QUANTEX CRP HIGH SENSITIVITY STANDARD MULTIPOINT, QUANTEX CRP HIGH SENSITIVITY CONTROLS VE CONTROLS 1/2

K032663 · Instrumentation Laboratory CO · DCK · Dec 19, 2003 · Immunology

Device Facts

• Record ID: K032663
• Device Name: QUANTEX CRP HIGH SENSITIVITY STANDARD MULTIPOINT, QUANTEX CRP HIGH SENSITIVITY CONTROLS VE CONTROLS 1/2
• Applicant: Instrumentation Laboratory CO
• Product Code: DCK · Immunology
• Decision Date: Dec 19, 2003
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5270
• Device Class: Class 2

Intended Use

Quantex CRP High Sensitivity is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of C-Reactive Protein (CRP) in human serum on Clinical Chemistry Systems. C-Reactive Protein (CRP) aids in detecting and evaluating infection, tissue disorder, inflammatory disorders and associated diseases. Quantex CRP High Sensitivity standard multipoint is intended for use in establishing the calibration for the quantex CRP High Sensitivity reagents by turbidimetry. Quantex CRP High Sensitivity controls 1/2 are intended for use in monitoring the quality control of results obtained with quantex CRP High Sensitivity reagents by turbidimetry.

Device Story

Latex particle enhanced immunoturbidimetric assay; measures CRP in human serum. Sample mixed with latex reagent and reaction buffer; coated latex particles agglutinate in presence of CRP. Agglutination degree proportional to CRP concentration; measured via decrease in transmitted light. Used on ILab 600/900/1800 clinical chemistry systems. Provides quantitative CRP levels to assist clinicians in diagnosing/monitoring inflammatory conditions and infections.

Clinical Evidence

Method comparison study performed on 211 total samples (156 on ILab 900/1800; 55 on ILab 600) ranging from 0.18 to 283 mg/L. Correlation coefficients (r) were 0.9969 and 0.9989 respectively. Precision studies conducted using two control levels; within-run CV% ranged from 0.88% to 2.11%; total CV% ranged from 1.50% to 3.32%.

Technological Characteristics

Latex particle enhanced immunoturbidimetric assay. Reagents: polystyrene latex particles coated with rabbit polyclonal anti-CRP antibody, HEPES buffer, bovine serum albumin, sodium azide. Measures light transmission decrease at 660 nm. Compatible with ILab 600/900/1800 systems. Refrigerated storage (2-8°C).

Indications for Use

Indicated for quantitative determination of C-Reactive Protein (CRP) in human serum to aid in detecting and evaluating infection, tissue disorder, inflammatory disorders, and associated diseases.

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

• N High Sensitivity CRP (K991385)

Submission Summary (Full Text)

{0}

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

A. 510(k) Number:
k032663

B. Analyte:
C-reactive protein

C. Type of Test:
Quantitative Immunoturbidimetric Latex Agglutination

D. Applicant:
INSTRUMENTATION LABORATORY CO.

E. Proprietary and Established Names:
QUANTEX CRP HIGH SENSITIVITY, QUANTEX CRP HIGH SENSITIVITY STANDARD MULTIPOINT, QUANTEX CRP HIGH SENSITIVITY CONTROLS 1/2

F. Regulatory Information:
1. Regulation section:
21CFR §866.5270 - C-reactive protein immunological test system.
21CFR§862.1150 - Calibrator, primary
21CFR§862.1660 - Single analyte controls (assayed and unassayed)
2. Classification:
2, 2, 1
3. Product Code:
DCK, JIS, JJX
4. Panel:
Immunology (82), Chemistry (75)

G. Intended Use:
1. Indication(s) for use:
Quantex CRP High Sensitivity is intended as a latex particle enhanced immunoturbidimetric assay for the quantitative determination of C-Reactive Protein (CRP) in human serum on Clinical Chemistry Systems. C-Reactive

{1}

Page 2 of 6

Protein (CRP) aids in detecting and evaluating infection, tissue disorder, inflammatory disorders and associated diseases.

Quantex CRP High Sensitivity standard multipoint is intended for use in establishing the calibration for the quantex CRP High Sensitivity reagents by turbidimetry.

