will also be addressed are the removal of the EDTA as tube type used for the specimen storage and the revision of the stability of the specimen from 3 years to 1 year when stored at -20°C.

Moreover, other changes to the device labeling implemented since the product initially cleared in 2005 were evaluated per the FDA Guidance document "Deciding When to Submit a 510(k)". Per the guidance document these changes required documentation only, and they did not present any new risks. The labeling changes are listed below:

revision of the interference data for Bilirubin which was also separated into . Conjugated and Unconjugated Bilirubin
. revision of the High Sensitivity method precision

The following Table 15-1 and Table 15-2 compare the CRP Vario with its predicate device, CRP Vario (K050836).

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Table 15-1: Assay Comparison, General Assay Features

Feature	Predicate Device CRP Vario (K050836)	Candidate Device CRP Vario
ReagentFormulation	Reactive Ingredient Reagent 1: Glycinebuffer (pH 7.0) (1.28%)Reactive Ingredient Reagent 2: Anti-CRP polyclonal antibodies (rabbit)adsorbed on latex particles (0.2%)	Same
Classification	Regulation name: C-Reactive Protein,Antigen, Antiserum, and Control Device	Same
Test principle	Turbidimetric / Immunoturbidimetric	Same
Intended Use	The CRP Vario assay is used for thequantitative immunoturbidimetricdetermination of C-reactive protein inhuman serum and plasma with variableassay ranges [CRP16, CRP32, CRP48]using the ARCHITECT c 8000® System,the ARCHITECT c 16000™ System, andthe AEROSET System.	The CRP Vario assay [CRPVa] is for invitro diagnostic use in the quantitativeimmunoturbidimetric determination ofC-reactive protein in human serum andplasma (sodium and lithium heparin)using the ARCHITECT c Systems.Measurement of C-reactive protein isuseful in the detection and evaluationof infection, tissue injury andinflammatory disorders.
Specimen Type	Human serum, plasma	Same
Specimen tube type	· Serum· Plasma with the following acceptableanticoagulants:lithium heparin (with orwithout gel barrier), sodium heparin, andEDTA	· Serum· Plasma with the following acceptableanticoagulants: lithium heparin (with orwithout gel barrier) and sodium heparin
Specimen storage	TemperatureStorage Maximum 20 to 25°C 15 days 2 to 8°C 2 months -20°C 3 years		TemperatureStorage Maximum 20 to 25°C 15 days 2 to 8°C 2 months -20°C 1 year
Standardization ofthe calibrator	This method has been standardizedagainst CRM 470	This method has been standardizedagainst ERM-DA472/IFCC

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Table 15-2: Assay Comparison, Labeled Performance Characteristics

