C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS
Device Facts
| Record ID | K053603 |
|---|---|
| Device Name | C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR COBAS INTEGRA INSTRUMENTS |
| Applicant | Roche Diagnostics Corp. |
| Product Code | NQD · Immunology |
| Decision Date | Feb 9, 2006 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.5270 |
| Device Class | Class 2 |
Indications for Use
The CRP (Latex) High Sensitive Immunoturbidimetric assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on Roche automated clinical chemistry analyzers. Measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. Highly sensitive measurement of CRP may also be used as an aid in the assessment of the risk of future coronary heart disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome.
Device Story
The CRP (Latex) HS Test System is an in vitro diagnostic assay for human serum or plasma. It utilizes latex particle-enhanced immunoturbidimetry; monoclonal anti-CRP antibodies coated on latex microparticles agglutinate in the presence of CRP. The resulting precipitate is measured turbidimetrically on Roche automated clinical chemistry analyzers (Integra 400, 400 plus, 700, 800). The system provides quantitative CRP concentrations. It is used in clinical laboratory settings by trained technicians. Results assist clinicians in evaluating inflammatory states, infection, tissue injury, and cardiovascular risk assessment. The device benefits patients by providing high-sensitivity CRP measurements to aid in coronary heart disease risk stratification and prognosis for acute coronary syndromes.
Clinical Evidence
Bench testing only. Method comparison performed against predicate devices (K042485 and K033908). Passing-Bablok regression analysis (y=1.0548x + 0.0424; r=0.996) demonstrated correlation. Precision evaluated via within-run and between-run CVs; within-run CVs ranged 0.6-1.3%, between-run CVs 2.2-3.5%. Functional sensitivity (CV <10%) reported at 0.3 mg/L. Interference testing confirmed no significant interference from bilirubin, hemoglobin, triglycerides, or rheumatoid factors up to specified limits.
Technological Characteristics
Latex particle-enhanced immunoturbidimetric assay. Reagents: R1 (TRIS buffer, BSA, mouse immunoglobulins, stabilizers) and R2 (latex particles coated with mouse anti-CRP antibodies in glycine buffer). Standardized to CRM 470. Measuring range 0-20 mg/L (up to 300 mg/L with dilution). Automated analysis on COBAS Integra systems. No high-dose hook effect up to 1000 mg/L.
Indications for Use
Indicated for in vitro quantitative determination of CRP in human serum and plasma to detect/evaluate inflammatory disorders, infection, and tissue injury; also used as an aid in assessing future coronary heart disease risk and as an adjunct indicator for recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome.
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
Related Devices
- K081294 — ADVIA CHEMISTRY CARDIOPHASE HIGH SENSITIVITY C-REACTIVE PROTEIN (HSCRP), CALIBRATORS · Siemens Healthcare Diagnostics, Inc. · Jul 29, 2008
- K073277 — ROCHE-CREACTIVE PROTEIN (LATEX) · Roche Diagnostics Corp. · Mar 6, 2008
Submission Summary (Full Text)
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE
A. 510(k) Number:
K053603
B. Purpose for Submission:
New assay
C. Measurand:
C-Reactive Protein
D. Type of Test:
Particle enhanced turbidimetric assay.
E. Applicant:
ROCHE DIAGNOSTICS CORP.
F. Proprietary and Established Names:
C-REACTIVE PROTEIN (LATEX) HIGH SENSITIVE TEST SYSTEM FOR
COBAS INTEGRA INSTRUMENTS
G. Regulatory Information:
1. Regulation section:
21CFR Sec- 866.5270-C-reactive protein immunological test system.
2. Classification:
2
3. Product code:
NQD - CARDIAC C-REACTIVE PROTEIN, ANTIGEN, ANTISERUM, AND
CONTROL
4. Panel:
Immunology (82)
H. Intended Use:
1. Intended use(s):
The CRP (Latex) High Sensitive Immunoturbidimetric assay is for the in vitro
quantitative determination of C-reactive protein (CRP) in human serum and
plasma on Roche automated clinical chemistry analyzers. Measurement of CRP is
of use for the detection and evaluation of inflammatory disorders and associated
diseases, infection and tissue injury. Highly sensitive measurement of CRP may
also be used as an aid in the assessment of the risk of future coronary heart
disease. When used as an adjunct to other laboratory evaluation methods of acute
coronary syndromes, it may also be an additional independent indicator of
recurrent event prognosis in patients with stable coronary disease or acute
coronary syndrome.
