0108057591190c503V5.

CRP4
Tina-quant C-Reactive Protein IV
Order information
Analyzer(s) on which cobas c pack(s) can be
used
08057591190 Tina-quant C‑Reactive Protein IV (500 tests) System‑ID 2050 001 cobas c 303, cobas c 503
Materials required (but not provided):
11355279216 Calibrator f.a.s. Proteins (5 × 1 mL) Code 20656
20766321322 CRP T Control N (5 × 0.5 mL) Code 20235
10557897122 Precinorm Protein (3 × 1 mL) Code 20302
11333127122 Precipath Protein (3 × 1 mL) Code 20303
05117003190 PreciControl ClinChem Multi 1 (20 × 5 mL) Code 20391
05947626190 PreciControl ClinChem Multi 1 (4 × 5 mL) Code 20391
05117216190 PreciControl ClinChem Multi 2 (20 × 5 mL) Code 20392
05947774190 PreciControl ClinChem Multi 2 (4 × 5 mL) Code 20392
08063494190 Diluent NaCl 9 % (123 mL) System‑ID 2906 001

English Precautions and warnings

System information For in vitro diagnostic use for health care professionals. Exercise the
normal precautions required for handling all laboratory reagents.
CRP4: ACN 20500
Infectious or microbial waste:
Intended use Warning: handle waste as potentially biohazardous material. Dispose of
Immunoturbidimetric assay for the in vitro quantitative determination of CRP waste according to accepted laboratory instructions and procedures.
in human serum and plasma on cobas c systems. Environmental hazards:
Summary1,2,3,4,5,6,7,8 Apply all relevant local disposal regulations to determine the safe disposal.
C‑reactive protein is the classic acute phase protein in inflammatory Safety data sheet available for professional user on request.
reactions. It is synthesized by the liver and consists of five identical This kit contains components classified as follows in accordance with the
polypeptide chains that form a five‑membered ring having a molecular Regulation (EC) No. 1272/2008:
weight of 105000 daltons. CRP is the most sensitive of the acute phase
reactants and its concentration increases rapidly during inflammatory
processes. Complexed CRP activates the classical complement pathway.
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. The increase begins within 6 to Warning
12 hours and the peak value is reached within 24 to 48 hours. Levels above
100 mg/L are associated with severe stimuli such as major trauma and H317 May cause an allergic skin reaction.
severe infection (sepsis). CRP response may be less pronounced in
patients suffering from liver disease. CRP assays are used to detect H412 Harmful to aquatic life with long lasting effects.
systemic inflammatory processes; to assess treatment of bacterial
infections with antibiotics; to detect intrauterine infections with concomitant Prevention:
premature amniorrhexis; to differentiate between active and inactive forms
of disease with concurrent infection, e.g. in patients suffering from SLE or P261 Avoid breathing dust/fume/gas/mist/vapours/spray.
Colitis ulcerosa; to therapeutically monitor rheumatic disease and assess
anti‑inflammatory therapy; to determine the presence of post‑operative P273 Avoid release to the environment.
complications at an early stage, such as infected wounds, thrombosis and
pneumonia, and to distinguish between infection and bone marrow P280 Wear protective gloves.
rejection. Postoperative monitoring of CRP levels of patients can aid in the Response:
recognition of unexpected complications (persisting high or increasing
levels). Measuring changes in the concentration of CRP provides useful P333 + P313 If skin irritation or rash occurs: Get medical
diagnostic information about how acute and how serious a disease is. It advice/attention.
also allows judgements about the disease genesis. Persistence of a high
serum CRP concentration is usually a grave prognostic sign which P362 + P364 Take off contaminated clothing and wash it before reuse.
generally indicates the presence of an uncontrolled infection.
Test principle9,10 Disposal:
Particle‑enhanced immunoturbidimetric assay P501 Dispose of contents/container to an approved waste
Human CRP agglutinates with latex particles coated with monoclonal disposal plant.
anti‑CRP antibodies. The aggregates are determined turbidimetrically.
Product safety labeling follows EU GHS guidance.
Reagents - working solutions
Contact phone: all countries: +49-621-7590
R1 TRISa) buffer with bovine serum albumin; preservatives Reagent handling
R3 Latex particles coated with anti‑CRP (mouse) in glycine buffer; Ready for use
immunoglobulins (mouse); preservative Carefully invert reagent container several times prior to use to ensure that
a) TRIS = Tris(hydroxymethyl)-aminomethane
the reagent components are mixed.
R1 is in position B and R3 is in position C. Storage and stability
Shelf life at 2‑8 °C: See expiration date on
cobas c pack label.

