11731629501V9.

Elecsys CEA
MODULAR ANALYTICS E170
cobas e 411
11731629160 11731629501 100
cobas e 601
cobas e 602

English ▪ The reaction mixture is aspirated into the measuring cell where the
microparticles are magnetically captured onto the surface of the
For use in the USA only electrode. Unbound substances are then removed with
System Information ProCell/ProCell M. Application of a voltage to the electrode then induces
chemiluminescent emission which is measured by a photomultiplier.
For cobas e 411 analyzer: test number 301
For MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 ▪ Results are determined via a calibration curve which is instrument-
analyzers: Application Code Number 049 specifically generated by 2‑point calibration and a master curve provided
via the reagent barcode or e‑barcode.
Please note a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy) )
The measured CEA value of a patient's sample can vary depending on Reagents - working solutions
the testing procedure used. The laboratory finding must therefore always The reagent rackpack is labeled as CEA.
contain a statement on the Elecsys CEA assay method used. CEA values
determined on patient samples by different testing procedures cannot be M Streptavidin‑coated microparticles (transparent cap), 1 bottle, 8 mL:
directly compared with one another and could be the cause of erroneous Streptavidin‑coated microparticles 0.72 mg/mL; preservative.
medical interpretations. If there is a change in the Elecsys CEA assay R1 Anti‑CEA‑Ab~biotin (gray cap), 1 bottle, 10 mL:
procedure used while monitoring therapy, then the CEA values obtained Biotinylated monoclonal anti‑CEA antibody (mouse/human) 3.0 mg/L;
upon changing over to the new procedure must be confirmed by parallel phosphate buffer 100 mmol/L, pH 6.0; preservative.
measurements with both methods.
R2 Anti‑CEA‑Ab~Ru(bpy) (black cap), 1 bottle, 8 mL:
Caution: US Federal law restricts this device to sale and distribution by or
Monoclonal anti‑CEA antibody (mouse) labeled with ruthenium
on the order of a physician, or to a laboratory; and its use is restricted to,
complex 4.0 mg/L; phosphate buffer 100 mmol/L, pH 6.5;
by or on the order of a physician.
preservative.
Intended use
Precautions and warnings
Immunoassay for the in vitro quantitative determination of carcinoembryonic
antigen in human serum and plasma. This assay is further indicated for For in vitro diagnostic use.
serial measurement of CEA to aid in the management of cancer patients. Exercise the normal precautions required for handling all laboratory
reagents.
The electrochemiluminescence immunoassay “ECLIA” is intended for use Disposal of all waste material should be in accordance with local guidelines.
on Elecsys and cobas e immunoassay analyzers. Safety data sheet available for professional user on request.
Summary For USA: Caution: Federal law restricts this device to sale by or on the
Carcinoembryonic antigen (CEA) is a highly glycosylated molecule with a order of a physician.
molecular weight of approximately 180 kDa.1 CEA, like AFP, belongs to the This kit contains components classified as follows in accordance with the
group of carcinofetal antigens that are produced during the embryonic and Regulation (EC) No. 1272/2008:
fetal period. CEA has been postulated to play a role in a number of
biological processes including cell adhesion, immunity and apoptosis.2 The 2-methyl-2H-isothiazol-3-one hydrochloride
formation of CEA is suppressed after birth, and shows a low expression in EUH 208 May produce an allergic reaction.
normal adult tissues.2 Therefore only very low CEA levels in the blood of
healthy adults can be observed.2 The CEA gene family consists of about 17 Product safety labeling follows EU GHS guidance.
active genes in two subgroups. The first group contains CEA and the non- All human material should be considered potentially infectious. All products
specific cross-reacting antigens (NCA); the second group contains the derived from human blood are prepared exclusively from the blood of
pregnancy‑specific glycoproteins (PSG).3 High CEA concentrations are donors tested individually and shown to be free from HBsAg and antibodies
frequently found in cases of colorectal adenocarcinoma.4 Slight to moderate to HCV and HIV. The testing methods used assays approved by the FDA or
CEA elevations can also occur in non‑malignant diseases of the intestine, cleared in compliance with the European Directive 98/79/EC, Annex II,
the pancreas, the liver, and the lungs (i.e. liver cirrhosis, chronic hepatitis, List A.
pancreatitis, ulcerative colitis, Crohn's Disease).5 Smoking can also lead to
elevated CEA values and needs to be taken into account when interpreting However, as no testing method can rule out the potential risk of infection
CEA levels.6 CEA determinations are not recommended for with absolute certainty, the material should be handled with the same level
cancer‑screening in the general population and CEA concentrations within of care as a patient specimen. In the event of exposure, the directives of the
the normal range do not exclude the possible presence of a malignant responsible health authorities should be followed.8,9
disease. The main indication for CEA determinations is the follow‑up and Avoid foam formation in all reagents and sample types (specimens,
therapy‑management of colorectal carcinoma. calibrators and controls).
The antigenic determinants of CEA have been characterized, and the Reagent handling
available monoclonal antibodies were classified into 5 epitope groups.2,7 The reagents in the kit have been assembled into a ready‑for‑use unit that
The antibodies used in the Elecsys CEA assay react with epitopes 2 and 5. cannot be separated.
Test principle All information required for correct operation is read in from the respective
Sandwich principle. Total duration of assay: 18 minutes. reagent barcodes.
▪ 1st incubation: 10 µL of sample, a biotinylated monoclonal CEA‑specific Storage and stability
antibody, and a monoclonal CEA‑specific antibody labeled with a Store at 2‑8 °C.
ruthenium complexa) react to form a sandwich complex.
Do not freeze.
▪ 2nd incubation: After addition of streptavidin-coated microparticles, the Store the Elecsys reagent kit upright in order to ensure complete
complex becomes bound to the solid phase via interaction of biotin and availability of the microparticles during automatic mixing prior to use.
streptavidin.

