CardioPhase® hsCRP is an in-vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in human serum, and heparin and EDTA plasma by means of particle enhanced immunonephelometry using the BN II and BN ProSpec® System. In acute phase response, increased levels of plasma proteins, including C-reactive protein, is observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurements of hsCRP, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary syndromes.

Device Description

The CardioPhase hsCRP assay is an in vitro diagnostic reagent for the quantitative determination C-reactive protein, in human serum, and heparinized and EDTA plasma by means of particle-enhanced immunoassay determination. Polystyrene particles coated with monoclonal antibodies specific to human CRP are aggregated when mixed with samples containing CRP. These aggregates scatter a beam of light passed through the sample. The intensity of the scattered light is proportional to the concentration of the relevant protein in the sample. The result is evaluated by comparison with a standard of known concentration.

AI/ML Overview

This document describes the CardioPhase® hsCRP device, a C-reactive protein immunological test system, and a Special 510(k) submission for a change in its reference standard material from ERM-DA470 to ERM-DA474/IFCC.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state numerical acceptance criteria for all performance characteristics, but rather describes the studies performed and their satisfactory outcomes which imply meeting internal acceptance limits. For instance, for linearity, the stated ranges confirm the measuring range, implying that the observed linearity falls within acceptable deviations. For matrix comparison, high correlation coefficients and slopes close to 1 with intercepts close to 0 indicate acceptable equivalence.

Performance Characteristic	Acceptance Criteria (Implicit/Explicit)	Reported Device Performance
Detection Capabilities	Limit of Blank (LoB): Values below the respective Limit of Quantitation (LoQ). Limit of Detection (LoD): Greater than LoB and equal to or below LoQ. Limit of Quantitation (LoQ): An imprecision goal of less than 20% CV. (Specific numerical LoB/LoD not provided as acceptance criteria, but derived from the study.)	LoB: All results measured on blank samples yielded results below the respective LoQ. LoD: Calculated parametrically, greater than LoB and equal to or below LoQ. LoQ: Set to 0.094 mg/L based on the sample/instrument/reagent lot combination with the highest imprecision observed in the study (<11% CV), meeting the <20% CV goal.
Linearity	Deviation between mean measured value and predicted value of weighted linear regression compared to predefined acceptance criteria. (Specific numerical acceptance criteria not explicitly stated).	CRP sensitive (CRP2): Linear range 0.151 - 10.89 mg/L (confirming measuring range of 0.16-10 mg/L). CRP (CRP1): Linear range 1.478 – 224 mg/L (confirming measuring range of 3.1-100 mg/L). This implies that the predefined acceptance criteria were met.
Method Comparison	The predicted bias between the predicate and candidate assay should be within acceptable limits for intended use. (Specific numerical acceptance criteria not explicitly stated but implied by the reported bias values).	CRP2: Predicted bias of 6.9% at 1 mg/L and 7.5% at 3 mg/L. CRP1: Predicted bias of 8.17% at 10 mg/L. These values are presented as satisfactory for demonstrating substantial equivalence.
Matrix Comparison	Equivalence for serum vs. EDTA plasma and serum vs. heparin plasma, indicated by slope close to 1, intercept close to 0, and high Pearson Correlation Coefficient (r). (Specific numerical acceptance criteria for slope, intercept, and r not explicitly stated but implied by the conclusion of equivalence).	CRP1: Slopes (0.972-1.018), Intercepts (-0.118-0.091), Pearson r (0.995-0.998). CRP2: Slopes (0.962-1.061), Intercepts (-0.132-0.072), Pearson r (0.970-0.983). Conclusion: Confirmed equivalence for serum and EDTA/lithium heparin plasma.
Traceability	Calibrator N Rheumatology Standard SL must be traceable to the IFCC European Reference Material ERM-DA474/IFCC.	N Rheumatology Standard SL is traceable to Siemens internal Master Calibrator which is directly traceable to ERM-DA474/IFCC.
Substantial Equivalence	The modified device's performance should be substantially equivalent to the predicate device in terms of intended use, design, basic scientific principle, and performance, and the change should not affect safety and efficacy.	The presented performance data and the conclusion that "The modified device, CardioPhase hsCRP traceable to ERM-DA474/IFCC, is substantially equivalent to the predicate device... based on intended use design, and basic scientific principle and performance."