2. Indication(s) for use:
The CRP (Latex) High Sensitive Immunoturbidimetric assay is for the in vitro
quantitative determination of C-reactive protein (CRP) in human serum and
plasma on Roche automated clinical chemistry analyzers. Measurement of CRP is
of use for the detection and evaluation of inflammatory disorders and associated
diseases, infection and tissue injury. Highly sensitive measurement of CRP may
also be used as an aid in the assessment of the risk of future coronary heart
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disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome.
3. Special conditions for use statement(s):
Prescription use
4. Special instrument requirements:
The CRP (Latex) HS assay is intended for use on Roche automated clinical chemistry analyzers.
This submission describes applications for the Integra family of analyzers; namely, the Integra 400, 400 plus, 700, and 800. The Integra family of analyzers is cleared under K951595.
I. Device Description:
The CRP (latex) HS Test System is a latex particle-enhanced immunoturbidimetric test for the quantitative measurement of C-reactive protein in human serum or plasma. Human CRP agglutinates with latex particles coated with monoclonal anti-CRP antibodies. The precipitate is determined turbidimetrically. The calibrator is the Calibrator for automated systems (C.f.a.s). Proteins; and the recommended control materials are CRP T Control N and Precinorm Protein. The reagents are for use on the Integra 400, 400 plus, 700 and 800 analyzers.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Roche Tina-quant® CRP (latex) HS Test System, Dade Behring N High Sensitivity CRP
2. Predicate 510(k) number(s):
K042485, K033908 respectively
3. Comparison with predicate:
The CRP (latex) HS Test System for COBAS Integra instruments is compared to the currently marketed Roche Tina-quant® CRP (latex) HS Test System cleared under K042485. For purposes of cardiac risk assessment, the CRP (latex) HS system is also equivalent to the Dade Behring N High Sensitivity CRP (K033908)
The Tina-quant® CRP (Latex) High Sensitive Immunoturbidimetric assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on Roche automated clinical chemistry analyzers. Highly sensitive measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. Measurement of CRP may also be used as an aid in the assessment of the risk of future coronary heart disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome.
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Both test systems are intended for the in vitro quantitative determination of C-reactive protein in human serum and plasma and have the same indications for use. Both share the same test principle - they are both latex-particle enhanced immunoturbidimetric assays. The reagents are quite similar; the active ingredients and antibodies are the same. Both are ultimately traceable to the same reference material (CRM 470).
The new test system has similar imprecision, known interferences, comparable standards and calibrators, and is comparable in absolute values to the predicate device. They share expected values and instructions for result interpretation.
This test system is intended for use on the COBAS Integra family of analyzers while the predicate device was intended for use on the Roche/Hitachi family of analyzers. There are some very minor differences in reagent composition.
Compared to the predicate device, this test system has some slight differences in specific performance characteristics.
## K. Standard/Guidance Document Referenced (if applicable):
Guidance for Industry - Review Criteria for Assessment of C- Reactive Protein (CRP), High Sensitivity C-Reactive Protein (hsCRP) and Cardiac C-Reactive Protein (cCRP) Assays: http://www.fda.gov/cdrh/oivd/guidance/1246.html
## L. Test Principle:
The Immunoturbidimetric methodology used in this assay is well-established and is the basis for the already cleared Integra CRP assay (K981897). During the reaction, anti-CRP antibodies coupled with latex microparticles react with CRP in the sample to form an antigen-antibody agglutinate, which is measured turbidimetrically.
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
Reproducibility was determined using human samples and controls (within run n = 21, between run n = 21).
| Sample | Within-run | | Between-run | |
| --- | --- | --- | --- | --- |
| | Mean mg/L (nmol/L) | CV % | Mean mg/L (nmol/L) | CV % |
| Control Level 1 | 3.3 (31.4) | 0.9 | 3.3 (31.4) | 3.5 |
| Control Level 2 | 8.0 (76.2) | 0.7 | 8.0 (76.2) | 2.2 |
| Human pool 1 | 1.6 (15.2) | 1.3 | 1.5 (14.3) | 3.1 |
| Human pool 2 | 11.4 (109) | 0.6 | 11.4 (109) | 2.3 |
#### b. Linearity/assay reportable range:
To determine linearity of the CRP (Latex) HS test system, three dilution series of different analyte concentrations were measured as samples using the CRP (Latex) Test system on the Integra 700. The three dilution series covered the low end (0-3 mg/L); midrange (0-30mg/L) and extended measuring ranges (0-
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306mg/L). The attached files show the results of these measurements. The linearity data support a linear range of 0 up to 306 mg/L. Comparable results were found on the Integra 400
c. Traceability, Stability, Expected values (controls, calibrators, or methods): The calibrators and controls including stability claims have all been previously cleared and used with CRP test systems. Their composition has not been modified for use with the CRP (Latex) HS test system.
