Elecsys Anti-HBc IgM

cobas e 402
07026811190 07026811500 300
cobas e 801

English ▪ Results are determined automatically by the software by comparing the

electrochemiluminescence signal obtained from the reaction product of
System information the sample with the signal of the cutoff value previously obtained by
Short name ACN (application code number) calibration.
a) Tris(2,2'‑bipyridyl)ruthenium(II)‑complex (Ru(bpy) )
AHBCIGM 10040
Reagents - working solutions
Intended use The cobas e pack (M, R1, R2) is labeled as AHBCIGM.
Immunoassay for the in vitro qualitative determination of IgM antibodies to
the hepatitis B core antigen in human serum and plasma. M Streptavidin-coated microparticles, 1 bottle, 16 mL:
The electrochemiluminescence immunoassay “ECLIA” is intended for use Streptavidin-coated microparticles 0.72 mg/mL; preservative.
on cobas e immunoassay analyzers. R1 Pretreatment anti‑HBc IgM, 1 bottle, 18.8 mL:
Summary Sample pretreatment reagent: Anti‑human‑Fdγ‑antibody (sheep)
Hepatitis B virus (HBV) is transmitted by percutaneous or mucosal exposure > 0.05 mg/mL; phosphate buffer 100 mmol/L, pH 7.4; preservative.
to infected blood and various body fluids including saliva, menstrual, R2 Anti-h-IgM-Ab~biotin; HBcAg~Ru(bpy) , 1 bottle, 18.8 mL:
vaginal, and seminal fluids.1 The majority of adult patients recover
completely from their HBV infection, but up to 10 % of them become Biotinylated monoclonal anti‑h‑IgM antibody (mouse) > 600 ng/mL;
asymptomatic carriers or develop chronic hepatitis which may lead to HBcAg (E. coli, rDNA), labeled with ruthenium complex > 200 ng/mL;
cirrhosis and/or liver cancer.2,3 Despite immunization, HBV is still prevalent phosphate buffer 100 mmol/L, pH 7.4; preservative.
worldwide with approximately 250 million chronically infected patients and a
serious threat to blood transfusion safety, especially in highly endemic AHBCIGM Cal1 Negative calibrator 1, 1 bottle of 1.0 mL:
countries.4,5 Human serum; preservative.
Serological diagnosis of HBV infection involves the detection of HBV
specific antigens and/or antibodies to identify different phases of the AHBCIGM Cal2 Positive calibrator 2, 1 bottle of 1.0 mL:
HBV infection to determine whether a patient has acute or chronic Anti‑HBc IgM (human) > 100 PEI‑U/mLb) in human
HBV infection, is susceptible to infection, or is immune to HBV as a result of serum; preservative.
prior infection or vaccination.6,7 In addition, some of these HBV markers are
routinely used in patient and donor screening.7 b) Paul‑Ehrlich‑Institute units