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Elecsys CEA
Stability: ▪ 03023141001, PC/CC‑Cups, 12 cups to prewarm ProCell M and
CleanCell M before use
unopened at 2‑8 °C up to the stated expiration date
▪ 03005712190, ProbeWash M, 12 x 70 mL cleaning solution for run
after opening at 2‑8 °C 12 weeks finalization and rinsing during reagent change
on MODULAR ANALYTICS E170, 6 weeks ▪ 12102137001, AssayTip/AssayCup, 48 magazines x 84 reaction
cobas e 411 and cobas e 601 cups or pipette tips, waste bags
analyzers ▪ 03023150001, WasteLiner, waste bags
on cobas e 602 analyzer 4 weeks ▪ 03027651001, SysClean Adapter M
Specimen collection and preparation Additional materials for all analyzers:
Only the specimens listed below were tested and found acceptable. ▪ 11298500160, ISE Cleaning Solution/Elecsys SysClean,
Serum collected using standard sampling tubes or tubes containing 5 x 100 mL system cleaning solution
separating gel. Assay
Li‑heparin, K2‑EDTA and K3‑EDTA plasma. For optimum performance of the assay follow the directions given in this
Plasma tubes containing separating gel can be used. document for the analyzer concerned. Refer to the appropriate operator’s
manual for analyzer‑specific assay instructions.
Criterion: Slope 0.9‑1.1 + coefficient of correlation ≥ 0.95.
Resuspension of the microparticles takes place automatically prior to use.
Stable for 7 days at 20‑25 °C, 14 days at 2‑8 °C, 6 months at Read in the test-specific parameters via the reagent barcode. If in
‑20 °C (± 5 °C). The samples may be frozen 3 times. exceptional cases the barcode cannot be read, enter the 15-digit sequence
The sample types listed were tested with a selection of sample collection of numbers.
tubes that were commercially available at the time of testing, i.e. not all Bring the cooled reagents to approximately 20 °C and place on the reagent
available tubes of all manufacturers were tested. Sample collection systems disk (20 °C) of the analyzer. Avoid foam formation. The system
from various manufacturers may contain differing materials which could automatically regulates the temperature of the reagents and the
affect the test results in some cases. When processing samples in primary opening/closing of the bottles.
tubes (sample collection systems), follow the instructions of the tube
manufacturer. Calibration
Centrifuge samples containing precipitates before performing the assay. Traceability: This method has been standardized against the 1st IRP WHO
Reference Standard 73/601.
Do not use heat‑inactivated samples.
Every Elecsys reagent set has a barcoded label containing specific
Do not use samples and controls stabilized with azide. information for calibration of the particular reagent lot. The predefined
Ensure the samples, calibrators and controls are at 20‑25 °C prior to master curve is adapted to the analyzer using the relevant CalSet.
measurement. Calibration frequency: Calibration must be performed once per reagent lot
Due to possible evaporation effects, samples, calibrators and controls on using fresh reagent (i.e. not more than 24 hours since the reagent kit was
the analyzers should be analyzed/measured within 2 hours. registered on the analyzer).
Sample stability claims were established by experimental data by the Calibration interval may be extended based on acceptable verification of
manufacturer or based on reference literature and only for the calibration by the laboratory.
temperatures/time frames as stated in the method sheet. It is the Renewed calibration is recommended as follows:
responsibility of the individual laboratory to use all available references
and/or its own studies to determine specific stability criteria for its ▪ after 1 month (28 days) when using the same reagent lot
laboratory. ▪ after 7 days (when using the same reagent kit on the analyzer)
Materials provided ▪ as required: e.g. quality control findings outside the defined limits
See “Reagents – working solutions” section for reagents.
Quality control
Materials required (but not provided) For quality control, use PreciControl Tumor Marker or PreciControl
▪ 11731645322, CEA CalSet, for 4 x 1.0 mL Universal.
▪ 11776452160, PreciControl Tumor Marker, for 4 x 3.0 mL In addition, other suitable control material can be used.
11731416160, PreciControl Universal, for 4 x 3.0 mL Controls for the various concentration ranges should be run individually at
▪ 03183971122, Diluent Universal, 2 x 36 mL sample diluent least once every 24 hours when the test is in use, once per reagent kit, and
following each calibration.
▪ General laboratory equipment The control intervals and limits should be adapted to each laboratory’s
▪ MODULAR ANALYTICS E170 or cobas e analyzer individual requirements. Values obtained should fall within the defined
Additional materials for cobas e 411 analyzer: limits. Each laboratory should establish corrective measures to be taken if
values fall outside the defined limits.
▪ 11662988122, ProCell, 6 x 380 mL system buffer
If necessary, repeat the measurement of the samples concerned.
▪ 11662970122, CleanCell, 6 x 380 mL measuring cell cleaning Follow the applicable government regulations and local guidelines for
solution quality control.
▪ 11930346122, Elecsys SysWash, 1 x 500 mL washwater additive
Calculation
▪ 11933159001, Adapter for SysClean The analyzer automatically calculates the analyte concentration of each
▪ 11706802001, AssayCup, 60 x 60 reaction cups sample (either in ng/mL or µg/L).
▪ 11706799001, AssayTip, 30 x 120 pipette tips 1 ng/mL CEA corresponds to 16.9 mIU/mL.
▪ 11800507001, Clean‑Liner Limitations - interference
Additional materials for MODULAR ANALYTICS E170, cobas e 601 and The assay is unaffected by icterus (bilirubin < 1129 µmol/L or < 66 mg/dL),
cobas e 602 analyzers: hemolysis (Hb < 1.4 mmol/L or < 2.2 g/dL), lipemia (Intralipid < 1500 mg/dL)
and biotin (< 491 nmol/L or < 120 ng/mL).
▪ 04880340190, ProCell M, 2 x 2 L system buffer
Criterion: Recovery within ± 10 % of initial value.
▪ 04880293190, CleanCell M, 2 x 2 L measuring cell cleaning
solution Samples should not be taken from patients receiving therapy with high
biotin doses (i.e. > 5 mg/day) until at least 8 hours following the last biotin
administration.

