CardioPhase® hsCRP

K232624 · Siemens Healthcare Diagnostic Products GmbH · DCN · Nov 27, 2023 · Immunology

Device Facts

• Record ID: K232624
• Device Name: CardioPhase® hsCRP
• Applicant: Siemens Healthcare Diagnostic Products GmbH
• Product Code: DCN · Immunology
• Decision Date: Nov 27, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5270
• Device Class: Class 2

Indications for Use

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 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 Story

CardioPhase hsCRP is an in-vitro diagnostic reagent for quantitative CRP measurement in human serum and plasma. It utilizes polystyrene particles coated with mouse monoclonal antibodies specific to human CRP. When mixed with patient samples, CRP-antibody binding causes particle aggregation; these aggregates scatter light. The intensity of scattered light, measured via immunonephelometry on BN II or BN ProSpec systems, is proportional to CRP concentration. Results are determined by comparison against known standards. The device supports two workflows: conventional CRP1 (3.1–200 mg/L) and high-sensitivity CRP2 (0.16–10 mg/L). Used in clinical laboratories by trained personnel to assist in diagnosing inflammatory conditions and assessing cardiovascular risk. Output provides quantitative CRP levels, aiding clinicians in evaluating infection, tissue injury, and cardiovascular prognosis.

Clinical Evidence

Bench testing only. Method comparison study performed per CLSI EP09c using 129 native serum samples across three reagent lots. Passing-Bablok regression analysis showed slopes between 0.959 and 1.032 and Pearson correlation coefficients (r) of 0.994–0.996. Predicted bias at concentrations of 10, 100, 150, and 200 mg/L was ≤ ± 6%. Linearity, precision, specificity, and detection limits were previously established in K212559.

Technological Characteristics

Ready-to-use suspension of polystyrene particles coated with mouse monoclonal antibodies (< 0.016 g/L) and preservatives. Principle: Particle-enhanced immunonephelometry. Detection wavelength: 840 nm. Traceability: ERM-DA474/IFCC. Compatible with BN II and BN ProSpec systems. Analytical measuring range: 3.1–200 mg/L (CRP1) and 0.16–10 mg/L (CRP2).

Indications for Use

Indicated for quantitative determination of C-reactive protein (CRP) in human serum, heparin plasma, and EDTA plasma. Used for detection/evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. High sensitivity (hsCRP) used as independent risk marker for future cardiovascular disease and as prognostic marker for recurrent events in patients with stable coronary disease or acute coronary syndromes.

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

• RCRP Flex® reagent cartridge (K221119)

Submission Summary (Full Text)

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FDA U.S. FOOD &amp; DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K232624

B Applicant

Siemens Healthcare Diagnostic Products GmbH

C Proprietary and Established Names

CardioPhase hsCRP

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DCN, NQD | Class II | 21 CFR 866.5270 - C-Reactive Protein Immunological Test System | IM - Immunology |

## II Submission/Device Overview:

A Purpose for Submission:

Extension of the upper limit of the measuring range of the conventional CRP assay range (CRP1) defined in K212559.

B Measurand:

C-reactive protein

C Type of Test:

Quantitative immunonephelometric assay

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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## III Intended Use/Indications for Use:

### A Intended Use(s):

See Indications for Use below.

### B Indication(s) for Use:

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 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.

### C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only
For in vitro diagnostic use.

### D Special Instrument Requirements:

BN II System and BN ProSpec

## IV Device/System Characteristics:

### A Device Description:

CardioPhase hsCRP reagent is ready-to-use and consists of a suspension of polystyrene particles coated with mouse monoclonal antibodies (&lt; 0.016 g/L) specific to human CRP and preservatives.

Kit Contents:
- 5 x 5 mL CardioPhase hsCRP Reagent
- or-
- 3 x 2 mL CardioPhase hsCRP Reagent

Materials required but not provided:
- N Rheumatology Standard SL
- N/T Rheumatology Controls SL/1 and SL/2 and/or Apolipoprotein Control Serum CHD
- N Supplementary Reagent/Precipitation
- N Diluent
- BN II Evaporation Stoppers (optional)
- Additional materials and supplies as described in the BN System Instruction Manual

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B Principle of Operation:

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. Two measuring range settings are available: the conventional CRP1 workflow (3.1 – 200 mg/L) and the high sensitivity CRP2 workflow (0.16 – 10 mg/L).