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

Detection Capabilities (LoB, LoD, LoQ):
- LoB: Five (5) independent analyte-free samples. Conducted with one (1) BN ProSpec System, one (1) BNII System, three (3) different reagent lots, one (1) calibrator lot, five (5) individual aliquots of each sample, and determination on three (3) days. This protocol resulted in 75 measurements per reagent lot, a total of 450 measurements (including the two workflows) on each of the two (2) analyzers, resulting in 900 measurements overall.
- LoD/LoQ: Serum samples with concentrations ranging from approximately 0.05 mg/L to 0.26 mg/L CRP. Five replicates of six patient samples were run once per day for five days using three hsCRP Reagent lots on one BNProSpec and one BN II, totaling 1080 determinations.
- Data Provenance: Not explicitly stated (e.g., country of origin). The samples are referred to as "analyte-free" and "patient samples" (serum), implying clinical relevance and likely of human origin. The study appears to be prospective as it was specifically designed for this evaluation.
Linearity:
- Sample Size: A high CRP serum pool was mixed with a low serum pool to generate 13 concentrations. Each level was tested in four-fold determination.
- Data Provenance: Not explicitly stated (e.g., country of origin). The samples are described as "serum pool," implying human origin. The study appears to be prospective.
Method Comparison:
- Sample Size: Native samples in the range of 0.27 and 11.90 mg/L for CRP2 and native samples in the range of 3.87 and 61.40 mg/L for CRP1. The exact number of samples is not explicitly given, but it implies a sufficient number to perform linear regression and bias calculations across the specified ranges.
- Data Provenance: Not explicitly stated (e.g., country of origin). Native samples imply human origin. The study appears to be prospective for this comparison.
Matrix Comparison:
- Sample Size: For each sample type (EDTA plasma and lithium heparin plasma compared to serum), a total of 60 native samples spanning the measuring range were evaluated.
- Data Provenance: Not explicitly stated (e.g., country of origin). Native samples imply human origin. The study appears to be prospective.

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

For this in-vitro diagnostic device (quantitative determination of C-reactive protein), "ground truth" is typically established by reference methods or gravimetrically prepared standards with known concentrations, or by comparison to a reference standard material.

Traceability and Standardization: The ground truth for this device is primarily established by its traceability to the IFCC European Reference Material ERM-DA474/IFCC, which is "certified for C-reactive protein measurements." This reference material serves as the "expert" or definitive standard.
No human expert panel for ground truth: Unlike image-based diagnostic devices, this type of immunoassay does not involve human experts establishing a "ground truth" based on interpretations (e.g., radiologists labeling images). The "ground truth" is analytical and defined by international reference standards.

4. Adjudication Method for the Test Set

Not applicable in the conventional sense. For an in-vitro diagnostic assay that measures a quantitative analyte, the "ground truth" is the certified value assigned to reference materials or the result from a highly accurate reference method. There is no subjective interpretation by multiple human adjudicators in the way there would be for an imaging diagnosis.

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

No. This is an in-vitro diagnostic (IVD) device for quantitative measurement of a biomarker (CRP). MRMC studies are typically performed for devices that involve human interpretation, such as imaging AI applications, to assess how AI assistance impacts human reader performance. This device does not have a "human reader" component in that context.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, entirely. The entire performance evaluation (detection capabilities, linearity, method comparison, matrix comparison) demonstrates the standalone performance of the CardioPhase® hsCRP assay system (reagent and instrument) in measuring CRP levels. The device itself, once calibrated, provides a quantitative result without human-in-the-loop performance influencing the measurement. The human role is in operating the instrument and interpreting the numerical result in a clinical context, but not in directly influencing the measurement itself.

