In vitro test for the quantitative determination of C-reactive protein in human serum and plasma on the cobas c 111 system.
Particle enhanced turbidimetric assay
Human CRP agglutinates with latex particles coated with monoclonal anti-CRP antibodies. The precipitate is determined turbidimetrically.
1‑200 mg/L (0.1‑20 mg/dL)
Determine samples having higher concentrations via the rerun function. Dilution of samples via the rerun function is a 1:10 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 10.
Lower detection limit of the test:
1.0 mg/L (0.1 mg/dL)
The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 3 standard deviations above that of the lowest standard (standard 1 + 3 SD, repeatability, n = 21).
Adults LREFSchumann G, Dati F. Vorläufige Referenzbereiche für 14 Proteine im Serum (für Erwachsene) nach Standardisierung immunchemischer Methoden unter Bezug auf das internationale Referenzmaterial CRM 470. Lab Med 1995;19:401-403. | < 5 mg/L | (< 0.5 mg/dL) | |
Newborns LREFSchlebusch H, Liappis N, Kalina E, et al. High Sensitive CRP and Creatinine: Reference Intervals from Infancy to Childhood. J Lab Med 2002;26:341-346. | 0 days | < 0.6 mg/L | (< 0.06 mg/dL) |
Roche has not evaluated reference ranges in a pediatric population.
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Criterion: Recovery within ± 10 % of initial value at a CRP concentration of < 5 mg/L (MDL).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Rheumatoid factors up to 1200 IU/mL do not interfere.
High dose hook‑effect: No false result occurs up to a CRP concentration of 3100 mg/L.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on the cobas c 111 analyzer. For information about test combinations requiring special wash steps, please refer to the latest version of the carry over evasion list found with the CLEAN Method Sheet and the operator’s manual for further instructions.
Where required, special wash/carry-over evasion programming must be implemented prior to reporting results with this test.
|
| Analyzer(s) on which kit(s) can be used | |
05401615 190 | C-reactive protein (latex) (2 × 100 tests) | cobasc 111 | |
11355279 216 | C.f.a.s. Proteins (5 × 1 mL) | Code 656 | |
11355279 160 | C.f.a.s. Proteins (5 × 1 mL, for USA) | Code 656 | |
10557897 122 | Precinorm Protein (3 × 1 mL) | Code 302 | |
10557897 160 | Precinorm Protein (3 × 1 mL, for USA) | Code 302 | |
11333127 122 | Precipath Protein (3 × 1 mL) | Code 303 | |
11333127 160 | Precipath Protein (3 × 1 mL, for USA) | Code 303 | |
05117003 190 | PreciControl ClinChem Multi 1 (20 × 5 mL) | Code 391 | |
05947626 190 | PreciControl ClinChem Multi 1 (4 × 5 mL) | Code 391 | |
05947626 160 | PreciControl ClinChem Multi 1 (4 × 5 mL, for USA) | Code 391 | |
05117216 190 | PreciControl ClinChem Multi 2 (20 × 5 mL) | Code 392 | |
05947774 190 | PreciControl ClinChem Multi 2 (4 × 5 mL) | Code 392 | |
05947774 160 | PreciControl ClinChem Multi 2 (4 × 5 mL, for USA) | Code 392 | |
04774230 190 | NaCl Diluent 9 % | Code 951 | |
11930630 001 | Chimneys |
CRPLX: ACN 019
R1 | Ready for use. |
SR | Ready for use. |
Under conditions of extreme humidity, condensation may lead to a dilution of the reagent that affects the measurements. Hence under environmental conditions in which temperature and humidity are equal to, or in excess of 25 °C/80 %, 28 °C/70 %, 30 °C/60 % or 32 °C/55 % a chimney (Cat. No. 11930630 001) should be used to reduce the condensation rate. Place a white chimney in R1 and a black chimney in SR. The chimneys can be reused for reagent bottles within the same kit. However, to avoid contamination of the reagent with detergent or dilution of the reagent with water it is not permitted to wash the chimneys before reuse.