V Substantial Equivalence Information:

A Predicate Device Name(s):

RCRP Flex reagent cartridge

B Predicate 510(k) Number(s):

K221119

C Comparison with Predicate(s):

| Device & Predicate Device(s): | K232624
(Candidate Device) | K221119
(Predicate) |
| --- | --- | --- |
| Device Trade Name | CardioPhase hsCRP | RCRP Flex reagent cartridge |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | 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 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 | The C-Reactive Protein Extended Range (RCRP) method used on the Dimension clinical chemistry system is an in vitro diagnostic test intended for the quantitative determination of CRP in human serum and plasma (lithium heparin). Measurement of C-Reactive Protein is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. |

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| Device & Predicate Device(s): | K232624
(Candidate Device) | K221119
(Predicate) |
| --- | --- | --- |
| | 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. | |
| Traceability | ERM-DA474/IFCC | Same |
| General Device Characteristic Differences | | |
| Test Principle | Particle-enhanced Immunonephelometry read at 840 nm | Particle-enhanced Immunoturbidometry read at 340 nm |
| Analytical Measuring Range | 3.1 – 200 mg/L (workflow CRP1)
0.16 – 10 mg/L (workflow CRP2) | 5.0 – 250.0 mg/L |
| Calibrators | One level diluted to seven levels | Five individual levels |
| Sample Matrices | Serum, lithium heparin plasma, and EDTA heparin plasma | Serum, lithium heparin plasma |

VI Standards/Guidance Documents Referenced:

CLSI EP09c 3rd Edition: Measurement Procedure Comparison and Bias Estimation Using Patient Samples

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:
Previously established.

2. Linearity:
Previously determined under K212559. The linear range was found to be 1.48 – 224 mg/L for CRP1, supporting the linearity of the measuring range up to 200 mg/L.

3. Analytical Specificity/Interference:
Previously established.

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4. Assay Reportable Range:

Previously established.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

The assay is traceable to ERM DA474/IFCC.

Stability was previously established.

6. Detection Limit:

The detection limits were established in K212559.

7. Assay Cut-Off:

Not applicable for CRP1

## B Comparison Studies:

1. Method Comparison with Predicate Device:

A method comparison study was performed to evaluate the comparability between the performance of the CRP1 method of the CardioPhase hsCRP on the BN II System and the RCRP Flex assay on the Dimension clinical chemistry system following CLSI EP09c. A cohort of 129 native serum samples was tested on one lot of the predicate and on three lots of the CardioPhase using the CRP1 method. Samples falling outside the measuring range of either assay were removed from the analysis and the results were determined by Passing-Bablok regression analysis. For each lot, the predicted bias at CRP concentrations of 10 mg/L, 100 mg/L, 150 mg/L and 200 mg/L was ≤ ± 6%. The results of each lot are shown below:

| | Lot 1 | Lot 2 | Lot 3 |
| --- | --- | --- | --- |
| Number of Samples (n) | 119 | 116 | 113 |
| Sample Range (mg/L) | 5.52 – 197.75 | 5.38 – 199.15 | 5.50 – 199.50 |
| Slope
(95% Confidence Interval) | 0.959
(0.941 – 0.982) | 0.995
(0.981 – 1.008) | 1.032
(1.015 – 1.044) |
| Intercept
(95% Confidence Interval) | 0.932
(0.490 – 1.323) | 0.584
(0.228 – 0.942) | -0.070
(-0.324 – 0.340) |
| Pearson Correlation (r) | 0.994 | 0.996 | 0.994 |
| Coefficient of Determination (r²) | 0.989 | 0.991 | 0.989 |

2. Matrix Comparison:

Previously established.

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C Clinical Studies:

1. Clinical Sensitivity and Specificity:
Not applicable for the CRP1 method.

D Clinical Cut-Off:
Not applicable.

E Expected Values/Reference Range:
Previously established.

VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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