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CRP4
Tina-quant C-Reactive Protein IV

On‑board in use and refrigerated on the 12 weeks Calibration

analyzer:
Calibrators S1: H2O
Specimen collection and preparation S2: Calibrator f.a.s. Proteins
For specimen collection and preparation only use suitable tubes or
collection containers. Calibration mode Non-linear
Only the specimens listed below were tested and found acceptable. Calibration frequency Full calibration
Serum - after reagent lot change
Plasma: Li‑heparin, K2‑EDTA, K3‑EDTA plasma - after 3 weeks on-board the analyzer
The sample types listed were tested with a selection of sample collection - after 6 months when using a single reagent
tubes that were commercially available at the time of testing, i.e. not all lot
available tubes of all manufacturers were tested. Sample collection systems
from various manufacturers may contain differing materials which could - as required following quality control
affect the test results in some cases. When processing samples in primary procedures
tubes (sample collection systems), follow the instructions of the tube Calibration interval may be extended based on acceptable verification of
manufacturer. calibration by the laboratory.
Centrifuge samples containing precipitates before performing the assay. This method has been standardized against the certified reference material
See the limitations and interferences section for details about possible in human serum of the IRMM (Institute for Reference Materials and
sample interferences. Measurements) ERM‑DA474/IFCC.11
Stability in serum and 2 weeks at 15‑25 °C Quality control
Li‑heparin plasma: For quality control, use control materials as listed in the “Order information”
3 weeks at 2‑8 °C section. In addition, other suitable control material can be used.
12 months at −20 (± 5 °C) The control intervals and limits should be adapted to each laboratory’s
Stability in K2‑ and K3‑EDTA plasma: 1 day at 15‑25 °C individual requirements. It is recommended to perform quality control
always after lot calibration and subsequently at least every 12 weeks.
3 weeks at 2‑8 °C Values obtained should fall within the defined limits. Each laboratory should
establish corrective measures to be taken if values fall outside the defined
12 months at −20 (± 5 °C) limits.
Sample stability claims were established by experimental data by the Follow the applicable government regulations and local guidelines for
manufacturer or based on reference literature and only for the quality control.
temperatures/time frames as stated in the method sheet. It is the
responsibility of the individual laboratory to use all available references Calculation
and/or its own studies to determine specific stability criteria for its cobas c systems automatically calculate the analyte concentration of each
laboratory. sample in the unit mg/L (nmol/L, mg/dL).
Materials provided Conversion factors: mg/L × 9.52 = nmol/L
See “Reagents – working solutions” section for reagents.
mg/L × 0.1 = mg/dL
Materials required (but not provided)
See “Order information” section Limitations - interference
Criterion: Recovery within ± 0.5 mg/L of initial values of samples ≤ 5.0 mg/L
General laboratory equipment and within ± 10 % for samples > 5 mg/L.
Assay Icterus:12 No significant interference up to an I index of 60 for conjugated
For optimum performance of the assay follow the directions given in this and unconjugated bilirubin (approximate conjugated and unconjugated
document for the analyzer concerned. Refer to the appropriate operator’s bilirubin concentration: 60 mg/dL or 1026 µmol/L).
manual for analyzer‑specific assay instructions. Hemolysis:12 No significant interference up to an H index of 1000
The performance of applications not validated by Roche is not warranted (approximate hemoglobin concentration: 622 µmol/L or 1000 mg/dL).
and must be defined by the user. Lipemia (Intralipid):12 No significant interference up to an L index of 1000.
Application for serum and plasma There is poor correlation between the L index (corresponds to turbidity) and
triglycerides concentration.
Test definition Rheumatoid factors: No significant interference from rheumatoid factors up
Reporting time 10 min to a concentration of 1200 IU/mL.
Wavelength (sub/main) 800/570 nm Immunoglobulins: No significant interference from immunoglobulins up to a
concentration of 50 g/L (334 µmol/L) (simulated by human
Reagent pipetting Diluent (H2O) immunoglobulin G).
R1 98 µL High-dose hook effect: No false result occurs up to a CRP concentration of
1200 mg/L.
R3 31 µL 16 µL
In vitro tests were performed on commonly used pharmaceuticals. In
addition, special pharmaceuticals were tested. Among them, the following
substance caused interference:
Sample volumes Sample Sample dilution
Sample Diluent (NaCl) Substance No significant interference up to
Normal 1.3 µL – – Ticarcillin 225 mg/L
Decreased 2.6 µL 20 µL 60 µL Drug interferences are measured based on recommendations given in CLSI
guidelines EP07 and EP37 and other published literature. Effects of
Increased 1.3 µL – – concentrations exceeding these recommendations have not been
For further information about the assay test definitions refer to the characterized.
application parameters setting screen of the corresponding analyzer and As with any assay employing mouse antibodies, the possibility exists for
assay. interference by human anti‑mouse antibodies (HAMA) in the sample, which
could cause falsely lowered results.

