07027079500V6.

Elecsys CEA
07027079190* cobas e 402
07027079500 300
07027079214* cobas e 801
* Some kits shown may not be available in all countries.

English ▪ 1st incubation: 6 µL of sample, a biotinylated monoclonal CEA‑specific

antibody, and a monoclonal CEA‑specific antibody labeled with a
System information ruthenium complexa) react to form a sandwich complex.
Short name ACN (application code number) ▪ 2nd incubation: After addition of streptavidin-coated microparticles, the
CEA 10003 complex becomes bound to the solid phase via interaction of biotin and
streptavidin.
Please note ▪ The reaction mixture is aspirated into the measuring cell where the
microparticles are magnetically captured onto the surface of the
The measured CEA value of a patient’s sample can vary depending on electrode. Unbound substances are then removed with ProCell II M.
the testing procedure used. The laboratory finding must therefore always Application of a voltage to the electrode then induces chemiluminescent
contain a statement on the CEA assay method used. CEA values emission which is measured by a photomultiplier.
determined on patient samples by different testing procedures cannot be ▪ Results are determined via a calibration curve which is instrument-
directly compared with one another and could be the cause of erroneous specifically generated by 2‑point calibration and a master curve provided
medical interpretations. via the cobas link.
a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy) )
If there is a change in the CEA assay procedure used while monitoring
therapy, then the CEA values obtained upon changing over to the new Reagents - working solutions
procedure must be confirmed by parallel measurements with both The cobas e pack is labeled as CEA.
methods. M Streptavidin-coated microparticles, 1 bottle, 16.0 mL:
Intended use Streptavidin-coated microparticles 0.72 mg/mL; preservative.
Immunoassay for the in vitro quantitative determination of carcinoembryonic R1 Anti-CEA-Ab~biotin, 1 bottle, 21.0 mL:
antigen in human serum and plasma. This assay is further indicated for Biotinylated monoclonal anti‑CEA antibody (mouse/human) 3.0 mg/L;
serial measurement of CEA to aid in the management of cancer patients. phosphate buffer 100 mmol/L, pH 6.0; preservative.
The electrochemiluminescence immunoassay “ECLIA” is intended for use
on cobas e immunoassay analyzers. R2 Anti-CEA-Ab~Ru(bpy) , 1 bottle, 15.8 mL:
Monoclonal anti‑CEA antibody (mouse) labeled with ruthenium
Summary
complex 4.0 mg/L; phosphate buffer 100 mmol/L, pH 6.5;
Carcinoembryonic antigen (CEA) is a highly glycosylated molecule with a
molecular weight of approximately 180 kDa.1 CEA, like AFP, belongs to the preservative.
group of carcinofetal antigens that are produced during the embryonic and Precautions and warnings
fetal period. CEA has been postulated to play a role in a number of
biological processes including cell adhesion, immunity and apoptosis.2 The For in vitro diagnostic use for health care professionals. Exercise the
formation of CEA is suppressed after birth, and shows a low expression in normal precautions required for handling all laboratory reagents.
normal adult tissues.2 Therefore only very low CEA levels in the blood of Infectious or microbial waste:
healthy adults can be observed.2 The CEA gene family consists of about 17 Warning: handle waste as potentially biohazardous material. Dispose of
active genes in two subgroups. The first group contains CEA and the non- waste according to accepted laboratory instructions and procedures.
specific cross-reacting antigens (NCA); the second group contains the Environmental hazards:
pregnancy‑specific glycoproteins (PSG).3 High CEA concentrations are Apply all relevant local disposal regulations to determine the safe disposal.
frequently found in cases of colorectal adenocarcinoma.4 Slight to moderate
CEA elevations can also occur in non‑malignant diseases of the intestine, Safety data sheet available for professional user on request.
the pancreas, the liver, and the lungs (i.e. liver cirrhosis, chronic hepatitis, This kit contains components classified as follows in accordance with the
pancreatitis, ulcerative colitis, Crohn's Disease).5 Smoking can also lead to Regulation (EC) No. 1272/2008:
elevated CEA values and needs to be taken into account when interpreting
CEA levels.6 CEA determinations are not recommended for
cancer‑screening in the general population and CEA concentrations within
the normal range do not exclude the possible presence of a malignant
disease. The main indication for CEA determinations is to monitor colorectal
carcinoma treatment, to identify recurrences after treatment or surgical
resection and to aid in staging and assessing metastasis.7 Warning
Preoperative measurement of CEA is desirable as this may give H317 May cause an allergic skin reaction.
independent prognostic information, help with surgical management and
provide a baseline level for subsequent determinations. For patients with H412 Harmful to aquatic life with long lasting effects.
stage II and III, CEA levels should be measured every 2‑3 months for at
least 3 years after diagnosis. For monitoring treatment of advanced Prevention:
disease, CEA should also be tested every 2‑3 months.8,9 The antibodies
inside the Elecsys CEA assay react with CEA and with the meconium P261 Avoid breathing dust/fume/gas/mist/vapours/spray.
antigen NCA‑210,11 and especially the cross-reaction with NCA‑2 was found
to be useful in early detection of colorectal cancer metastasis and relapse.12 P273 Avoid release to the environment.
The antigenic determinants of CEA have been characterized, and the
available monoclonal antibodies were classified into 5 epitope groups.2,11 P280 Wear protective gloves.
The antibodies used in the Elecsys CEA assay react with epitopes 2 and 5. Response:
Test principle
P333 + P313 If skin irritation or rash occurs: Get medical
Sandwich principle. Total duration of assay: 18 minutes.
advice/attention.