Feature	Predicate Device CRP Vario (K050836)	Candidate Device CRP Vario
Measuringrange	High Sensitivity Method 0.01 to 16.00 mg/dL (0.1 to 160 mg/L) Standard Method 0.02 to 32.00 mg/dL (0.2 to 320 mg/L) Wide Range 0.02 to 48.00 mg/dL (0.2 to 480 mg/L)	Same
Limit ofQuantitation	High Sensitivity Method 0.01 mg/dL (0.1 mg/L) Standard and Wide Range Methods 0.02 mg/dL (0.2 mg/L)	Same
Referencerange	Serum and plasma: ≤ 5 mg/L (0.5 mg/dL)	Same
AnalyticalSpecificity	The CRP Vario test is not affected by the presence of: Rheumatoid Factor up to 550 IU/MI conjugated and fetal bilirubin up to 30 mg/dL hemoglobin up to 0.5 g/dL and lipemia (< 5% intra-lipid approximating 1500 mg/dL of triglycerides).	Intereferingsubstance InterferentConcentration Bilirubin, conjugated 66 mg/dL (1129 μmol/L) Bilirubin, cunonjugated 66 mg/dL (1129 μmol/L) Hemoglobin 500 mg/dL (5 g/L) Intralipid 1,500 mg/dL (15 g/L) Rheumatoid Factor 550 IU/MI (550 kU/L)
Precision	CRP High Sensitivity Method Level 1 Level 2 Level 3 Level 4 N 40 40 40 40 Mean (mg/L) 0.462 4.92 11.35 45.88 Within Run SD 0.019 0.035 0.148 0.298 %CV 4.00 0.72 1.30 0.65 Between Run SD 0.011 0.024 0.109 0.120 %CV 2.38 0.49 0.96 0.26 Total SD 0.022 0.043 0.183 0.389 %CV 4.66 0.87 1.62 0.85 NOTE: %CV was calculated prior to rounding Mean and SD.CRP Standard Method Level 1 Level 2 Level 3 Level 4 N 40 40 40 40 Mean (mg/L) 5.10 18.30 73.30 319.40 Within Run SD 0.10 0.11 0.37 2.08 %CV 1.97 0.59 0.50 0.65 Between Run SD 0.04 0.12 0.14 1.12 %CV 0.78 0.65 0.19 0.35 Total SD 0.11 0.19 0.40 2.70 %CV 2.15 1.04 0.54 0.85 NOTE: %CV was calculated prior to rounding Mean and SD.CRP Wide Range Method Level 1 Level 2 Level 3 Level 4 N 40 40 40 40 Mean (mg/L) 5.20 18.40 90.20 268.00 Within Run SD 0.06 0.18 0.69 3.32 %CV 1.16 0.99 0.77 1.24 Between Run SD 0.05 0.08 0.76 3.35 %CV 0.98 0.44 0.84 1.25 Total SD 0.1 0.22 1.25 4.92 %CV 1.91 1.17 1.39 1.83

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Feature	Predicate Device CRP Vario (K050836)		Candidate Device CRP Vario
Methodcomparison	CRP High Sensitivity MethodNY - Intercept (95% CI)Correlation CoefficientSlope (95% CI)Standard Error of the EstimateRange (mg/L)* CI = Confidence Interval	AEROSET vs.Nephelometer45-0.24 to 0.540.99940.985 to 1.0060.961.0 to 104.0	ARCHITECT vs.AEROSET45-0.33 to 0.450.99940.975 to 0.9960.961.1 to 103.3	Same
	CRP High Sensitivity Method(continued)NY - Intercept (95% CI)Correlation CoefficientSlope (95% CI)Standard Error of the EstimateRange (mg/L)* CI = Confidence Interval	AEROSET vs.TurbidimetricMethod55-0.01 to 0.070.99950.992 to 1.0090.100.2 to 13.6	ARCHITECT vs.TurbidimetricMethod55-0.02 to 0.100.99901.001 to 1.0350.140.2 to 13.6
	CRP Standard MethodNY - Intercept (95% CI)Correlation CoefficientSlope (95% CI)Standard Error of the EstimateRange (mg/L)* CI = Confidence Interval	AEROSET vs.Nephelometer54-0.68 to 0.500.99961.004 to 1.0201.641.0 to 219.0	ARCHITECT vs.AEROSET54-0.64 to 0.460.99970.977 to 0.9911.580.6 to 223
	CRP Wide Range MethodNY - Intercept (95% CI)Correlation CoefficientSlope (95% CI)Standard Error of the EstimateRange (mg/L)* Cl = Confidence Interval	AEROSET vs.Nephelometer59-1.26 to 1.530.99891.023 to 1.0514.101.0 to 286.0	ARCHITECT vs.AEROSET59-1.44 to 2.040.99820.968 to 0.9995.280.7 to 301.2
Shelf Life	The shelf life for the CRP Vario is 18 monthsfrom date of manufacture.The shelf life for the CRP Calibrator Set, CRPCalibrator WR and CRP Calibrator HS is 24months from date of manufacture.			Same

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4. SUMMARY OF PERFORMANCE EVALUATION

The risk analysis method used to assess the impact of the modifications was a Failure Modes and Effects Analysis (FMEA).

Based on the risk analysis, the modification to the CRP Vario standardization method did not introduce any new risk to the performance of the assay.

To address the modification, verification and validation activities, which are summarized below, demonstrated that all of the acceptance criteria were met.