Measuring mode | Absorbance |
Abs. calculation mode | Kinetic |
Reaction direction | Increase |
Wavelength A | 552 nm |
Calc. first/last | 17/25 |
Antigen excess check | No |
Unit | mg/L |
Reaction mode | R1-S-SR |
Diluent (H2O) | ||
R1 | 82 µL | 48 µL |
Sample | 2.5 µL | 30 µL |
SR | 28 µL | 14 µL |
Total volume | 204.5 µL |
CRPLX | |
Shelf life at 2‑8 °C: | See expiration date on reagent |
On-board in use and refrigerated on the analyzer: | 5 weeks |
NaCl Diluent 9 % | |
Shelf life at 2‑8 °C: | See expiration date on reagent |
On-board in use and refrigerated on the analyzer: | 4 weeks |
Calibrator | Calibrator f.a.s. Proteins |
Calibration dilution ratio | 1:0.5, 1:1, 1:1.5, 1:2.86, 1:10 and 0 mg/L performed automatically by the instrument. Deionized water is used automatically by the instrument as the zero calibrator. |
Calibration mode | Linear interpolation |
Calibration interval | Each lot and as required following quality control procedures |
Enter the assigned lot-specific CRP value for all 6 calibrator points indicated in the package insert for Calibrator f.a.s. Proteins.
Traceability: This method has been standardized against the reference preparation of the IRMM (Institute for Reference Materials and Measurements) BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in Human Serum).
Representative performance data on the cobas c 111 analyzer are given below. Results obtained in individual laboratories may differ.
Precision was determined using human samples and controls in an internal protocol with repeatability (n = 21) and intermediate precision (3 aliquots per run, 1 run per day, 10 days). The following results were obtained:
Repeatability | Mean | SD | CV |
|---|---|---|---|
Precinorm Protein | 18.3 (1.83) | 0.2 (0.02) | 0.8 |
Precipath Protein | 37.7 (3.77) | 0.2 (0.02) | 0.6 |
Human serum 1 | 4.2 (0.42) | 0.1 (0.01) | 2.0 |
Human serum 2 | 23.4 (2.34) | 0.3 (0.03) | 1.3 |
Intermediate precision | Mean | SD | CV |
|---|---|---|---|
Precinorm Protein | 18.6 (1.86) | 0.4 (0.04) | 2.1 |
Precipath Protein | 38.4 (3.84) | 0.6 (0.06) | 1.6 |
Human serum 1 | 4.7 (0.47) | 0.1 (0.01) | 2.7 |
Human serum 2 | 23.3 (2.33) | 0.6 (0.06) | 2.6 |
CRP values for human serum and plasma samples obtained on the cobas c 111 analyzer using the Roche CRPLX reagent (y) were compared with those determined using the same reagent on a COBAS INTEGRA 400 analyzer (x).
Sample size (n) = 63
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.995x + 1.33 mg/L | y = 0.975x + 2.86 mg/L |
τ = 0.970 | r = 0.997 |
The sample concentrations were between 1.0 and 185 mg/L (0.1 and 18.5 mg/dL). |
Most tissue-damaging processes such as infections, inflammatory diseases and malignant neoplasms are associated with a major acute phase response of the C‑reactive protein (CRP) and other acute phase reactants (e.g. AAT, AAGP, C3C, C4, HAPT). The CRP response frequently precedes clinical symptoms, including fever. In normal healthy individuals CRP is a trace protein with a range up to 5 mg/L. After onset of an acute phase response the serum CRP concentration rises rapidly and extensively.
Alterations are detectable within 6 to 8 hours and the peak value is reached within 24 to 48 hours. Levels of up to thousandfold the normal value are associated with severe stimuli such as myocardial infarction, major trauma, surgery, or malignant neoplasms. CRP activates the classical complement pathway. CRP has a half-life of only a few hours, making it an ideal tool for clinical monitoring. Postoperative monitoring of CRP levels of patients indicates either the normal recovery process (decreasing levels to normal) or unexpected complications (persisting high levels). Measuring changes in the concentration of CRP provides useful diagnostic information about how acute and how serious a disease is. It also allows the assessment of complications during the disease and judgements about the disease genesis. Persistence of a high serum CRP concentration is usually a grave prognostic sign which generally indicates the presence of an uncontrolled infection. CRP determination may replace the classical determination of Erythrocytes Sedimentation Rate (ESR), due to its prompt response to changes in disease activity and its good correlation to ESR.
R1 | TRIS buffer with bovine serum albumin and immunoglobulins (mouse); preservative |
SR | Latex particles coated with anti-CRP (mouse) in glycine buffer; preservative |
For in vitro diagnostic use.
Exercise the normal precautions required for handling all laboratory reagents.
Disposal of all waste material should be in accordance with local guidelines.
Safety data sheet available for professional user on request.
For USA: For prescription use only.
For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.
The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.
Follow the applicable government regulations and local guidelines for quality control.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum: Separate immediately from clot and analyze promptly.