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Elecsys CEA
P362 + P364 Take off contaminated clothing and wash it before reuse. ▪ 05694302001, Assay Tip/Assay Cup tray, 6 magazines
x 6 magazine stacks x 105 assay tips and 105 assay cups, 3 wasteliners
Disposal:
▪ 07485425001, Liquid Flow Cleaning Cup, 2 adaptor cups to supply
P501 Dispose of contents/container to an approved waste ISE Cleaning Solution/Elecsys SysClean for Liquid Flow Cleaning
disposal plant. Detection Unit
Product safety labeling follows EU GHS guidance. ▪ 07485433001, PreWash Liquid Flow Cleaning Cup, 1 adaptor cup
to supply ISE Cleaning Solution/Elecsys SysClean for Liquid Flow
Contact phone: all countries: +49-621-7590 Cleaning PreWash Unit
Avoid foam formation in all reagents and sample types (specimens, ▪ 11298500316, ISE Cleaning Solution/Elecsys SysClean,
calibrators and controls). 5 x 100 mL system cleaning solution
Reagent handling Assay
The reagents in the kit have been assembled into a ready‑for‑use unit that For optimum performance of the assay follow the directions given in this
cannot be separated. document for the analyzer concerned. Refer to the appropriate operator’s
All information required for correct operation is available via the cobas link. manual for analyzer‑specific assay instructions.
Storage and stability Resuspension of the microparticles takes place automatically prior to use.
Store at 2‑8 °C. Place the cooled (stored at 2‑8 °C) cobas e pack on the reagent manager.
Do not freeze. Avoid foam formation. The system automatically regulates the temperature
of the reagents and the opening/closing of the cobas e pack.
Store the cobas e pack upright in order to ensure complete availability of
the microparticles during automatic mixing prior to use. Calibration
Traceability: This method has been standardized against the 1st IRP WHO
Stability: Reference Standard 73/601.
unopened at 2‑8 °C up to the stated expiration date The predefined master curve is adapted to the analyzer using the relevant
CalSet.
on the analyzers 16 weeks
Calibration frequency: Calibration must be performed once per reagent lot
Specimen collection and preparation using fresh reagent (i.e. not more than 24 hours since the cobas e pack
Only the specimens listed below were tested and found acceptable. was registered on the analyzer).
Serum collected using standard sampling tubes or tubes containing Calibration interval may be extended based on acceptable verification of
separating gel. calibration by the laboratory.
Li‑heparin, K2‑EDTA and K3‑EDTA plasma. Renewed calibration is recommended as follows:
Plasma tubes containing separating gel can be used. ▪ after 12 weeks when using the same reagent lot
Criterion: Slope 0.9‑1.1 + coefficient of correlation ≥ 0.95. ▪ after 28 days when using the same cobas e pack on the analyzer
Stable for 7 days at 20‑25 °C, 14 days at 2‑8 °C, 6 months at ▪ as required: e.g. quality control findings outside the defined limits
‑20 °C (± 5 °C). The samples may be frozen 3 times. Quality control
The sample types listed were tested with a selection of sample collection For quality control, use PreciControl Tumor Marker or PreciControl
tubes that were commercially available at the time of testing, i.e. not all Universal.
available tubes of all manufacturers were tested. Sample collection systems
from various manufacturers may contain differing materials which could In addition, other suitable control material can be used.
affect the test results in some cases. When processing samples in primary Controls for the various concentration ranges should be run individually at
tubes (sample collection systems), follow the instructions of the tube least once every 24 hours when the test is in use, once per cobas e pack,
manufacturer. and following each calibration.
Centrifuge samples containing precipitates before performing the assay. The control intervals and limits should be adapted to each laboratory’s
Do not use heat‑inactivated samples. individual requirements. Values obtained should fall within the defined
limits. Each laboratory should establish corrective measures to be taken if
Do not use samples and controls stabilized with azide. values fall outside the defined limits.
Ensure the samples and calibrators are at 20‑25 °C prior to measurement. If necessary, repeat the measurement of the samples concerned.
Due to possible evaporation effects, samples and calibrators on the Follow the applicable government regulations and local guidelines for
analyzers should be analyzed/measured within 2 hours. quality control.
Materials provided Calculation
See “Reagents – working solutions” section for reagents. The analyzer automatically calculates the analyte concentration of each
Materials required (but not provided) sample (either in ng/mL or µg/L).
▪ 11731645322, CEA CalSet, 4 x 1.0 mL 1 ng/mL CEA corresponds to 16.9 mIU/mL.
▪ 11776452122, PreciControl Tumor Marker, for 4 x 3.0 mL or Limitations - interference
11731416190, PreciControl Universal, for 4 x 3.0 mL The effect of the following endogenous substances and pharmaceutical
▪ 07299001190, Diluent Universal, 36 mL sample diluent compounds on assay performance was tested. Interferences were tested
up to the listed concentrations and no impact on results was observed.
▪ General laboratory equipment
Endogenous substances
▪ cobas e analyzer
Additional materials for cobas e 402 and cobas e 801 analyzers: Compound Concentration tested
▪ 06908799190, ProCell II M, 2 x 2 L system solution Bilirubin ≤ 1130 µmol/L or ≤ 66 mg/dL
▪ 04880293190, CleanCell M, 2 x 2 L measuring cell cleaning Hemoglobin ≤ 0.621 mmol/L or ≤ 1000 mg/dL
solution
Intralipid ≤ 2000 mg/dL
▪ 07485409001, Reservoir Cup, 8 cups to supply ProCell II M and
CleanCell M Biotin ≤ 286 nmol/L or ≤ 70 ng/mL
▪ 06908853190, PreClean II M, 2 x 2 L wash solution Rheumatoid factors ≤ 1200 IU/mL

