DIMENSION VISTA CRP FLEX REAGENT CARTRIDGE, PROTEIN 2 CALIBRATOR, CONTROL LOW AND CONTROL HIGH

K061825 · Dade Behring, Inc. · DCN · Sep 6, 2006 · Immunology

Device Facts

• Record ID: K061825
• Device Name: DIMENSION VISTA CRP FLEX REAGENT CARTRIDGE, PROTEIN 2 CALIBRATOR, CONTROL LOW AND CONTROL HIGH
• Applicant: Dade Behring, Inc.
• Product Code: DCN · Immunology
• Decision Date: Sep 6, 2006
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5270
• Device Class: Class 2

Intended Use

The CRP method is an in vitro diagnostic test for the quantitative measurement of C-reactive protein (CRP) in human serum and heparinized plasma by means of particle enhanced immunonephelometry on the Dimension Vista™ System. In acute phase response, increased levels of a number of plasma proteins, including C-reactive protein, are observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, and inflammatory disorders. Protein 2 Calibrator is an in vitro diagnostic product for the calibration of the C-reactive protein (CRP) method on the Dimension Vista™ System. Protein 2 Control L and H are for use as assayed intra laboratory quality controls for the assessment of precision and analytical bias in determination of C-reactive protein (CRP) on the Dimension Vista™ System.

Device Story

The Dimension Vista™ CRP Flex® reagent cartridge utilizes polystyrene particles coated with monoclonal anti-human CRP antibodies. When mixed with patient serum or heparinized plasma, CRP in the sample causes particle aggregation. The system passes a light beam through the sample; the intensity of scattered light is measured via immunonephelometry. This intensity is proportional to CRP concentration. The system evaluates results against a known standard. Used in clinical laboratory settings by trained personnel. Output provides quantitative CRP levels to assist clinicians in diagnosing and monitoring inflammatory conditions, infections, and tissue injury. System includes liquid human serum-based calibrators and quality controls to ensure analytical precision and bias assessment.

Clinical Evidence

Bench testing only. Precision evaluated per CLSI EP05-A2 (20 days, duplicate, twice daily); repeatability CVs 3.7-5.3%, within-lab CVs 3.8-6.7%. Linearity confirmed (slope 1.041, r=0.995). Interference testing (HIL) showed <10% bias for hemoglobin, bilirubin, and lipemia. Method comparison against predicate (n=140) yielded slope 0.985, intercept -0.353, r=0.997. No hook effect up to 1347.9 mg/L.

Technological Characteristics

Reagent: Polystyrene particles coated with monoclonal anti-human CRP antibodies. Measurement principle: Particle-enhanced immunonephelometry. System: Dimension Vista™ automated analyzer. Calibrators/Controls: Liquid human serum-based products. Connectivity: Integrated system component.

Indications for Use

Indicated for quantitative measurement of C-reactive protein (CRP) in human serum and heparinized plasma to aid in detection and evaluation of infection, tissue injury, and inflammatory disorders. Used on the Dimension Vista™ System.

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

• Dade Behring CardioPhase® hsCRP assay (k033908)
• N Rheumatology Standard SL (k964527)
• N/T Rheumatology Control SL (k962373)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
k061825

B. Purpose for Submission:
New Submission

C. Measurand:
C-Reactive Protein

D. Type of Test:
Quantitative Immuno-nephelometric assay

E. Applicant:
Dade Behring, Inc.

F. Proprietary and Established Names:
Dimension Vista CRP Flex Reagent Cartridge, Protein 2 Calibrator, Control Low And Control High

G. Regulatory Information:
1. Regulation section:
21CFR§-866.5270-C-reactive protein immunological test system
21CFR§-862.1150-Calibrator
21CFR§-862.1660-Quality control material (assayed and unassayed)
2. Classification:
Class II, II, and 1 reserved, respectively
3. Product code:
DCN- System, Test, C-Reactive Protein
JIX - Calibrator, Multi-Analyte Mixture
JJY - Multi-Analyte Controls, All Kinds (Assayed And Unassayed)
4. Panel:
Chemistry (75)

H. Intended Use:
1. Intended use(s):
See indications for use below

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2. Indication(s) for use:

Dimension Vista™ CRP Flex® reagent cartridge:

The CRP method is an in vitro diagnostic test for the quantitative measurement of C-reactive protein (CRP) in human serum and heparinized plasma by means of particle enhanced immunonephelometry on the Dimension Vista™ System. In acute phase response, increased levels of a number of plasma proteins, including C-reactive protein, are observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, and inflammatory disorders.

