CHOLETECH LDX HIGH-SENSITIVITY C-REACTIVE PROTEIN (HS-CRP)
Device Facts
| Record ID | K040579 |
|---|---|
| Device Name | CHOLETECH LDX HIGH-SENSITIVITY C-REACTIVE PROTEIN (HS-CRP) |
| Applicant | Cholestech Corp. |
| Product Code | DCK · Immunology |
| Decision Date | Jun 18, 2004 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.5270 |
| Device Class | Class 2 |
Indications for Use
Cholestech LDX high sensitivity C-Reactive Protein (hs-CRP) is an in vitro diagnostic test for the quantitative determination of CRP in whole blood or serum. Measurement of CRP is useful as an aid in the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases.
Device Story
System uses lateral flow immunoassay with colloidal gold-coated monoclonal antibodies to measure CRP levels. Input: whole blood (fingerstick/venous) or serum applied to disposable cassette. Cassette contains internal mechanism to separate plasma from blood cells. Analyzer uses reflectance photometry to measure reaction color. Calibration data stored on magnetic stripe on each cassette, read by analyzer upon insertion. Used in point-of-care settings by professionals. Output: CRP concentration in mg/L displayed to clinician. Results assist in clinical evaluation of inflammatory states and tissue injury.
Clinical Evidence
Bench testing only. Precision evaluated per NCCLS EP5-A; total CVs ranged from 11.4% to 14.3% for controls and 6.6% to 17.4% for whole blood. Linearity established for 0.3–10 mg/L (whole blood) and 0.3–8 mg/L (serum). Method comparison with nephelometric reference (n=72) showed slope 1.02, intercept 0.21, r=0.976. Matrix comparison (n=78) between serum and whole blood showed high correlation (r=0.977–0.982). Analytical specificity tested against 14 common substances with <10% interference.
Technological Characteristics
Lateral flow immunoassay; colloidal gold particles coated with monoclonal antibodies; reflectance spectrophotometry detection. Dimensions: desk-top analyzer. Connectivity: magnetic stripe reader for calibration. Sample: whole blood or serum. Software: embedded firmware for reflectance-to-concentration conversion.
Indications for Use
Indicated for the quantitative determination of C-reactive protein (CRP) in whole blood or serum to aid in the detection and evaluation of infection, tissue injury, inflammatory disorders, and associated diseases in patients.
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 N High Sensitivity CRP assay on the BN100 (K991385)
Related Devices
- K121558 — DIAZYME HSCRP POC TEST KIT · Diazyme Laboratories · Sep 21, 2012
- K022690 — PAROS CRP · Horiba, Ltd. · Dec 23, 2002
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE
A. 510(k) Number:
k040579
B. Purpose for Submission:
Seeking 510(K) clearance for a new device
C. Analyte:
C-reactive protein
D. Type of Test:
Quantitative
E. Applicant:
CHOLESTECH CORP.
F. Proprietary and Established Names:
CHOLESTECH LDX HIGH-SENSITIVITY C-REACTIVE PROTEIN (HS-CRP)
G. Regulatory Information:
1. Regulation section:
21CFR §866.5270 -C-reactive protein immunological test system.
2. Classification:
Class 2
3. Product Code:
DCK
4. Panel:
Immunology (82)
H. Intended Use:
1. Indication(s) for use:
Cholestech LDX high sensitivity C-Reactive Protein (hs-CRP) is an in vitro diagnostic test for the Quantitative determination of CRP in whole blood or serum.
Measurement of CRP is useful as an aid in the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases.
2. Special condition for use statement(s):
Prescription Use
3. Special instrument Requirements:
Cholestech LDX Analyzer (k901900)
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# I. Device Description:
The Cholestech LDX System is a desk-top analyzer that utilizes dry chemistry cassettes and reflectance photometry to quantify substances in blood. Samples used for testing can be whole blood from a fingerstick (collected in a lithium heparin coated capillary tube), serum, or anticoagulated whole blood collected by venipuncture. The 50 μl sample is applied to a Cholestech LDX hs-CRP cassette. The cassette is then placed into the Cholestech LDX Analyzer where a unique system on the cassette separates the plasma from the blood cells. Plasma is then incubated with a colloidal gold anti-CRP conjugate. A lateral flow system transfers the gold conjugate through an anti-CRP antibody capture zone. Gold conjugate containing CRP is captured by the antibody while the rest of the gold conjugate is washed away. The signal in the capture zone is measured by the Cholestech LDX Analyzer. A brown (magnetic) stripe on each cassette contains the calibration information required for the Cholestech LDX Analyzer to convert the reflectance reading (% R) to hs-CRP concentration in mg/L.