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Elecsys CEA
Criterion: Recovery ± 1 ng/mL of initial value ≤ 10 ng/mL and ± 10 % of For Limit of Quantitation ≥ 4 human serum samples were measured over
initial value > 10 ng/mL. 5 days with 5 replicates per day on one analyzer. With an intermediate
Samples should not be taken from patients receiving therapy with high precision CV of ≤ 20 % the Limit of Quantitation was 0.403 ng/mL.
biotin doses (i.e. > 5 mg/day) until at least 8 hours following the last biotin Dilution
administration. Samples with CEA concentrations above the measuring range can be
There is no high-dose hook effect at CEA concentrations up to diluted with Diluent Universal. The recommended dilution is 1:50 (either
200000 ng/mL. automatically by the analyzer or manually). The concentration of the diluted
Pharmaceutical substances sample must be ≥ 20 ng/mL).
In vitro tests were performed on 16 commonly used pharmaceuticals. No After manual dilution, multiply the result by the dilution factor.
interference with the assay was found. After dilution by the analyzer, the software automatically takes the dilution
In addition, the following special cancer drugs were tested. No interference into account when calculating the sample concentration.
with the assay was found.
Expected values
Special cancer drugs Studies with the Elecsys CEA assay were performed on 352 healthy
subjects. The following results were obtained:
Drug Concentration tested
mg/L All subjects Non-smokers Smokers
Carboplatin 1000 (past/never (current)
smokers)
Cisplatin 225
Age (years) 20-69 40-69 20-69 40-69 20-69 40-69
Cyclophosphamide 1000
95thpercentile 4.7 5.2 3.8 5.0 5.5 6.5
Doxorubicin 75
(ng/mL)
Etoposide 400
N 352 203 242 154 110 49
Fluorouracil 500
Each laboratory should investigate the transferability of the expected values
Flutamide 1000 to its own patient population and if necessary determine its own reference
Methotrexate 1000 ranges.
Mitomycin 25 Specific performance data
Representative performance data on the analyzers are given below.
Tamoxifen 50 Results obtained in individual laboratories may differ.
Taxol 5.5 Precision
In rare cases, interference due to extremely high titers of antibodies to Precision was determined using Elecsys reagents, samples and controls in
analyte‑specific antibodies, streptavidin or ruthenium can occur. These a protocol (EP05‑A3) of the CLSI (Clinical and Laboratory Standards
effects are minimized by suitable test design. Institute): 2 runs per day in duplicate each for 21 days (n = 84). The
For diagnostic purposes, the results should always be assessed in following results were obtained:
conjunction with the patient’s medical history, clinical examination and other
findings. cobas e 402 and cobas e 801 analyzers