HBV consists of an external envelope (HBsAg) and an inner core. The Precautions and warnings
hepatitis B core antigen (HBcAg) is a highly immunogenic nucleocapside For in vitro diagnostic use.
protein.8 During an infection with HBV, antibodies to HBcAg appear shortly Exercise the normal precautions required for handling all laboratory
after the onset of HBV infection and can usually be detected in serum soon reagents.
after the appearance of HBsAg. Free HBcAg or core particles are not Disposal of all waste material should be in accordance with local guidelines.
detectable in serum.6 Safety data sheet available for professional user on request.
Anti‑HBc IgM antibodies are one of the first serologic markers of HBV This kit contains components classified as follows in accordance with the
infection and usually persist for up to 6 months, being then replaced by Regulation (EC) No. 1272/2008:
anti‑HBc IgG antibodies.1,8,9 High titers of anti‑HBc IgM are detected during
acute hepatitis B infection while low titers can be detected during chronic
hepatitis B infection (CHB), and moderately high titers can occur in cases of
CHB associated with viral replication and inflammatory activity.6,10 Tests to
detect anti‑HBc IgM antibodies are used, in conjunction with HBsAg
determinations, to identify acute HBV infections.8 However, what
occasionally appears to be an acute hepatitis B can occur in undiagnosed Warning
CHB carriers and additional tests are required to differentiate between H317 May cause an allergic skin reaction.
chronic and acute infection.9
Prevention:
Test principle
µ‑Capture test principle. Total duration of assay: 18 minutes. P261 Avoid breathing dust/fume/gas/mist/vapours/spray.
▪ 1st incubation: Pretreatment of 6 µL of sample (automatically prediluted
1:400 with Diluent Universal) with anti‑Fdγ reagent to block specific IgG. P272 Contaminated work clothing should not be allowed out of
the workplace.
▪ 2nd incubation: Biotinylated monoclonal h‑IgM‑specific antibodies,
HBcAg labeled with a ruthenium complexa) and streptavidin-coated P280 Wear protective gloves.
microparticles are added to the pretreated sample. Anti‑HBc IgM
antibodies present in the sample react with the ruthenium‑labeled Response:
HBcAg and the biotinylated anti‑h‑IgM to form a sandwich complex
which becomes bound to the solid phase via interaction of biotin and P333 + P313 If skin irritation or rash occurs: Get medical
streptavidin. advice/attention.
▪ The reaction mixture is aspirated into the measuring cell where the
microparticles are magnetically captured onto the surface of the P362 + P364 Take off contaminated clothing and wash it before reuse.
electrode. Unbound substances are then removed with ProCell II M. Disposal:
Application of a voltage to the electrode then induces chemiluminescent
emission which is measured by a photomultiplier. P501 Dispose of contents/container to an approved waste
disposal plant.
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590
All human material should be considered potentially infectious.
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Elecsys Anti-HBc IgM
The negative calibrator (AHBCIGM Cal1) has been prepared exclusively from Ensure the samples and calibrators are at 20‑25 °C prior to measurement.
the blood of donors tested individually and shown to be free from HBsAg and Due to possible evaporation effects, samples and calibrators on the
antibodies to HCV and HIV. analyzers should be analyzed/measured within 2 hours.
The testing methods used assays approved by the FDA or cleared in The performance of the Elecsys Anti‑HBc IgM assay has not been
compliance with the European Directive 98/79/EC, Annex II, List A. established with cadaveric samples or body fluids other than serum or
Positive calibrator (AHBCIGM Cal2): Materials of human origin were tested plasma.
for HIV and hepatitis C. The findings were negative. The serum containing
anti‑HBc IgM was inactivated using β‑propiolactone and UV‑radiation. Materials provided
See “Reagents – working solutions” section for reagents.
However, as no inactivation or testing method can rule out the potential risk
of infection with absolute certainty, the material should be handled with the ▪ 2 x 6 bottle labels
same level of care as a patient specimen. In the event of exposure, the Materials required (but not provided)
directives of the responsible health authorities should be followed.11,12
Avoid foam formation in all reagents and sample types (specimens, ▪ 11876333122, PreciControl Anti‑HBc IgM, 16 x 1.0 mL
calibrators and controls). ▪ 11776576322, CalSet Vials, 2 x 56 empty snap-cap bottles
Reagent handling ▪ 07299001190, Diluent Universal, 45.2 mL sample diluent
The reagents (M, R1, R2) in the kit are ready-for-use and are supplied in ▪ General laboratory equipment
cobas e packs.
▪ cobas e analyzer
Calibrators Additional materials for cobas e 402 and cobas e 801 analyzers:
The calibrators are supplied ready‑for‑use in bottles compatible with the
system. ▪ 06908799190, ProCell II M, 2 x 2 L system solution
Unless the entire volume is necessary for calibration on the analyzer, transfer ▪ 04880293190, CleanCell M, 2 x 2 L measuring cell cleaning
aliquots of the ready‑for‑use calibrators into empty snap-cap bottles (CalSet solution
Vials). Attach the supplied labels to these additional bottles. Store the ▪ 07485409001, Reservoir Cup, 8 cups to supply ProCell II M and
aliquots at 2‑8 °C for later use. CleanCell M
Perform only one calibration procedure per aliquot. ▪ 06908853190, PreClean II M, 2 x 2 L wash solution
All information required for correct operation is available via the cobas link. ▪ 05694302001, Assay Tip/Assay Cup tray, 6 magazines
Storage and stability x 6 magazine stacks x 105 assay tips and 105 assay cups, 3 wasteliners
Store at 2‑8 °C. ▪ 07485425001, Liquid Flow Cleaning Cup, 2 adaptor cups to supply
Do not freeze. ISE Cleaning Solution/Elecsys SysClean for Liquid Flow Cleaning
Detection Unit
Store the cobas e pack upright in order to ensure complete availability of
the microparticles during automatic mixing prior to use. ▪ 07485433001, PreWash Liquid Flow Cleaning Cup, 1 adaptor cup
to supply ISE Cleaning Solution/Elecsys SysClean for Liquid Flow
Stability of the cobas e pack: Cleaning PreWash Unit
unopened at 2‑8 °C up to the stated expiration date ▪ 11298500316, ISE Cleaning Solution/Elecsys SysClean,
5 x 100 mL system cleaning solution
on the analyzers 16 weeks
Assay
Stability of the calibrators: For optimum performance of the assay follow the directions given in this
document for the analyzer concerned. Refer to the appropriate operator’s
unopened at 2‑8 °C up to the stated expiration date manual for analyzer‑specific assay instructions.
after opening at 2‑8 °C 16 weeks Resuspension of the microparticles takes place automatically prior to use.
on the analyzers at 20‑25 °C use only once Place the cooled (stored at 2‑8 °C) cobas e pack on the reagent manager.
Avoid foam formation. The system automatically regulates the temperature
Store calibrators upright in order to prevent the calibrator solution from of the reagents and the opening/closing of the cobas e pack.
adhering to the snap‑cap. Calibrators:
Specimen collection and preparation Place the calibrators in the sample zone.
Only the specimens listed below were tested and found acceptable. Read in all the information necessary for calibrating the assay.
Serum collected using standard sampling tubes or tubes containing
separating gel. Calibration
Traceability: This method has been standardized against the “HBc
Li‑heparin, Na‑heparin, K2‑EDTA, K3‑EDTA, ACD, CPD, CP2D, CPDA and Reference Serum 84 (anti‑HBc IgM)” of the Paul‑Ehrlich‑Institut, Langen
Na‑citrate plasma. (Germany). For the Elecsys Anti‑HBc IgM assay, the cutoff (cutoff
Plasma tubes containing separating gel can be used. index 1.0) was set to approximately 100 PEI‑U/mL.13
Criterion: Correct assignment of positive and negative samples. Samples Calibration frequency: Calibration must be performed once per reagent lot
with a COI (cutoff index) ≥ 1.0: ± 20 % recovery; samples with a COI < 1.0: using AHBCIGM Cal1, AHBCIGM Cal2 and fresh reagent (i.e. not more
± 0.20 recovery. than 24 hours since the cobas e pack was registered on the analyzer).
Stable for 7 days at 20‑25 °C, 14 days at 2‑8 °C, 3 months at Calibration interval may be extended based on acceptable verification of
‑20 °C (± 5 °C). The samples may be frozen 5 times. calibration by the laboratory.
The sample types listed were tested with a selection of sample collection Renewed calibration is recommended as follows:
tubes or systems that were commercially available at the time of testing, i.e.
not all available tubes of all manufacturers were tested. Sample collection ▪ after 8 weeks when using the same reagent lot
systems from various manufacturers may contain differing materials which ▪ after 28 days when using the same cobas e pack on the analyzer
could affect the test results in some cases. When processing samples in
primary tubes (sample collection systems), follow the instructions of the ▪ as required: e.g. quality control findings outside the defined limits
tube/collection system manufacturer. Range for the electrochemiluminescence signals (counts) for the
calibrators:
Centrifuge samples containing precipitates and thawed samples before Negative calibrator (AHBCIGM Cal1): 400‑3500
performing the assay. Positive calibrator (AHBCIGM Cal2): 18000‑130000
Do not use samples and controls stabilized with azide.