Dimension Vista™ Protein 2 Calibrator:

Protein 2 Calibrator is an in vitro diagnostic product for the calibration of the C-reactive protein (CRP) method on the Dimension Vista™ System.

Dimension Vista™ Protein 2 Control L and Dimension Vista™ Protein 2 Control H:

Protein 2 Control L and H are for use as assayed intra laboratory quality controls for the assessment of precision and analytical bias in determination of C-reactive protein (CRP) on the Dimension Vista™ System.

3. Special conditions for use statement(s):

Prescription use

4. Special instrument requirements:

Dade Dimension Vista™ System

I. Device Description:

Reagents are in the following cassette format

| Wells | Form | Ingredient | Concentration | Source |
| --- | --- | --- | --- | --- |
| 1-8 | Liquid | CRP Supplement Reagent: | | |
| | | Phosphate buffer | | |
| | | Polidocanol | 1.9 g/L | |
| | | | | |
| 9-12 | Liquid | CRP Reagent: | | |
| | | Polystyrene particles | | |
| | | Monoclonal antibodies | 1 g/L | |
| | | | 13 mg/L | Mouse |

PROT2 CAL is a liquid, human serum based product containing C-reactive protein.

CONROL L &amp;H are liquid, human serum based product containing C-reactive protein

J. Substantial Equivalence Information:

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1. Predicate device name(s):
Dade Behring CardioPhase® hsCRP assay, N Rheumatology Standard SL and N/T Rheumatology Control SL

2. Predicate 510(k) number(s):
k033908, k964527, k962373

3. Comparison with predicate:

| Feature | Dade Behring CardioPhase® hsCRP Assay | Dimension Vista™ CardioPhase® hsCRP Assay |
| --- | --- | --- |
| 1. Intended 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 BN™ Systems. 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. | The CRP method is an in vitro diagnostic test for the quantitative measurement of C-reactive protein (CRP) in human serum and heparinized plasma by means of particle enhanced immunonephelometry on the Dimension Vista™ System. In acute phase response, increased levels of a number of plasma proteins, including C-reactive protein, are observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, and inflammatory disorders. |
| 2. Principle: | Same | Same |
| 3. Standardization: | Same | Same |
| 4. Antibody: | Same | Same |
| 5. Reportable Range: | 0.16 – 200 mg/L | 3.1 – 190 mg/L |
| 6. Calibrator: | N Rheumatology Standard SL | Dimension Vista™ Protein 2 Calibrator |
| Form: | Liquid, human serum | Liquid, human serum |
| Constituents: | RF, ASL and CRP | CRP |

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| Feature | Dade Behring CardioPhase®
hsCRP Assay | Dimension Vista™ CardioPhase®
hsCRP Assay |
| --- | --- | --- |
| Traceable to: | known as CRM 470 | CRM 470 |
| Levels: | 1 | 1 |
| 7. Control: | N/T Rheumatology Control SL 1/2 | Dimension Vista™ high sensitivity CRP Control L and H |
| Form: | Liquid, human serum | Liquid, human serum |
| Constituents: | RF, ASL and CRP | CRP |
| Traceable to: | International Reference Preparation – RF and ASL
CRM 470 - CRP | CRM 470 |
| Levels | Low and High | Low and High |
| 8. Analyzer: | BN™ Systems | Dimension Vista™ System |

K. Standard/Guidance Document Referenced (if applicable):
CLSI - Evaluation of Precision Performance of Clinical Chemistry Devices - EP05-A2
CLSI - Interference Testing in Clinical Chemistry - EP07-A2

L. 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 respective protein in the sample. The result is evaluated by comparison with a standard of known concentration.

M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Precision testing was done in accordance with CLSI/NCCLS Approved Guideline for Evaluation of Precision Performance of Clinical Devices: EP5-A2. Specimens at each level were analyzed in duplicate, twice a day, for 20 days. The repeatability and within-lab standard deviations (SD) and percent coefficient of variation (%CV) were calculated by the analysis of variance method. The data are summarized below.