Limits and ranges Repeatability Intermediate

Measuring range precision
0.3‑1000 ng/mL (defined by the Limit of Blank and the maximum of the Sample Mean SD CV SD CV
master curve). Values below the Limit of Blank are reported as < 0.3 ng/mL. ng/mL ng/mL % ng/mL %
Values above the measuring range are reported as > 1000 ng/mL (or up to Human serum 1 0.863 0.0209 2.4 0.0227 2.6
50000 ng/mL for 50‑fold diluted samples).
Lower limits of measurement Human serum 2 1.77 0.0486 2.8 0.0581 3.3
Limit of Blank, Limit of Detection and Limit of Quantitation Human serum 3 3.77 0.0659 1.7 0.0823 2.2
Limit of Blank = 0.3 ng/mL Human serum 4 522 10.8 2.1 12.1 2.3
Limit of Detection = 0.6 ng/mL Human serum 5 930 20.5 2.2 21.3 2.3
Limit of Quantitation = 1.8 ng/mL
PreciControl TMb)1 4.96 0.0797 1.6 0.103 2.1
The Limit of Blank, Limit of Detection and Limit of Quantitation were
determined in accordance with the CLSI (Clinical and Laboratory Standards PreciControl TM2 47.6 0.710 1.5 0.979 2.1
Institute) EP17‑A2 requirements. PreciControl Uc)1 4.63 0.0758 1.6 0.104 2.2
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of
analyte‑free samples over several independent series. The Limit of Blank PreciControl U2 47.6 0.744 1.6 0.851 1.8
corresponds to the concentration below which analyte‑free samples are b) TM = Tumor Marker
found with a probability of 95 %. c) U = Universal
The Limit of Detection is determined based on the Limit of Blank and the Method comparison
standard deviation of low concentration samples. The Limit of Detection
corresponds to the lowest analyte concentration which can be detected A comparison of the Elecsys CEA assay, 07027079190 (cobas e 801
(value above the Limit of Blank with a probability of 95 %). analyzer; y) with the Elecsys CEA assay, 11731629322 (cobas e 601
analyzer; x) gave the following correlations (ng/mL):
The Limit of Quantitation is the lowest analyte concentration that can be
reproducibly measured with an intermediate precision CV of ≤ 20 %. Number of serum samples measured: 141
An internal study was performed based on guidance from the CLSI protocol Passing/Bablok13 Linear regression
EP17‑A2 . Limit of Blank and Limit of Detection were determined to be the
following: y = 1.02x + 0.021 y = 1.01x + 1.09
Limit of Blank = 0.134 ng/mL τ = 0.993 r = 1.00
Limit of Detection = 0.269 ng/mL The sample concentrations were between 0.641 and 965 ng/mL.