Plasma: Li-heparin, K3-EDTA plasma.
The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.
Centrifuge samples containing precipitates before performing the assay.
Stability: LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002. | 11 days at 15‑25 °C |
2 months at 2‑8 °C | |
3 years at (‑15)‑(‑25) °C |
In vitro test for the quantitative determination of C‑reactive protein in human serum and plasma on Roche/Hitachi cobas c systems.
Particle enhanced immunoturbidimetric assay.
Human CRP agglutinates with latex particles coated with monoclonal anti‑CRP antibodies. The precipitate is determined turbidimetrically.
Measuring range
1.00‑250 mg/L (9.52‑2380 nmol/L, 0.1‑25 mg/dL)
Determine samples having higher concentrations via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 3.
Lower limits of measurement
Lower detection limit of the test
1.00 mg/L (9.52 nmol/L, 0.1 mg/dL)
The lower 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 the lowest standard (standard 1 + 3 SD, repeatability, n = 21).
Adults LREFSchumann G, Dati F. Vorläufige Referenzbereiche für 14 Proteine im Serum (für Erwachsene) nach Standardisierung immunchemischer Methoden unter Bezug auf das internationale Referenzmaterial CRM 470. Lab Med 1995;19:401-403. | < 5 mg/L | (< 0.5 mg/dL) |
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Criterion: Recovery within ± 10 % of initial values at a CRP concentration of 5.0 mg/L (47.6 nmol/L, 0.5 mg/dL).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Rheumatoid factors up to 1200 IU/mL do not interfere.
High dose hook-effect: No false result occurs up to a CRP concentration of 1000 mg/L (9520 nmol/L, 100 mg/dL).
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Therapeutic drugs: Significantly decreased CRP values may be obtained from samples taken from patients who have been treated with carboxypenicillins.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
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.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on Roche/Hitachi cobas c systems. The latest version of the carry‑over evasion list can be found with the NaOHD/SMS/Multiclean/SCCS or the NaOHD/SMS/SmpCln1+2/SCCS Method Sheets. For further instructions refer to the operator’s manual.
Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.
Analyzer(s) on which cobas c pack(s) can be used | |||
20764930 322 | C-Reactive Protein (Latex) 300 tests | System‑ID 07 6493 0 | Roche/Hitachi cobas c 311, cobas c 501 |
11355279 216 | Calibrator f.a.s. Proteins (5 x 1 mL) | Code 656 | |
10557897 122 | Precinorm Protein (3 x 1 mL) | Code 302 | |
11333127 122 | Precipath Protein (3 x 1 mL) | Code 303 | |
05117003 190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | Code 391 | |
PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 391 | ||
05117216 190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | Code 392 | |
PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 392 | ||
04489357 190 | Diluent NaCl 9 % (50 mL) | System‑ID 07 6869 3 |
CRPLX: ACN 019
Ready for use
Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.
Mix cobas c pack well before placing on the analyzer.
cobas c 311 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 7‑18 | ||
Wavelength (sub/main) | –/546 nm | ||
Reaction direction | Increase | ||
Units | mg/L (nmol/L, mg/dL) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 82 µL | 72 µL | |
R2 | 28 µL | 20 µL | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2 µL | – | – |
Decreased | 4 µL | 15 µL | 75 µL |
Increased | – | – |
cobas c 501 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 12‑28 | ||
Wavelength (sub/main) | –/546 nm | ||
Reaction direction | Increase | ||
Units | mg/L (nmol/L, mg/dL) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 82 µL | 72 µL | |
R2 | 28 µL | 20 µL | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2 µL | – | – |
Decreased | 4 µL | 15 µL | 75 µL |
Increased | – | – |
CRPLX | |
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label. |
On‑board in use and refrigerated on the analyzer: | 12 weeks |
NaCl Diluent 9 % | |
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label. |
On‑board in use and refrigerated on the analyzer: | 12 weeks |
Calibrators | S1: H2O S2‑S6: C.f.a.s. Proteins | |
Multiply the lot‑specific C.f.a.s. Proteins calibrator values by the factors below to determine the standard concentrations for the 6‑point calibration curve: | ||
S2: 0.0500 | S5: 1.90 | |
S3: 0.303 | S6: 2.50 | |
S4: 0.907 | ||
Calibration mode | Line‑graph | |
Calibration frequency | Full calibration |
Traceability: This method has been standardized against the reference preparation of the IRMM (Institute for Reference Materials and Measurements) BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in Human Serum).
Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.