# J. Substantial Equivalence Information:
1. Predicate device name(s): Dade Behring N High Sensitivity CRP
2. Predicate K number(s): k991385
3. Comparison with predicate:
| Cholestech LDX hs-CRP vs Dade Behring BN100 high sensitivity CRP | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Indications for Use | Reactive Protein (hs-CRP) test is an in vitro diagnostic test for the quantitative determination of C-reactive protein (CRP) in whole blood or serum. Measurement of CRP is useful as an aid in the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases. | N High Sensitivity CRP is an in vitro diagnostic assay intended 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, are observed. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory disorders and associated diseases |
| Instrument Required | LDX Analyzer | Dade Behring BN-100 Nephelometer |
| Technology | Lateral flow immunoassay utilizing colloidal gold particles coated with monoclonal | Agglutination of polystyrene particles coated with monoclonal antibodies detected by nephelometry |
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| | antibodies detected by reflectance spectrophotometry. | |
| --- | --- | --- |
| Assay Range | 0.2 to 10 mg/L | 0.175 to 11 mg/L
up to 1100 mg/dL with sample dilution |
| Sample Type | Whole blood (capillary and venous) and serum | Serum or plasma |
| Cholestech LDX hs-CRP vs Dade Behring BN100 high sensitivity CRP | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Calibration Requirements | No calibration performed by the user test information is encoded the magnetic stripe of the cassette and the stripe is read by the LDX Analyzer each time a cassette is run | Calibration required via the use of the N CRP Standard SY; under typical operating conditions, the HS-CRP reagents must be calibrated every 4 weeks, and also with certain parts replacement or maintenance procedures |
| Testing Environment | Professional-Use, point-of-care | Professional-Use, conventional laboratory |
## K. Standard/Guidance Document Referenced (if applicable):
NCCLS protocol EP5-A, Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline (1998)
## L. Test Principle:
Lateral flow immunoassay utilizing colloidal gold particles coated with monoclonal antibodies detected by reflectance spectrophotometry
## M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
A study was conducted according to NCCLS protocol EP5-A, Evaluation of Precision Performance of Clinical Chemistry Devices; Approved Guideline (1998).
hs-CRP
| | Control Material Level 1 | Control Material Level 2 | Serum Pool |
| --- | --- | --- | --- |
| X (mg/L) = | 1.20 | 2.94 | 6.51 |
| Within run | | | |
| %CV= | 12.1% | 11.7% | 8.7% |
| Total %CV= | 14.3% | 11.5% | 11.4% |
Whole Blood
Within-run Precision
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| | Level 1 | Level 2 | Level 3 | Level 4 |
| --- | --- | --- | --- | --- |
| X (mg/L) = 0.60 | 1.22 | 2.89 | 4.85 | |
| SD (mg/L) = 0.09 | 0.21 | 0.33 | 0.32 | |
| %CV = 15.2% | 17.4% | 11.5% | 6.6% | |
b. Linearity/assay reportable range:
The reportable range for hs-CRP using whole blood or capillary blood from fingerstick is $0.3 - 10\mathrm{mg / L}$ . Results outside this range will appear as $< 0.3$ or $>10$ . The reportable range for hs-CRP using serum is $0.3 - 8\mathrm{mg / L}$ . Results outside this range will appear as $< 0.3$ or $>8$ . The reportable ranges are based on Linearity Studies and Deming regression correlation adjustments for sample matrix.
c. Traceability (controls, calibrators, or method):
Calibration is traceable to the predicate device. The calibration curve is encoded on the brown magnetic stripe of the cassette. The magnetic stripe is read by the Cholestech LDX each time a cassette is run.
d. Detection limit:
The limit of detection $(0.3\mathrm{mg / L})$ is based on the functional sensitivity of the assay which is defined as the concentration of CRP that results in a $20\%$ Coefficient of Variation (CV).
e. Analytical specificity:
The substances listed below were tested for interference with the hs-CRP test. Less than $10\%$ interference was seen at the levels shown.
| Substance Concentration | (mg/dL) |
| --- | --- |
| Triglycerides | 3000 |
| Bilirubin (unconjugated) | 20 |
| Ditauro Bilirubin | 20 |
| Hemoglobin | 120 |
| Lactate | 100 |
| Glucose | 1200 |
| Ascorbic Acid | 3 |
| Uric Acid | 20 |
| Urea | 500 |
| Creatinine | 30 |
| Potassium | 10 mmol/L |
| Protein (total) | 9 g/dL |
| Protein (albumin) | 7 g/dL |
| Protein (gamma globulin) | 6 g/dL |
f. Assay cut-off:
Not Applicable
2. Comparison studies:
a. Method comparison with predicate device:
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A comparison with a nephelometric method using 72 samples was performed. The following linear regression equation was obtained:
$$
X = \text{Nephelometric Reference Method (serum)}
$$
$$
Y = \text{Cholestech LDX Analyzer}
$$
| Sample Type | No. of Pairs | Slope | y Intercept | Correlation coefficient | Range of Values |
| --- | --- | --- | --- | --- | --- |
| LDX | 72 | 1.02 | 0.21 | 0.976 | 0.17-7.18 |
| Serum | | | | | |
b. Matrix comparison:
Comparison studies between serum and venous whole blood and between serum and fingerstick whole blood, using 78 samples, were performed. The following linear regressions were obtained:
| Sample Type | No. of Pairs | Slope | y Intercept | Correlation coefficient | Range of Values |
| --- | --- | --- | --- | --- | --- |
| LDX | 78 | 1.06 | 0.07 | 0.977 | 0.17-8.75 |
| Venous Whole Blood | 78 | 1.08 | 0.00 | 0.982 | 0.17-8.75 |
| Fingerstick | 78 | 1.08 | 0.00 | 0.982 | 0.17-8.75 |
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
4. Clinical cut-off: Not Applicable
5. Expected values/Reference range:
From published literature
Hs-CRP values range between 0.3 and 8.6 mg/L in healthy men and between 0.2 and 9.1 mg/L in healthy women who are not taking hormone replacement therapy. ¹ Hs-CRP values > 8 mg/L observed in an apparently healthy individual should be repeated in order to help rule out a recent response to undetected infection or tissue injury. ²
N. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
¹ Clinical Chemistry 2003; 49:8, 1258-71
² Circulation 2003; 107(3), 499-511