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Elecsys CEA
A comparison of the Elecsys CEA assay, 07027079190 (cobas e 402 Symbols
analyzer; y) with the Elecsys CEA assay, 07027079190 (cobas e 801 Roche Diagnostics uses the following symbols and signs in addition to
analyzer; x) gave the following correlations ng/mL): those listed in the ISO 15223‑1 standard (for USA: see dialog.roche.com for
Number of samples measured: 139 definition of symbols used):
Passing/Bablok13 Linear regression Contents of kit
y = 0.979x + 0.183 y = 0.975x + 0.818 Analyzers/Instruments on which reagents can be used
τ = 0.984 r = 1.00 Reagent
The sample concentrations were between 0.488 and 986 ng/mL. Calibrator
Analytical specificity Volume for reconstitution
No investigations into possible cross‑reactivity with glycoproteins from the
lungs and liver have been performed. GTIN Global Trade Item Number
References COBAS, COBAS E, ELECSYS and PRECICONTROL are trademarks of Roche. INTRALIPID is a trademark of
1 Thompson J, Zimmermann W. The carcinoembryonic antigen gene Fresenius Kabi AB.
family: structure, expression and evolution. Tumour Biol All other product names and trademarks are the property of their respective owners.
1988;9(2-3):63-83. Additions, deletions or changes are indicated by a change bar in the margin.
2 Hammarström S. The carcinoembryonic antigen (CEA) family: © 2022, Roche Diagnostics
structures, suggested functions and expression in normal and
malignant tissues. Semin Cancer Biol 1999;9(2):67-81.
3 Thompson JA. Molecular cloning and expression of carcinoembryonic
antigen gene family members. Tumor Biol 1995;16:10-16. Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305 Mannheim
www.roche.com
4 Ballesta AM, Molina R, Filella X, et al. Carcinoembryonic Antigen in +800 5505 6606
Staging and Follow-up of Patients with Solid Tumors. Tumor Biol
1995;16:32-41.
5 Ruibal Morell A. CEA serum levels in nonneoplastic disease. Int J Biol
Markers 1992;7(3):160-166.
6 Fukuda I, Yamakado M, Kiyose H. Influence of Smoking on Serum
Carcinoembryonic Antigen Levels in Subjects Who Underwent
Multiphasic Health Testing and Services. J Med Syst 1998;22(2):89-93.
7 Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer.
Is it clinically useful? Clin Chem 2001; 47(4): 624-630.
8 Duffy MJ, Van Dalen A, Haglund C, et al. Clinical utility of biochemical
markers in colorectal cancer: European Group on Tumour Markers
(EGTM) guidelines. Eur J Cancer 2003;39(6): 718-727.
9 Sturgeon CM, Duffy MJ, Stenman UH, et al. National Academy of
Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use
of Tumor Markers in Testicular, Prostate, Colorectal, Breast and
Ovarian Cancers. Clin Chem 2008;54(12): e11-e79.
10 Kuroki M, Haruno M, Arakawa F, et al. Reaction profiles of seven
enzyme immunoassay kits for carcinoembryonic antigen (CEA)
analyzed with purified preparations of CEA and related normal
antigens. Clin Biochem 1992;25:29-35.
11 Bormer OP, Thrane-Steen K. Epitope group specificity of six
immunoassays for carcino-embryonic antigen. Tumor Biol
1991;12:9-15.
12 Hanada H, Muggi S, Takeoka K, et al. Early detection of colorectal
cancer metastasis and relapse by recognizing non-specific cross-
reacting antigen 2 in commercial carcinoembryonic antigen assays.
Clin Chem 2009;55(9):1747-1748.
13 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.
For further information, please refer to the appropriate operator’s manual for
the analyzer concerned, the respective application sheets and the Method
Sheets of all necessary components (if available in your country).
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.
The Summary of Safety & Performance Report can be found here:
https://ec.europa.eu/tools/eudamed

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