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Elecsys Anti-HBc IgM
Quality control Drug Concentration tested
For quality control, use PreciControl Anti‑HBc IgM. mg/L
Controls for the various concentration ranges should be run individually at Peginterferon alfa-2b ≤ 0.036
least once every 24 hours when the test is in use, once per cobas e pack,
and following each calibration. Lamivudine ≤ 300
The control intervals and limits should be adapted to each laboratory’s Adefovir ≤ 10
individual requirements. Values obtained should fall within the defined limits.
Each laboratory should establish corrective measures to be taken if values Entecavir ≤1
fall outside the defined limits. Telbivudine ≤ 600
If necessary, repeat the measurement of the samples concerned. Tenofovir ≤ 245
Follow the applicable government regulations and local guidelines for quality
control. In rare cases, interference due to extremely high titers of antibodies to
immunological components, streptavidin and ruthenium can occur.
Calculation For diagnostic purposes, the results should always be assessed in
The analyzer automatically calculates the cutoff based on the measurement conjunction with the patient’s medical history, clinical examination and other
of AHBCIGM Cal1 and AHBCIGM Cal2. findings.
The result of a sample is given either as reactive or non-reactive as well as in Dilution
the form of a cutoff index (signal sample/cutoff).
Use Diluent Universal for automatic sample predilution.
Interpretation of the results
Expected values
Numeric result Result message Interpretation/ For the Elecsys Anti‑HBc IgM assay, the cutoff (cutoff index 1.0) was set to
further steps approximately 100 PEI‑U/mL. In acute HBV infections the anti‑HBc IgM
level is generally far above this limit. After recovery from hepatitis B the
COI < 1.0 Non-reactive Negative for anti‑HBc IgM anti‑HBc IgM levels are below this. Chronic hepatitis B can produce values
COI ≥ 1.0 Reactive Positive for anti‑HBc IgM in the vicinity of the cutoff.
Note: According to the recommendations of the Paul‑Ehrlich‑Institut, Specific performance data
Langen (Germany), an equivocal range should be allowed for the Representative performance data on the analyzers are given below.
assessment of results from anti‑HBc IgM tests. For the Elecsys Results obtained in individual laboratories may differ.
Anti‑HBc IgM assay the equivocal cutoff index range is 0.9‑1.1. Precision
Limitations - interference Precision was determined using Elecsys reagents, samples and controls in
The effect of the following endogenous substances and pharmaceutical a protocol (EP05‑A3) of the CLSI (Clinical and Laboratory Standards
compounds on assay performance was tested. Interferences were tested Institute): 2 runs per day in duplicate each for 21 days (n = 84). The
up to the listed concentrations and no impact on results was observed. following results were obtained:
Endogenous substances cobas e 402 and cobas e 801 analyzers
Compound Concentration tested Repeatabilityc) Intermediate
Bilirubin ≤ 428 µmol/L or ≤ 25 mg/dL precisiond)