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Elecsys CEA
No interference was observed from rheumatoid factors up to a cobas e 411 analyzer
concentration of 1500 IU/mL.
Intermediate
There is no high‑dose hook effect at CEA concentrations up to Repeatability
precision
200000 ng/mL.
In vitro tests were performed on 26 commonly used pharmaceuticals. No Mean SD CV SD CV
Sample
interference with the assay was found. ng/mL ng/mL % ng/mL %
Drug interferences are measured based on recommendations given in CLSI Human serum 1 2.2 0.11 5.0 0.12 5.4
guidelines EP07 and EP37 and other published literature. Effects of
concentrations exceeding these recommendations have not been Human serum 2 19.6 0.32 1.6 0.44 2.3
characterized. Human serum 3 528 6.82 1.3 10.6 2.0
In rare cases, interference due to extremely high titers of antibodies to PreciControl TMb)1 4.9 0.12 2.5 0.18 3.6
analyte‑specific antibodies, streptavidin or ruthenium can occur. These
effects are minimized by suitable test design. PreciControl TM2 34.1 0.58 1.7 1.02 3.0
For diagnostic purposes, the results should always be assessed in b) TM = Tumor Marker
conjunction with the patient’s medical history, clinical examination and other
findings. MODULAR ANALYTICS E170, cobas e 601 and cobas e 602 analyzers
Limits and ranges Repeatability Intermediate precision
Measuring range Mean SD CV Mean SD CV
0.200‑1000 ng/mL (defined by the lower detection limit and the maximum of Sample
ng/mL ng/mL % ng/mL ng/mL %
the master curve). Values below the lower detection limit are reported as
< 0.200 ng/mL. Values above the measuring range are reported as Human serum 1 3.32 0.05 1.3 3.90 0.18 4.7
> 1000 ng/mL (or up to 50000 ng/mL for 50‑fold diluted samples). Human serum 2 225 2.53 1.0 252 11.6 4.6
Lower detection limit of the test
Human serum 3 626 11.8 1.9 699 34.8 5.0
Lower detection limit: 0.200 ng/mL
PreciControl TM1 4.38 0.10 2.5 4.74 0.24 5.1
The Lower Detection Limit represents the lowest measurable analyte level
that can be distinguished from zero. It is calculated as the value lying two PreciControl TM2 33.8 0.73 2.0 34.9 1.71 4.9
standard deviations above that of the lowest standard (master calibrator,
standard 1 + 2 SD, repeatability study, n = 21). Method comparison
Dilution A comparison of the Elecsys CEA assay (y) with the Enzymun‑Test CEA
method (x) using clinical samples gave the following correlations:
Samples with CEA concentrations above the measuring range can be
diluted with Diluent Universal. The recommended dilution is 1:50 (either Number of samples measured: 108
automatically by the analyzers or manually). The concentration of the
diluted sample must be > 20 ng/mL. Passing/Bablok10 Linear regression
After manual dilution, multiply the result by the dilution factor. y = 0.91x + 0.06 y = 0.90x + 0.04
After dilution by the analyzers, the software automatically takes the dilution τ = 0.913 r = 0.992
into account when calculating the sample concentration. The sample concentrations were between 0.7 and 52 ng/mL.
Expected values Analytical specificity
Studies with the Elecsys CEA assay were performed on 352 healthy For the monoclonal antibodies used, the following cross‑reactivities were
subjects. The following results were obtained: found:
Non-smokers NCA1 < 0.7 %, NCA2 72 %.
Smokers
All subjects (past/never No cross‑reactivity with AFP and α1‑acid glycoprotein.
(current)
smokers) No investigations into possible cross‑reactivity with glycoproteins from the
Age (years) 20‑69 40‑69 20‑69 40‑69 20‑69 40‑69 lungs and liver have been performed.
95thpercentile References
4.7 5.2 3.8 5.0 5.5 6.5 1 Thompson J, Zimmermann W. The carcinoembryonic antigen gene
(ng/mL)
family: structure, expression and evolution. Tumour Biol
N 352 203 242 154 110 49 1988;9(2-3):63-83.
Each laboratory should investigate the transferability of the expected values 2 Hammarström S. The carcinoembryonic antigen (CEA) family:
to its own patient population and if necessary determine its own reference structures, suggested functions and expression in normal and
ranges. malignant tissues. Semin Cancer Biol 1999;9(2):67-81.
Specific performance data 3 Thompson JA. Molecular cloning and expression of carcinoembryonic
Representative performance data on the analyzers are given below. antigen gene family members. Tumor Biol 1995;16:10-16.
Results obtained in individual laboratories may differ. 4 Ballesta AM, Molina R, Filella X, et al. Carcinoembryonic Antigen in
Staging and Follow-up of Patients with Solid Tumors. Tumor Biol
Precision 1995;16:32-41.
Precision was determined using Elecsys reagents, pooled human sera and
controls in a modified protocol (EP5‑A) of the CLSI (Clinical and Laboratory 5 Ruibal Morell A. CEA serum levels in nonneoplastic disease. Int J Biol
Standards Institute): 6 times daily for 10 days (n = 60); repeatability on Markers 1992;7(3):160-166.
MODULAR ANALYTICS E170 analyzer, n = 21. The following results were 6 Fukuda I, Yamakado M, Kiyose H. Influence of Smoking on Serum
obtained: Carcinoembryonic Antigen Levels in Subjects Who Underwent
Multiphasic Health Testing and Services. J Med Syst 1998;22(2):89-93.
7 Bormer OP, Thrane-Steen K. Epitope group specificity of six
immunoassays for carcino-embryonic antigen. Tumor Biol
1991;12:9-15.