Quantex CRP High Sensitivity controls 1/2 are intended for use in monitoring the quality control of results obtained with quantex CRP High Sensitivity reagents by turbidimetry.

2. Special condition for use statement(s): Not Applicable

3. Special instrument Requirements: ILab 900/1800 and ILab 600

H. Device Description:

When a sample containing CRP is mixed with the Latex Reagent and the Reaction Buffer included in the kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of CRP in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates. C-Reactive Protein (CRP) aids in detecting and evaluating infection, tissue disorder, inflammatory disorders and associated diseases.

I. Substantial Equivalence Information:

1. Predicate device name(s): Dade Behring, N High Sensitivity CRP Assay (Predicate)

2. Predicate K number(s): K991385

3. Comparison with predicate:

{2}

Page 3 of 6

| Table of Comparison to Predicate Device | |
| --- | --- |
| quantex CRP High Sensitivity | N High Sensitivity CRP Assay (Predicate) |
| Manufacturer: | |
| Biokit SA in Barcelona, Spain | Dade Behring in Marburg, Germany |
| Intended Use: | |
| Quantitative in vitro diagnostic determination of C-reactive protein | Same |
| Sample Type: | |
| Serum | Serum, Heparin and EDTA plasma |
| Methodology: | |
| Particle Enhanced Immunoturbidimetry | Particle Enhanced Immunonephelometry |
| Test Principle: | |
| When a serum containing CRP is mixed with the Latex Reagent and the Reaction Buffer included in the kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of CRP in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates. | Polystyrene particles coated with monoclonal antibodies to CRP are agglutinated when mixed with samples containing CRP. The intensity of the scattered light in the nephelometer depends on the CRP content of the sample and therefore the CRP concentration can be determined versus dilutions of a standard of a known concentration. |
| Storage Conditions: | |
| Refrigerate at 2-8°C until expired | Same |
| Reagent Compositions: | |
| • Latex Reagent (ready-for-use) | N High Sensitivity CRP Reagent (ready-for-use) |
| Suspension of polystyrene latex particles coated with rabbit polyclonal antibody directed against human CRP containing bovine serum albumin, buffer and < 0.1% sodium azide. | Suspension of polystyrene particles coated with mouse monoclonal antibodies to CRP. Preservatives Gentamincin (6.25 mg/L) and Amphotericin (0.625 mg/L). |
| • Reaction Buffer (ready-for-use) | No equivalent reagent |
| HEPES buffer containing bovine serum albumin, IgG from normal rabbit and < 0.1% sodium azide. | |
| • quantex CRP High Sensitivity standard multipoint | N Rheumatology Standard SL (ready-for-use) |
| • (ready-for-use)* | |
| Diluted normal human serum in physiological saline solution containing human CRP at 5 different levels, stabilizer and < 0.1% sodium azide. | Mixture of human sera with elevated concentration of ASL, CRP and RF. Less than 1 g/L sodium azide. |
| • quantex CRP High Sensitivity controls 1/2 (ready-for-use)* | N/T Rheumatology Controls SL (ready-for-use) |
| Diluted normal human serum in physiological saline solution containing human CRP at 2 different levels, stabilizer and < 0.1% sodium azide. | Mixture of human sera with elevated concentration of ASL, CRP and RF with the additive pyrrolidine (approx. 50 g/l). |
| * sold separately | |

J. Standard/Guidance Document Referenced (if applicable):

None referenced

{3}

# K. Test Principle:

The quantex CRP High Sensitivity is a latex particle enhanced immunoturbidimetric assay to quantify CRP in serum. When a sample containing CRP is mixed with the Latex Reagent and the Reaction Buffer included in the kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of CRP in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates.