Hemoglobin ≤ 0.621 mmol/L or ≤ 1000 mg/dL Sample Mean SD CV SD CV

COI COI % COI %
Intralipid ≤ 1500 mg/dL
HSe), negative 0.069 0.001 1.6 0.001 1.9
Biotin ≤ 410 nmol/L or ≤ 100 ng/mL
HS, weakly positive 1.03 0.031 3.0 0.034 3.3
Rheumatoid factors ≤ 1200 IU/mL
HS, positive 2.06 0.063 3.1 0.070 3.4
Albumin ≤ 7 g/dL
PCf) Anti-HBc IgM 1 0.071 0.001 1.7 0.001 2.0
IgG ≤ 7 g/dL
PC Anti-HBc IgM 2 1.39 0.037 2.6 0.045 3.2
IgA ≤ 1.6 g/dL
c) Repeatability = within-run precision
Samples with a COI ≥ 1.0: ± 20 % recovery; samples with a COI < 1.0: d) Intermediate precision = between-run precision
± 0.20 recovery.
e) HS = human serum
Samples should not be taken from patients receiving therapy with high f) PC = PreciControl
biotin doses (i.e. > 5 mg/day) until at least 8 hours following the last biotin
administration. Analytical specificity
As with many µ‑capture assays an interference with unspecific human IgM 131 samples containing potentially interfering substances were tested with
is observed. Increasing amounts of unspecific human IgM may lead to a the Elecsys Anti‑HBc IgM assay comprising specimens:
decrease in the recovery of positive samples with the Elecsys Anti‑HBc IgM ▪ containing antibodies against HAV, HCV, HIV, HSV, Rubella, CMV,
assay. EBV, Toxoplasma gondii, Treponema pallidum
Pharmaceutical substances ▪ positive for E. coli
In vitro tests were performed on 16 commonly used pharmaceuticals. No
interference with the assay was found. ▪ after vaccination against HAV and HBV
In addition, the following special drugs used in hepatitis B therapy were ▪ non-viral induced liver diseases
tested. No interference with the assay was found. ▪ autoimmune diseases (ANA and SLE)
Special drugs No false reactive results were found with the Elecsys Anti‑HBc IgM assay
resulting in a specificity of 100 %.
Drug Concentration tested
Cutoff sensitivity
mg/L
Approximately 100 PEI‑U/mL for the Elecsys Anti‑HBc IgM assay. Assays
Peginterferon alfa-2a ≤ 0.036 of other manufacturers may be set differently.