All calibrators and controls are traceable to the reference preparation CRM 470. All value assignments were performed under standardized conditions using CRP (Latex) HS reagents.
d. Detection limit:
**Analytical sensitivity (lower detection limit)**
0.1 mg/L (0.952 nmol/L)
The detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying three standard deviations above that of a zero sample (zero sample + 3 SD, within run precision, n = 21).
**Functional sensitivity (limit of quantitation)**
0.3 mg/L (2.96 nmol/L)
The functional sensitivity (limit of quantitation) is the lowest CRP concentration that can be reproducibly measured with an inter-assay coefficient of variation of <10%.
e. Analytical specificity:
Interference
Criterion: Recovery within ±10% of initial value.
Serum, plasma
Hemolysis - No interference up to 10 g/L or 621 μmol/L hemoglobin.
Icterus - No interference up to 0.6 g/L or 1030 μmol/L bilirubin.
Lipemia(Intralipid) - No significant interference up to a triglycerides level of 5 g/L at 2 mg/L or 19 nmol/L CRP.
High-dose hook effect - Does not occur at CRP concentrations below 40 mg/L or 380 nmol/L. Samples with concentrations >40 mg/L are flagged either >TEST RNG or "HIGH ACT".
Rheumatoid factors - No interference up to 1200 IU/mL.
Dysproteinemia - In very rare cases, monoclonal gammopathy may lead to false CRP values due to formation of turbidity or direct interaction of the monoclonal antibody in the specimen with the test system.
HAMA - Although measures were taken to minimize interference caused by human anti-mouse antibodies, erroneous findings may be obtained from samples taken from patients who have been treated with monoclonal mouse antibodies or have received them for diagnostic purposes.
f. Assay cut-off:
Not Applicable
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2. Comparison studies:
a. Method comparison with predicate device:
Method comparison
CRP values for human serum and plasma samples obtained on a COBAS INTEGRA 700 analyzer with the COBAS INTEGRA C-Reactive Protein (Latex) cassette High Sensitive Assay (CRPHS) were compared to two commercially available alternative automated systems. Sample size (n) represents all replicates.
Roche Tina-quant® CRP (latex) HS Test System:
Values ranged from 0.2 to 16.3 mg/L (1.9 to 15.5 nmol/L).
Passing/Bablok30 Linear regression
$$y = 1.0548x + 0.0414y = 0.9877x + 0.1264$$
$$\tau = 0.956 \quad r = 0.996$$
Number of samples measured: 58
Dade Behring N High Sensitivity CRP:
Values ranged from 0.1 to 9.0 mg/L (1.0 to 8.6 nmol/L).
Passing/Bablok30 Linear regression
$$y = 0.9715x + 0.0211y = 0.9941x + 0.0295$$
$$\tau = 0.935 \quad r = 0.998$$
Number of samples measured: 54
b. Matrix comparison:
The studies described in this submission were all performed using serum samples. To validate the use of the additional sample types Li-heparin and K2-EDTA plasma with the CRP (Latex) HS assay; parallel samples were collected in serum, Li-heparin plasma, and K2-EDTA collection tubes and analyzed on the Integra 700 analyzer using the CRP(Latex) HS test system. The serum sample was used as the reference sample and for each plasma tube type, the deviation from the reference sample was noted. For samples < 1 mg/L CRP, the deviation was expressed in absolute terms; and for samples > 1 mg/L CRP the deviation was expressed as a percentage. The plasma sample types were considered acceptable if the average deviation for samples < 1 mg/L was < 0.1 mg/L; or 10% for samples > 1 mg/L. As can be seen by the attached data, these criteria were met, supporting the method sheet recommendation of Li-heparin and K2-EDTA plasma as acceptable specimen types.
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:
Consensus reference interval for adults:
<5.0 mg/L
IFCC/CRM 470
The CDC/AHA recommended the following hsCRP cut-off points (tertiles) for CVD risk assessment:
<1.0 mg/L low
1.0–3.0 mg/L average
>3.0 mg/L high
Patients with higher hsCRP concentrations are more likely to develop myocardial infarction and severe peripheral vascular disease.
Pearson TA et al. Markers of Inflammation and Cardiovascular Disease.
Application to Clinical and Public Health Practice. A Statement for Healthcare Professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-511.
5-95% reference intervals of neonates and children:
Neonates (0-3 weeks): 0.1-4.1 mg/L
Children (2 months-15 years): 0.1-2.8 mg/L
Schlebusch H, Liappis N, Kalina E, Klein G. High Sensitive CRP and Creatinine: Reference Intervals from Infancy to Childhood. J Lab Med 2002;26:341-346.
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.