7. Type of Ground Truth Used

The ground truth used is primarily certified reference materials (ERM-DA474/IFCC) and comparative analysis against a previously cleared predicate device (which itself was traceable to ERM-DA470) which acts as a well-established reference. The "ground truth" for the calibrator N Rheumatology Standard SL is its traceability to the Siemens internal Master Calibrator, which in turn is directly traceable to ERM-DA474/IFCC.

8. Sample Size for the Training Set

Not applicable. This document describes the performance evaluation of a change to an existing in-vitro diagnostic reagent and its calibrator. This is not a machine learning or AI-based device that typically requires a "training set" in the context of model development. The characterization studies described are for analytical performance verification of the assay system, rather than training a computational algorithm.

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

Not applicable, as there is no "training set" for this type of IVD device.

Summary

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December 16, 2022

Siemens Healthcare Diagnostics Products GmbH Martina Pfeiff Regulatory Affairs Manager Emil-von-Behring Str. 76 Marburg, 35041 Germany

Re: K212559

Trade/Device Name: CardioPhase® hsCRP Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: NQD Dated: June 22, 2022 Received: June 23, 2022

Dear Martina Pfeiff:

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/cfpmp/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 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

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https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) 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 medical devices and radiation-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,

Digitally signed by Paula Paula Caposino -S Caposino -S Date: 2022.12.16 10:44:12 -05'00'

Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

K212559

Device Name CardioPhase® hsCRP

Indications for Use (Describe)

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary per 21 CFR 807.92 Type of 510(k): Special 510(k)

This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K212559

1. Submitter

Siemens Healthcare Diagnostics Products GmbH Emil-von-Behring-Str. 76 35041 Marburg, Germany

Contact Person :	Martina Pfeiff
Email :	martina.pfeiff@siemens-healthineers.com
Phone:	+49 (174) 3319336
Fax:	+49 (6421) 394977
Date of Preparation:	June 23, 2022

2. Device Information

Proprietary Name:	CardioPhase® hsCRP
Common or Usual Name:	C-reactive protein immunological test system
Product Code:	NQD
Classification Name:	system, test, C-Reactive Protein per 21CFR866.5270
Regulatory Class:	II
510(k) Review Panel:	Immunology (82)

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Special 510(k) CardioPhase hsCRP Change in Reference Standard Material

3. Legally Marketed Unmodified / Predicate Devices

Cleared for use on Siemens' BN Systems under K033908 on January 22, 2004 as an invitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in human serum, and heparin and EDTA plasma by means of particle enhanced immunonephelometry using the BN Systems.

Trade Name	Common/UsualName	Classification	ProductCode	Panel	FDAclearance
Cardio PhasehsCRP	C-reactive proteinimmunological testsystem	Class II per21CFR866.5270	NQD	Immunology(82)	K964527*K991385 K033908

Clearance of N Rheumatology Standard SL (calibrator used with above mentioned reagent)

4. Device Description / Test Principle

Polystyrene particles coated with monoclonal antibodies specific to human CRP are aggregated when mixed with samples containing CRP. These aggregates scatter a beam of light passed through the sample. The intensity of the scattered light is proportional to the concentration of the relevant protein in the sample. The result is evaluated by comparison with a standard of known concentration.

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5. Intended Use / Indications for Use

CardioPhase hsCRP assay

CardioPhase hsCRP is an in-vitro diagnostic reagent for the quantitative determination of C-reactive protein (CRP) in human serum, and heparin and EDTA plasma by means of particle enhanced immunonephelometry using the BN II and BN ProSpec System. In acute phase response, increased levels of a number of plasma proteins, including Creactive protein, is observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. High sensitivity CRP (hsCRP) measurements may be used as an independent risk marker for the identification of individuals at risk for future cardiovascular disease. Measurements of hsCRP, when used in conjunction with traditional clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for recurrent events, in patients with stable coronary disease or acute coronary syndromes.