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Elecsys Anti-HBc IgM
Clinical sensitivity Contents of kit
245 samples from patients with different stages of HBV infection (acute, late Analyzers/Instruments on which reagents can be used
acute/early recovery) were tested and were consistently found to be reactive
using the Elecsys Anti‑HBc IgM assay and a comparison test. Reagent
Clinical specificity Calibrator
Samples from blood donors, from routine and from hospitalized patients Volume for reconstitution
which had not been specifically selected were used to determine the
specificity. GTIN Global Trade Item Number
Group Number Number Specificity COBAS, COBAS E, ELECSYS and PRECICONTROL are trademarks of Roche. INTRALIPID is a trademark of
tested reactive % Fresenius Kabi AB.
All other product names and trademarks are the property of their respective owners.
Blood donors 1000 0 100 Additions, deletions or changes are indicated by a change bar in the margin.
Samples from 1000 1g) 100 © 2021, Roche Diagnostics
routine and from
hospitalized patients
g) 1 out of 1000 samples from routine or from hospitalized patients was found discrepantly
reactive with the comparison assay. It could be confirmed as true negative.
References
1 World Health Organization (WHO), 2015. Hepatitis B. Fact sheet
N°204. Available at:
http://www.who.int/mediacentre/factsheets/fs204/en/
2 Kim do Y, Han KH. Epidemiology and Surveillance of Hepatocellular
Carcinoma. Liver Cancer 2012;1(1):2-14.
3 Liang TJ. Hepatitis B: The Virus and Disease. Hepatology 2009;49(5
Suppl):S13-21.
4 Schweitzer A, Horn J, Mikolajczyk RT, et al. Estimations of worldwide
prevalence of chronic hepatitis B virus infection: a systematic review of
data published between 1965 and 2013. Lancet
2015;386(10003):1546-1555
5 Song Y, Bian Y, Petzold M, et al. Prevalence and Trend of Major
Transfusion-Transmissible Infections among Blood Donors in Western
China, 2005 through 2010. PLoS One. 2014 Apr 8;9(4):e94528.
6 Elgouhari HM, Abu-Rajab Tamini TI, Carey W. Hepatitis B virus
infection: understanding its epidemiology, course, and diagnosis. Cleve
Clin J Med 2008;75:881-889.
7 World Health Organization (WHO), 2009. Screening Donated Blood for
Transfusion-Transmissible Infections. Recommendations. Available at:
at http://www.who.int/bloodsafety/ScreeningTTI.pdf (last access
January, 2016).
8 Seeger C, Zoulim F, Mason WS. Hepadnaviruses. In: Fields Virology,
Knipe DM, Howley PM (eds), 2007 5th edition, Lippincott Williams and
Wilkins, Philadelphia, USA. Chapter 76, pp2977-3029.
9 Liaw YF, Chu CM. Hepatitis B virus infection. Lancet
2009;373:582–592.
10 Caspari G, Gerlick WH. The serologic markers of hepatitis B virus
infection – proper selection and standardized interpretation. Clin Lab
2007;53:335-343.
11 Occupational Safety and Health Standards: Bloodborne pathogens.
(29 CFR Part 1910.1030). Fed. Register.
12 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.
13 Hadziyannis JS, Hadziyannis AS, Dourakis S, et al. Clinical
Significance of Quantitative Anti-HBc IgM assay in Acute and Chronic
HBV Infection. Hepato Gastroenterol 1993;40:588-592.
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).
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.
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):

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