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Tina-quant C-Reactive Protein IV

In very rare cases, gammopathy, in particular type IgM (Waldenström’s Human serum 2 4.09 0.0338 0.8
macroglobulinemia), may cause unreliable results.13
Human serum 3 82.9 0.474 0.6
For diagnostic purposes, the results should always be assessed in
conjunction with the patient’s medical history, clinical examination and other Human serum 4 174 1.37 0.8
findings. Human serum 5 305 2.10 0.7
ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory Intermediate precision Mean SD CV
when certain test combinations are run together on cobas c systems. All mg/L mg/L %
special wash programming necessary for avoiding carry-over is available
via the cobas link. The latest version of the carry-over evasion list can be CRP T Control N 3.33 0.0375 1.1
found with the NaOHD/SMS/SCCS Method Sheet for information. For Precinorm Protein 9.72 0.0708 0.7
further instructions refer to the operator’s manual.
Precipath Protein 53.9 0.854 1.6
Limits and ranges
Measuring range Human serum 1 1.11 0.0296 2.7
0.6‑350 mg/L (5.7‑3332 nmol/L) Human serum 2 4.09 0.0397 1.0
Determine samples having higher concentrations via the rerun function. Human serum 3 82.9 1.61 1.9
Dilution of samples via the rerun function is a 1:2 dilution. Results from
samples diluted using the rerun function are automatically multiplied by a Human serum 4 174 3.94 2.3
factor of 2. Human serum 5 305 5.79 1.9
Lower limits of measurement
The data obtained on cobas c 503 analyzer(s) are representative for
Limit of Blank, Limit of Detection and Limit of Quantitation cobas c 303 analyzer(s).
Limit of Blank = 0.2 mg/L (1.9 nmol/L) Method comparison
Limit of Detection = 0.3 mg/L (2.9 nmol/L) CRP values for human serum and plasma samples obtained on a
cobas c 503 analyzer (y) were compared with those determined using the
Limit of Quantitation = 0.6 mg/L (5.7 nmol/L) corresponding reagent on a cobas c 501 analyzer (x).
The Limit of Blank, Limit of Detection and Limit of Quantitation were Sample size (n) = 157
determined in accordance with the CLSI (Clinical and Laboratory Standards
Institute) EP17‑A2 requirements. Passing/Bablok15 Linear regression
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of y = 0.990x + 0.124 mg/L y = 0.978x + 0.428 mg/L
analyte‑free samples over several independent series. The Limit of Blank
corresponds to the concentration below which analyte‑free samples are τ = 0.995 r = 1.000
found with a probability of 95 %. The sample concentrations were between 0.791 and 333 mg/L.
The Limit of Detection is determined based on the Limit of Blank and the CRP values for human serum and plasma samples obtained on a
standard deviation of low concentration samples. cobas c 303 analyzer (y) were compared with those determined using the
The Limit of Detection corresponds to the lowest analyte concentration corresponding reagent on a cobas c 501 analyzer (x).
which can be detected (value above the Limit of Blank with a probability of
95 %). Sample size (n) = 79
The Limit of Quantitation is the lowest analyte concentration that can be Passing/Bablok15 Linear regression
reproducibly measured with a total error of 20 %. It has been determined
using low concentration C‑reactive protein samples. y = 0.976x - 0.0226 mg/L y = 0.973x + 0.340 mg/L
Expected values τ = 0.989 r = 1.000
Consensus reference interval for adults:14 < 5 mg/L (< 47.6 nmol/L*) The sample concentrations were between 0.920 and 348 mg/L.
*calculated by unit conversion factor
References
Each laboratory should investigate the transferability of the expected values 1 Greiling H, Gressner AM, eds. Lehrbuch der Klinischen Chemie und
to its own patient population and if necessary determine its own reference Pathobiochemie, 3rd ed. Stuttgart/New York: Schattauer Verlag
ranges. 1995:234-236.
Specific performance data 2 Thomas L. Labor und Diagnose, 7. Auflage, TH-Books
Representative performance data on the analyzers are given below. These Verlagsgesellschaft mbH, Frankfurt/Main 2008;1010-1021.
data represent the performance of the analytical procedure itself. 3 Burtis CA, Ashwood ER, eds. Tietz Fundamentals of Clinical
Results obtained in individual laboratories may differ due to heterogenous Chemistry, 5th ed. Pa: WB Saunders Co 2001;332-333.
sample materials, aging of analyzer components and mixture of reagents 4 Thomas L, Messenger M. Pathobiochemie und Labordiagnostik der
running on the analyzer. Entzündung. Lab med 1993;17:179–194.
Precision 5 Young B, Gleeson M, Cripps AW. C-reactive protein: A critical review.
Precision was determined using human samples and controls in Pathology 1991;23:118-124.
accordance with the CLSI (Clinical and Laboratory Standards Institute)
EP5‑A3 requirements with repeatability (n = 84) and intermediate precision 6 Wasunna A, Whitelaw A, Gallimore R, et al. C-reactive protein and
(2 aliquots per run, 2 runs per day, 21 days). Results for repeatability and bacterial infection in preterm infants. Eur J Pediatr 1990
intermediate precision were obtained on the cobas c 503 analyzer. Mar;149(6):424-427.
7 Vergis N. Should CRP be used as a marker of infection in patients with
Repeatability Mean SD CV liver cirrhosis? Clin Lab Int 2007;6:12-13.
mg/L mg/L % 8 Mackenzie I, Woodhouse J. C-reactive protein concentrations during
CRP T Control N 3.33 0.0313 0.9 bacteraemia: a comparison between patients with and without liver
dysfunction. Intensive Care Medicine 2006;32:1344-1351.
Precinorm Protein 9.72 0.0516 0.5
9 Price CP, Trull AK, Berry D, et al. Development and validation of a
Precipath Protein 53.9 0.275 0.5 particle-enhanced turbidimetric immunoassay for C-reactive protein. J
Human serum 1 1.11 0.0276 2.5 Immunol Methods 1987;99:205-211.