CardioPhase hsCRP consists of a suspension of polystyrene particles coated with mouse monoclonal antibodies (< 0.016 q/L) to CRP.

N Rheumatology Standard SL

N Rheumatology Standard SL is used for the establishment of reference curves for the immunonephelometric determination of C-reactive protein on the BN II and BN ProSpec Systems. This calibrator consists of a mixture of human sera and elevated concentrations of CRP.

6. Special Conditions for Use Statements

For prescription use only.

AHA/CDC Expert Panel Recommendations:

hsCRP levels should not be substituted for assessment of traditional cardiovascular risk factors. Application of management quidelines for acute coronary syndromes should not be dependent on hsCRP levels.

In patients with stable coronary disease or acute coronary syndromes, hsCRP measurement may be useful as an independent marker of prognosis.

When using the assay for risk assessment, patients with persistently unexplained, marked elevation of hsCRP (> 10 mg/L) after repeated testing should be evaluated for noncardiovascular etiologies.

The expert panel recommends against screening of the entire adult population for hsCRP as a public health measure.

Patients with evidence of active infection, systemic inflammatory processes or trauma should not be tested for cardiovascular disease risk assessment until these conditions have abated.

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Application of secondary prevention measures should not depend on hsCRP determination, but rather an array of risk factors (global risk assessment). Serial measurements of CRP should not be used to monitor effects of treatment. Two separate CRP measurements (optimally two weeks apart) should be obtained before performing risk assessment, due to within-subject CRP variability. Measurement of hsCRP is an independent marker of risk.

hsCRP levels may be useful in motivating patients to improve lifestyle behaviors.

7. Special instrument requirements:

BN II System (K943997) BN ProSpec System(K001647) BN Systems (nephelometry)

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8. Technological characteristics

Similarities and Differences to the predicate:

The following is a table with a comparison of the similarities and differences between the proposed ERM-DA474/IFCC standardized CardioPhase hsCRP assay to the predicate device ERM-DA470 standardized CardioPhase hsCRP assay.

Table 8.-1: Similarities and Differences between proposed ERM-DA474/IFCC standardized and predicate ERM-DA470 standardized CardioPhase hsCRP

	Predicate	Proposed Device
	Siemens HealthcareCardioPhase hsCRPERM-DA470 standardized(K033908)	Siemens HealthcareCardioPhase hsCRPERM-DA474/IFCCstandardized
Indications for Use	cardiac risk assessment andinjury/inflammation	Same
Sample Type	Human serum, heparin and EDTAplasma	Same
Reagent Packaging	3 x 1 mL	Same
Units	mg/L	Same
Detection Method	Nephelometry	Same
Measurement	Quantitative	Same
Detection Antibody	Mouse monoclonal antibodies	Same
Reagent Composition	Polystyrene particles coated withmonoclonal antibodies	Same
Calibrator	N Rheumatology Standard SL	Same
Traceability/Standardization	ERM-DA470	ERM-DA474/IFCC
Calibrator Levels	One level	Same
Analytical Measuring Range	CRP sensitive (CRP2) = 0.16 - 10 mg/LCRP (CRP1)= 3.1 – 200 mg/L	CRP sensitive (CRP2) = 0.16 - 10 mg/LCRP (CRP1)= 3.1 – 100 mg/L
Expected Values	Healthy Individuals ≤ 3 mg/L	Same
	Cardiac Risk Stratification accordingto AHA/CDC Scientific Statement:Relative Risk &p>

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The differences between the predicate device and proposed device do not result in a change to the intended use, the indications for use, or to safety and efficacy when used according to the product labeling.

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9. Summary of Design Control Activities

A risk analysis was performed with risks identified. Mitigation of risk to acceptable levels was achieved through verification activities summarized below.