# L. Performance Characteristics (if/when applicable):

# 1. Analytical performance:

a. Precision/Reproducibility:

| ILab 600 | Replicates/ Runs | Mean (mg/L) | CV (%) | Replicates/ Runs | Mean (mg/L) | CV (%) |
| --- | --- | --- | --- | --- | --- | --- |
| Within run | 6/10 | 2.32 | 2.11 | 6/10 | 5.82 | 1.96 |
| Total | 6/10 | 2.32 | 2.50 | 6/10 | 5.82 | 2.09 |
| ILab 900/1800 | Replicates/ Runs | Mean (mg/L) | CV (%) | Replicates/ Runs | Mean (mg/L) | CV (%) |
| Within run | 6/12 | 2.39 | 1.25 | 6/12 | 5.87 | 0.88 |
| Total | 6/12 | 2.39 | 3.32 | 6/12 | 5.87 | 1.50 |

b. Linearity/assay reportable range:

ILab 600: 0.25 to $20.0\mathrm{mg / L}$ without the ILab automatic rerun capability. 0.10 to $400\mathrm{mg / L}$ with the ILab automatic rerun capability.

ILab 900/1800: 0.35 to $20.0\mathrm{mg / L}$ without the ILab automatic rerun capability. 0.10 to $100\mathrm{mg / L}$ with the ILab automatic rerun capability.

If the linear range is exceeded after the automatic rerun, dilute the sample 1:51 with saline, re-assay and correct the result for the dilution.

The assay does not show prozone effect (i.e. antigen excess) up to $400\mathrm{mg / L}$ .

c. Traceability (controls, calibrators, or method):

The reported values were determined over multiple runs against a Calibration House Standard which is traceable to the current Certified Reference Material for human serum proteins from the Institute for Reference Materials and Measurements (IRMM)

d. Detection limit:

The detection limit of this assay is

- ILab 600: $0.139\mathrm{mg / L}$ (rerun disabled); $0.046\mathrm{mg / L}$ (rerun enabled)
- ILab 900/1800: $0.145\mathrm{mg / L}$ (rerun disabled); $0.081\mathrm{mg / L}$ (rerun enabled)

{4}

Page 5 of 6

Lowest measurable CRP value with CV &lt; 15%:

- ILab 600: 0.25 mg/L (rerun disabled); 0.10 mg/L (rerun enabled)
- ILab 900/1800: 0.35 mg/L (rerun disabled); 0.10 mg/L (rerun enabled)

e. Analytical specificity:

No significant interference from triglyceride up to 1327 mg/dL, bilirubin up to 18.3 mg/dL (311.1 μmol/L), hemoglobin up to 490 mg/dL (0.294 mmol/L), Rheumatoid Factor up to 970 IU/mL and turbidity up to a sample absorbance of 2.39 AU/cm at 660 nm.

f. Assay cut-off:

Not Applicable

2. Comparison studies:

a. Method comparison with predicate device:

In method comparison studies evaluating 156 samples with CRP levels ranging from 0.18 to 283 mg/L on an ILab 900/1800 and 55 samples ranging from 0.20 to 283 mg/L on an ILab 600, the slope and correlation coefficient (r) for quantex CRP High Sensitivity versus the predicate device are shown below:

| IL System | Slope | Intercept | | r |
| --- | --- | --- | --- | --- |
| ILab 900/1800 | 0.948 | -0.105 | | 0.9969 |
| ILab 600 | 0.957 | -0.074 | | 0.9989 |

b. Matrix comparison:

Not Applicable

3. Clinical studies:

a. Clinical sensitivity:

Not Applicable

b. Clinical specificity:

Not Applicable

4. Clinical cut-off:

Not Applicable

5. Expected values/Reference range:

A normal range study (51 Men / 68 Women; age range: 19-66) was performed using quantex CRP High Sensitivity on an ILab 900 instrument. The upper limit of the normal range, calculated as recommended by the International Federation of Clinical Chemistry (IFCC), was 5.6 mg/L (n=119), which agreed with already published values for adult population.

Due to many variables which may affect results, each laboratory should establish its own normal range. A CRP value within the normal range does not exclude tissue damage.

{5}

Page 6 of 6

## M. Conclusion:

The information and data provided by INSTRUMENTATION LABORATORY CO. supports a Substantial Equivalence (SE) determination of QUANTEX CRP HIGH SENSITIVITY, QUANTEX CRP HIGH SENSITIVITY STANDARD MULTIPOINT, QUANTEX CRP HIGH SENSITIVITY CONTROLS 1/2 to other C-REACTIVE PROTEIN, ANTIGEN, ANTISERUM, AND CONTROL regulated under 21 CFR §866.5270 - C-reactive protein immunological test system.