Precision was determined using human samples and controls in an internal protocol with repeatability (n = 21) and intermediate precision (3 aliquots per run, 1 run per day, 21 days). The following results were obtained:
Repeatability | Mean mg/L (nmol/L) | SD mg/L (nmol/L) | CV % |
Precinorm Protein | 22.4 (213, 2.24) | 0.3 (3, 0.03) | 1.2 |
Precipath Protein | 49.4 (470, 4.94) | 0.7 (7, 0.07) | 1.3 |
Human serum 1 | 5.08 (48.4, 0.51) | 0.08 (0.8, 0.01) | 1.5 |
Human serum 2 | 40.3 (384, 4.03) | 0.4 (4, 0.04) | 0.9 |
Intermediate precision | Mean mg/L (nmol/L) | SD mg/L (nmol/L) | CV % |
Precinorm Protein | 22.5 (214, 2.25) | 0.4 (4, 0.04) | 1.6 |
Precipath Protein | 51.2 (487, 5.12) | 0.7 (7, 0.07) | 1.4 |
Human serum 3 | 5.67 (54.0, 0.57) | 0.14 (1.3, 0.01) | 2.5 |
Human serum 4 | 39.9 (380, 3.99) | 0.5 (5, 0.05) | 1.3 |
CRP values for human serum and plasma samples obtained on a Roche/Hitachi cobas c 501 analyzer (y) were compared to those determined with the corresponding reagent on a Roche/Hitachi 917 analyzer (x).
Sample size (n) = 324
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.967x + 0.289 mg/L | y = 0.973x - 0.242 mg/L |
τ = 0.963 | r = 0.997 |
The sample concentrations were between 1.00 and 217 mg/L (9.52 and 2066 nmol/L). |
CRP values for human serum and plasma samples obtained on a Roche/Hitachi cobas c 501 analyzer (y) were compared to those determined with the corresponding reagent on a COBAS INTEGRA 800 analyzer (x).
Sample size (n) = 306
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 1.022x + 0.246 mg/L | y = 1.007x + 0.400 mg/L |
τ = 0.974 | r = 0.999 |
The sample concentrations were between 1.02 and 178 mg/L (9.71 and 1695 nmol/L, 0.102 and 17.8 mg/dL). |
Most tissue‑damaging processes such as infections, inflammatory diseases and malignant neoplasms are associated with a major acute phase response of the C‑reactive protein (CRP) and other acute phase reactants (e.g. AAT, AAGP, C3C, C4, HAPT). The CRP response frequently precedes clinical symptoms, including fever. In normal healthy individuals CRP is a trace protein with a range up to 5 mg/L. After onset of an acute phase response the serum CRP concentration rises rapidly and extensively. Alterations are detectable within 6 to 8 hours and the peak value is reached within 24 to 48 hours. Levels of up to thousandfold the normal value are associated with severe stimuli such as myocardial infarction, major trauma, surgery, or malignant neoplasms.
CRP activates the classical complement pathway. CRP has a half‑life of only a few hours, making it an ideal tool for clinical monitoring. Postoperative monitoring of CRP levels of patients indicates either the normal recovery process (decreasing levels to normal) or unexpected complications (persisting high levels). Measuring changes in the concentration of CRP provides useful diagnostic information about how acute and how serious a disease is. It also allows the assessment of complications during the disease and judgements about the disease genesis. Persistence of a high serum CRP concentration is usually a grave prognostic sign which generally indicates the presence of an uncontrolled infection. CRP determination may replace the classical determination of Erythrocytes Sedimentation Rate (ESR), due to its prompt response to changes in disease activity and its good correlation to ESR.
R1 | TRIS buffer with bovine serum albumin and immunoglobulins (mouse); preservative |
R2 | Latex particles coated with anti‑CRP (mouse) in glycine buffer; preservative |
R1 is in position B, and R2 is in position C.
For in vitro diagnostic use.
Exercise the normal precautions required for handling all laboratory reagents.
Disposal of all waste material should be in accordance with local guidelines.
Safety data sheet available for professional user on request.
For quality control, use control materials as listed in the \"Order information\" section.
In addition, other suitable control material can be used.
The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.
Follow the applicable government regulations and local guidelines for quality control.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum.
Plasma: Li‑heparin and K2‑EDTA plasma
The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.
Centrifuge samples containing precipitates before performing the assay.
Stability: LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002. | 11 days at 15‑25 °C 2 months at 2‑8 °C 3 years at (-15)‑(-25) °C |
C-Reactive Protein (Latex)
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