CRP Precision Data Summary

| Material | Mean mg/L | Repeatability SD (%CV) | Within-Lab SD (%CV) |
| --- | --- | --- | --- |
| PROT2 CON L | 11.91 | 0.57 (4.8) | 0.72 (6.0) |
| PROT2 CON H | 49.47 | 1.83 (3.7) | 2.14 (4.3) |
| Serum pool | 5.69 | 0.30 (5.3) | 0.38 (6.7) |
| Serum pool | 44.79 | 2.17 (4.9) | 2.32 (5.2) |
| Serum pool | 176.7 | 6.5 (3.7) | 6.8 (3.8) |

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b. Linearity/assay reportable range:

The reportable range if 3.1 – 190 mg/L is based on linearity and method comparison.

Linearity across the assay range was confirmed by testing serum samples with high concentrations of CRP. These samples were serially diluted with System Diluent down to the lower measuring range (171.6 to 4.8 mg/L). Each dilution was tested in replicates of five. Percent recovery was calculated using the formula: Mean of test/ expected concentration X 100. All dilutions met the acceptance criterion of recovery of 80 to 120%.

The linear regression [x-axis: theoretical concentration versus y-axis: measured concentration] was also calculated. The acceptance criteria of slope between 0.9 and 1.1 and correlation coefficient ≥0.95 were met. A summary of the linearity data is presented below.

| Slope | Intercept | Correlation Coefficient |
| --- | --- | --- |
| 1.041 | 1.745 | 0.995 |

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Standard values are assigned to a master calibrator lot using CRM 470. Values are then assigned to the commercial calibrator (human pooled at target concentration) verses master calibrator using three reference curves, 4 runs, 3 vials, 4 replicates per vial tested on two nephelometric instruments for a total of 144 measurements.

Control values are assigned to a master control lot using CRM 470. Values are then assigned to the commercial control (human pooled at target concentration) verses master control using three reference curves, 4 runs, 3 vials, 4 replicates per vial tested on two nephelometric instruments for a total of 144 measurements.

Standard stability is tested real time for stored at +2 to +8°C and opened/punctured on board instrument.

d. Detection limit:

Limit of Detection: 3.1 mg/L

The limit of detection represents the lower limit of the reportable range of CRP based on the sensitivity, functional sensitivity, and historical variability of the calibrator, which represents the lower cutoff point of the reportable range of CRP.

e. Analytical specificity:

HIL Interference

The CRP method was evaluated for interference according to CLSI/NCCLS EP7-A2. Bias is the difference in the results between the control sample (without the interferent) and the test sample (contains the interferent)

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expressed in percent. Bias exceeding $10\%$ is considered interference.

| Substance Tested | Substance Concentration | S. I. Units | CRP Concentration mg/L | Bias % |
| --- | --- | --- | --- | --- |
| Hemoglobin (hemolysate) | 1000 mg/dL | 0.62 mmol/L | 13.68 | -1 |
| Bilirubin (unconjugated) | 60 mg/dL | 1026 μmol/L | 13.70 | -6 |
| Bilirubin (conjugated) | 60 mg/dL | 1026 μmol/L | 13.70 | -1 |
| Lipemia (Triglycerides) | 1455 mg/dL | 16.44 mmol/L | 52.96 | -1 |

# Non Interfering Substances

The following substances do not interfere with the CRP method when present in serum and plasma at the concentrations indicated. Inaccuracies (biases) due to these substances are less than $10\%$ at CRP concentration of $3.09\mathrm{mg / L}$ to $125.47\mathrm{mg / L}$ .

| Substance | Test Concentration | S. I. Units |
| --- | --- | --- |
| Acetaminophen | 0.025 mg/dL | 1.66 μmol/L |
| Amikacin | 15 mg/dL | 256 μmol/L |
| Ammonium heparin | 3 U/mL | 3000 U/L |
| Ampicillin | 5.3 mg/dL | 152 μmol/L |
| Ascorbic acid | 5 mg/dL | 227 μmol/L |
| Caffeine | 6 mg/dL | 308 μmol/L |
| Carbamazepine | 3 mg/dL | 127 μmol/L |
| Chloramphenicol | 5 mg/dL | 155 μmol/L |
| Chlordiazepoxide | 1 mg/dL | 33.3 μmol/L |
| Chlorpromazine | 0.2 mg/dL | 6.27 μmol/L |
| Cholesterol | 500 mg/dL | 12.9 mmol/L |
| Cimetidine | 2 mg/dL | 79.2 μmol/L |
| Creatinine | 30 mg/dL | 2652 μmol/L |
| Dextran 40 | 6000 mg/dL | 1500 μmol/L |
| Diazepam | 0.5 mg/dL | 17.6 μmol/L |
| Digoxin | 5 ng/dL | 6.15 nmol/L |
| Erythromycin | 6 mg/dL | 81.6 μmol/L |
| Ethanol | 400 mg/dL | 86.8 mmol/L |
| Ethosuximide | 25 mg/dL | 1770 μmol/L |
| Furosemide | 6 mg/dL | 181 μmol/L |
| Gentamicin | 12 mg/dL | 251 μmol/L |
| Ibuprofen | 50 mg/dL | 2425 μmol/L |
| Immunoglobulin G (IgG) | 5 g/dL | 50 g/L |
| Lidocaine | 1.2 mg/dL | 51.2 μmol/L |
| Lithium chloride | 2.3 mg/dL | 3.2 mmol/L |
| Lithium heparin | 3 U/mL | 3000 U/L |