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Elecsys CEA
8 Occupational Safety and Health Standards: Bloodborne pathogens.
(29 CFR Part 1910.1030). Fed. Register.
9 Directive 2000/54/EC of the European Parliament and Council of
18 September 2000 on the protection of workers from risks related to
exposure to biological agents at work.
10 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, the product
information and the Method Sheets of all necessary components (if
available in your country).
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
Analyzers/Instruments on which reagents can be used
Reagent
Calibrator
Volume after reconstitution or mixing
GTIN Global Trade Item Number

FOR US CUSTOMERS ONLY: LIMITED WARRANTY

Roche Diagnostics warrants that this product will meet the specifications
stated in the labeling when used in accordance with such labeling and will
be free from defects in material and workmanship until the expiration date
printed on the label. THIS LIMITED WARRANTY IS IN LIEU OF ANY
OTHER WARRANTY, EXPRESS OR IMPLIED, INCLUDING ANY IMPLIED
WARRANTY OF MERCHANTABILITY OR FITNESS FOR PARTICULAR
PURPOSE. IN NO EVENT SHALL ROCHE DIAGNOSTICS BE LIABLE
FOR INCIDENTAL, INDIRECT, SPECIAL OR CONSEQUENTIAL
DAMAGES.
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INTRALIPID is a trademark of Fresenius Kabi AB.
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.
© 2020, Roche Diagnostics

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www.roche.com
Distribution in USA by:
Roche Diagnostics, Indianapolis, IN
US Customer Technical Support 1-800-428-2336

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