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CRP4
Tina-quant C-Reactive Protein IV

10 Eda S, Kaufmann J, Roos W, et al. Development of a New

Microparticle-Enhanced Turbidimetric Assay for C-reactive Protein with
Superior Features in Analytical Sensitivity and Dynamic Range. J Clin
Lab Anal 1998;12:137-144.
11 Auclair G, Zegers I, Charoud-Got J, et al. CERTIFICATION REPORT.
The Certification of the Mass Concentration of C-Reactive Protein in
Human Serum. Publications Office of the European Union, 2011.
http://www.jrc.ec.europa.eu/
12 Glick MR, Ryder KW, Jackson SA. Graphical Comparisons of
Interferences in Clinical Chemistry Instrumentation. Clin Chem
1986;32:470-475.
13 Bakker AJ, Mücke M. Gammopathy interference in clinical chemistry
assays: mechanisms, detection and prevention.
Clin Chem Lab Med 2007;45(9):1240-1243.
14 Dati F, Schumann G, Thomas L, et al. Consensus of a group of
professional societies and diagnostic companies on guidelines for
interim reference ranges for 14 proteins in serum based on the
standardization against the IFCC/BCR/CAP reference material (CRM
470). Eur J Clin Chem Clin Biochem 1996;34:517-520.
15 Bablok 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.
A point (period/stop) is always used in this Method Sheet as the decimal
separator to mark the border between the integral and the fractional parts of
a decimal numeral. Separators for thousands are not used.
Any serious incident that has occurred in relation to the device shall be
reported to the manufacturer and the competent authority of the Member
State in which the user and/or the patient is established.
Symbols
Roche Diagnostics uses the following symbols and signs in addition to
those listed in the ISO 15223‑1 standard (for USA: see dialog.roche.com for
definition of symbols used):
Contents of kit
Volume for reconstitution
GTIN Global Trade Item Number

COBAS, COBAS C, PRECICONTROL, PRECINORM, PRECIPATH and TINA‑QUANT are trademarks of Roche.
All other product names and trademarks are the property of their respective owners.
Additions, deletions or changes are indicated by a change bar in the margin.
© 2022, Roche Diagnostics

Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305 Mannheim

www.roche.com
+800 5505 6606

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