Linearity

Linearity evaluation followed the recommendations outlined in Clinical and Laboratory Standards Institute (CLSI) document EP06-A: Evaluation of the Linearity of Quantitative Measurement Procedures: a Statistical Approach: Approved Guideline.

A high CRP serum pool was mixed with different proportions of a low serum pool to generate 12 concentrations with each concentration level tested in triplicate determinations.

Linear results were compared to 2nd and 3rd order polynomial fits against a pre-specified allowable error.

The linearity range was found to extend up to:

16.00 mg/dL for the High Sensitivity Method
· 32.00 mg/dL for the Standard Method
48.00 mg/dL for the Wide Range Method

Method Comparison

The primary change in the candidate device, CRP Vario, from the predicated device is the modification in the traceability of the assay from CRM 470 to ERM-DA472/IFCC. As this change was introduced in 2010, the Sentinel predicate device, which is the CRP Vario on market, is now traceable to ERM-DA472/IFCC and therefore this predicate device cannot be used for the Method comparison study. As such, the method comparison study has been conducted using Beckman Coulter CRP Latex REF. OSR6199, which is traceable to CRM 470 (cleared under 510(k) K051564) on AU5800 platform (cleared under 510(k) K112412).

The Method Comparison was tested using the recommendations of CLSI Protocol EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples. Human serum samples, spanning the measuring range, were tested with the candidate CRP Vario assay (traceable to ERM-DA472) on an ARCHITECT c8000 analyzer and compared to the predicate method (Beckman Coulter CRP Latex REF. OSR6199, traceable to CRM 470) on a Beckman AU5800 analyzer. The correlation between the assays for each method is summarized below.

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Representative results analyzed using the Passing-Bablok regression method are summarized in Table 15-3 below. Please note that the regression analysis was performed taking the mean value of the predicate method (Beckman) versus the 1® replicate of the candidate method (c8000).

Method	Acceptance Criteria	Results
High SensitivityMethod	SlopeRn	0.95 – 1.05≥ 0.975≥ 100	Mean Beckman vs 1st rep c8000Slope 0.969 (0.964 – 0.974)Intercept 0.019 (0.001 – 0.036) mg/dLr 1.000n 111range: (0.01 – 15.71) mg/dL
StandardMethod	SlopeRn	0.95 – 1.05≥ 0.975≥ 100	Mean Beckman vs 1st rep c8000Slope 0.956 (0.925 – 0.997)Intercept -0.008 (-0.015 – -0.003) mg/dLr 1.000n 119range: (0.01 – 27.74) mg/dL
Wide RangeMethod	SlopeRn	0.95 – 1.05≥ 0.975≥ 100	Mean Beckman vs 1st rep c8000Slope 0.976 (0.944 – 0.993)Intercept -0.012 (-0.022 – -0.007) mg/dLr 1.000n 119range: (0.02 – 43.31) mg/dL

Table 15-3: Results of the Method Comparison between the Candidate Sentinel device
CRP Vario (LN. 6K26) and Beckman Coulter CRP Latex (REF. OSR6199).

Limit of Quantitation

A study was conducted to assess the sensitivity of CRP Vario High Sensitivity (HS), Standard (Std) and Wide Range (WR) methods.

The LoQ study was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP17-A2. The LOQ was determined using low-level analyte samples prepared at target levels concentrations of 0.08, 0.06, 0.05, 0.04. 0.03, 0.02, 0.01, and 0.005 mg/dL by diluting serum pool with SeraSub (a synthetic serum). Testing occurred over a minimum of 3 days, on 1 ARCHITECT c8000 System. Each sample was tested in a minimum of 10 replicates per run with 2 runs per day over 3 days, for a total of 60 replicates per sample.

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At a minimum the limit of quantitation shall be ≤ 0.03 mg/dL for hsCRP and ≤ 0.05 mg/dL for standard and Wide Range methods. The LOQ results are consistent with the original submission.

CONCLUSIONS

The differences between predicate and candidate do not impact the indications for use or technological characteristics.

The conclusions drawn from the nonclinical tests (discussed above) demonstrate the modified CRP Vario are as safe and effective as the predicate device.

The information submitted in the premarket notification is complete and supports a substantial equivalence decision.

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).