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| Substance | Test Concentration | S. I. Units |
| --- | --- | --- |
| Nicotine | 0.1 mg/dL | 6.2 μmol/L |
| Penicillin G | 25 U/mL | 25000 U/L |
| Pentobarbital | 8 mg/dL | 354 μmol/L |
| Phenobarbital | 10 mg/dL | 431 μmol/L |
| Phenytoin | 5 mg/dL | 198 μmol/L |
| Primidone | 4 mg/dL | 183 μmol/L |
| Propoxyphene | 0.2 mg/dL | 4.91 μmol/L |
| Protein Albumin | 6 g/dL | 60 g/L |
| Protein Total | 10 g/dL | 100 g/L |
| Rheumatoid Factor | 500 IU/mL | 500 IU/mL |
| Salicylic acid | 60 mg/dL | 4.34 mmol/L |
| Sodium heparin | 3 U/mL | 3000 U/L |
| Theophylline | 4 mg/dL | 222 μmol/L |
| Urea | 500 mg/dL | 83.3 mmol/L |
| Uric Acid | 20 mg/dL | 1190 μmol/L |
| Valproic acid | 50 mg/dL | 3467 μmol/L |

The CRP method shows no hook effect up to 1347.9 mg/L.

f. Assay cut-off:
See limit of detection above.

2. Comparison studies:

a. Method comparison with predicate device:
The Dimension Vista™ CRP assay was compared to the Dade Behring CardioPhase® hsCRP assay on the BN ProSpec® System by evaluating serum and plasma samples with concentrations ranging from 3.36 to 182.76 mg/L. Regression analysis of these results yielded the following equation:

Method Comparison Study

| | n | Slope | Intercept | Correlation Coefficient |
| --- | --- | --- | --- | --- |
| Dimension Vista™ CRP | 140 | 0.985 | -0.353 | 0.997 |

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b. Matrix comparison:

| Sample | Serum | Li Hep | Na Hep |
| --- | --- | --- | --- |
| 1 | 5.74 | 5.74 | 5.65 |
| 2 | 35.21 | 34.38 | 34.19 |
| 3 | 9.51 | 9.51 | 9.44 |
| 4 | 8.86 | 8.13 | 8.32 |
| 5 | 12.93 | 11.97 | 12.18 |
| 6 | 5.20 | 5.51 | 5.10 |
| 7 | 87.96 | 87.79 | 89.10 |
| 8 | 113.90 | 116.23 | 110.93 |
| 9 | 130.36 | 128.40 | 128.74 |
| 10 | 157.35 | 155.94 | 159.25 |
| 11 | 177.41 | 172.07 | 178.74 |
| Linear Regression vs Serum | | |
| --- | --- | --- |
| Slope: | 0.99 | 1.00 |
| Y-int: | 0.14 | -0.58 |
| r: | 1.000 | 1.000 |
| Syx: | 1.71 | 1.42 |
| Slope 95% CI | | |
| Low: | 0.97 | 0.99 |
| Slope 95% CI | | |
| High: | 1.00 | 1.02 |

3. Clinical studies:

a. Clinical Sensitivity: Not Applicable
b. Clinical specificity: Not Applicable
c. Other clinical supportive data (when a. and b. are not applicable): Not Applicable

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4. Clinical cut-off: Not Applicable
5. Expected values/Reference range: Expected values for healthy individuals as noted in the literature are typically $\leq 3$ mg/L

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

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

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