9.1 Risk Analysis

Risk analysis was performed according to the ISO14971:2019 standard, Medical Devices - Application of Risk Management to Medical Devices. The change to the standard reference material for the CardioPhase hsCRP assay is the only change made to the test system. The reagents, packaging and instruments used for analysis remain unchanged. The labeling of the package insert for N Rheumatology Standard SL was updated including the reference to the new reference material ERM-DA474.

Each difference was analyzed, and its effect identified. Severity and probability were estimated by risk class. Risks were mitigated to the degree acceptable.

9.2. Verification Activities

Based on the results of the risk analysis, verification activities were identified, pertinent studies were determined and acceptance criteria established. The following studies were necessary to determine substantial equivalence:

9.3. Performance Studies

9.3.1 Detection Capabilities

The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) were determined according to the CLSI document EP17-A2:2012, Evaluation of Detection Capability for Clinical CLSI Laboratory Measurement Procedures: Approved Guideline— Second Edition. The LoB and LoD estimates were evaluated separately for each reagent lot on each BN System and the reagent lot and analyzer combination yielding the highest value was used for the LoB, LoD and LoQ claims.

The LoB study was performed with five (5) independent analyte-free samples. The LoB study was carried out with one (1) BN ProSpec System, one (1) BNII System, three (3) different reagent lots, one (1) calibrator lot, five (5) analyte-free samples, one (1) single determination of five (5) individual aliquots of each sample on three (3) days and with one (1) trained operator. This protocol results in 75 measurements per reagent lot, a total of 450 measurements (including the two workflows) on each of the two (2) analyzers resulting in 900 measurements overall.

All results measured on blank samples for the LoB study yielded results below the respective LoQ.

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To determine the limit of the detection (LoD) and Limit of Quantitation (LoQ), serum samples with concentrations ranging from approximately 0.05 mg/L to 0.26 mg/L CRP were prepared. Five replicates of six patient samples were run once per day for five days using three hsCRP Reagent lots on one BNProSpec and one BN II totaling 1080 determinations. The Limit of Detection (LoD) was calculated parametrically following the recommendations in the CLSI guideline. The LoD is greater than Limit of Blank and equal or below Limit of Quantitation

The Limit of Quantitation (LoQ) was calculated using the data generated for the LoD study and was based on an imprecision goal of less than 20% CV. The LoQ was set to 0.094 mg/L based on the sample/instrument/reagent lot combination with the highest imprecision observed in the study (<11%CV).

9.3.2 Linearity

A linearity study was performed according to CLSI EP06-Ed2, Evaluation of the Linearity of Quantitative Measurement Procedures: A statistical Approach.

A high CRP serum pool was mixed with different proportions of a low serum pool to generate 13 concentrations covering the measuring ranges of CRP sensitive - CRP2 (0,16 -10 mg/L) and CRP - CRP1 (3.1-100 mg/L with each level tested in four-fold determination on BN ProSpec and BN II System.

For result calculation the deviation between the mean measured value and the predicted value of a weighted linear regression was compared to the predefined acceptance criteria.

The following linear ranges were found confirming the upper end of the measuring ranges:

CRP sensitive (CRP2): 0.151 - 10.89 mg/L (measuring range:0.16-10 mg/L) 1.478 – 224 mg/L (measuring range: 3.1-100 mg/L) CRP (CRP1):

9.3.3 Method Comparison

A method comparison using native samples in the range of 0.27 and 11.90 mg/L between the CardioPhase® hsCRP assay (cleared in 2003 under premarket clearance K033908; standardized to ERM-DA470, x-axis) and candidate assay (standardized to ERM-DA474/IFCC, y-axis) produced a predicted bias of 6.9 % at 1 mg/L, and 7.5 % at 3 mg/L for CRP2 and using native samples in the range of 3.87 and 61.40 mg/L between the CardioPhase® hsCRP assay (cleared in 2003 under premarket clearance K033908; standardized to ERM-DA470, x-axis) and candidate assay (standardized to ERM-DA474/IFCC, y-axis) produced a predicted bias of 8.17% at 10 mg/L for CRP1.

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9.4 Matrix Comparison

Siemens conducted a study to confirm equivalence for serum and EDTA plasma and for serum and lithium heparin plasma for the ERM-DA474/IFCC standardized CardioPhase hsCRP assay.For each sample type, a total of 60 native samples spanning the measuring range were evaluated. The data was collected using one instrument (BNProSpec and BNII System), and 3 lots of reagent. A Passing-Bablok linear regression analysis was performed comparing the material used in the studies (serum) to EDTA and lithiumheparinized plasma.

The results for one reagent lot are shown in the tables below.

Application	N	Slope(95% CI)	Intercept(95% CI)	PearsonCorrelationCoefficient (r)
CRP1 withCardioPhasehsCRP on BNPSSystemSerum vs. EDTAPlasma	60	0.972(0.954 to 0.992)	0.091(-0.218 to 0.281)	0.998
CRP1 withCardioPhasehsCRP on BN IISystemSerum vs. EDTAPlasma	60	0.986(0.947 to 1.012)	0.068(-0.186 to 0.276)	0.997
CRP1 withCardioPhasehsCRP onBNProSpecSystemSerumvs. Heparin Plasma	60	0.989(0.963 to 1.013)	-0.097(-0.470 to 0.109)	0.995
CRP1 withCardioPhasehsCRP on BN IISystemSerum vs. HeparinPlasma	60	1.018(0.989 to 1.045)	-0.118(-0.363 to 0.044)	0.995

Table 9.4.1: Results matrix comparison-CRP (CRP1)

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Application	N	Slope(95% CI)	Intercept(95% CI)	PearsonCorrelationCoefficient (r)
CRP2 withCardioPhasehsCRP on BNPSSystemSerum vs. EDTAPlasma	74	1.056(1.009 to 1.103)	-0.014(-0.132 to 0.070)	0.974
CRP2 withCardioPhasehsCRP on BN IISystemSerum vs. EDTAPlasma	74	1.061(1.016 to 1.118)	-0.009(-0.118 to 0.072)	0.970
CRP2 withCardioPhasehsCRP onBNProSpec SystemSerum vs. HeparinPlasma	74	0.967(0.931 to 1.002)	-0.035(-0.136 to 0.062)	0.983
CRP2 withCardioPhasehsCRP on BN IISystemSerum vs. HeparinPlasma	74	0.962(0.913 to 0.997)	-0.024(-0.123 to 0.054)	0.979

Table 9.4.1: Results matrix comparison-CRP sensitive(CRP2)

The results of the matrix comparison study confirm equivalence for serum and EDTAplasma and for serum and lithium heparin plasma for the ERM-DA474/IFCC standardized CardioPhase hsCRP assay.

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9.5 Traceability

The calibration of the assay is traceable to the IFCC European Reference Material ERM-DA474/IFCC, certified for C-reactive protein measurements.

9.5.1 Calibrator Traceability

N Rheumatology Standard SL is traceable to Siemens internal Master Calibrator which is directly traceable to ERM-DA474/IFCC.

10. Comments on Substantial Equivalency

The reagents for the proposed devices and the cleared devices are identical in composition, labeling and packaging. Comparative testing was performed, and the results obtained demonstrate substantial equivalent performance.

The use of the reagent with N Rheumatology Standard SL traceable to ERM-DA474/IFCC does not affect safety and efficacy when used according to the product labeling.

11. Conclusion

The modified device, CardioPhase hsCRP traceable to ERM-DA474/IFCC, is substantially equivalent to the predicate device, CardioPhase hsCRP traceable to ERM-DA470 based on intended use design, and basic scientific principle and performance.

Results from the risk analysis and design control activities with comparative testing support 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).