08086630500V3.

Elecsys Anti-HAV II
cobas e 411
08086630190 08086630500 100 cobas e 601
cobas e 602

English ▪ Results are determined via a calibration curve which is instrument-

specifically generated by 2‑point calibration and a master curve provided
System information via the reagent barcode or e‑barcode.
For cobas e 411 analyzer: test number 1570 a) Tris(2,2'-bipyridyl)ruthenium(II)-complex (Ru(bpy) )
For cobas e 601 and cobas e 602 analyzers: Application Code
Number 469 Reagents - working solutions
Intended use The reagent rackpack (M, R1, R2) is labeled as AHAV 2.
Immunoassay for the in vitro qualitative detection of total antibodies (IgG M Streptavidin-coated microparticles (transparent cap), 1 bottle, 6.5 mL:
and IgM) to the hepatitis A virus (HAV) in human serum and plasma. The Streptavidin-coated microparticles 0.72 mg/mL; preservative.
assay is used as an aid to detect a past or existing hepatitis A infection or
used to determine the presence of antibody response to HAV in vaccine R1 HAV Ag (gray cap), 1 bottle, 10 mL:
recipients. HAV Ag (cell culture) 28 U/mL (Roche units); TRIS buffer 20 mmol/L,
The electrochemiluminescence immunoassay “ECLIA” is intended for use pH 7.2; preservative.
on cobas e immunoassay analyzers.
R2 Anti-HAV Ab~biotin; anti-HAV Ab~Ru(bpy) (black cap), 1 bottle,
Summary 9 mL:
The hepatitis A virus (HAV) is a non-enveloped single stranded RNA-virus Biotinylated monoclonal anti‑HAV antibody (mouse) 0.25 µg/mL;
that belongs to the family of picornaviruses. To date, just one human monoclonal anti‑HAV antibody (mouse) labeled with ruthenium
serotype and 6 genotypes have been described, 3 of which infect humans
(genotypes I, II and III).1 Initially, 7 genotypes were described, but complex 0.65 µg/mL; TRIS buffer 20 mmol/L, pH 7.2; preservative.
subsequent analyses suggest that genotypes II and VII are subtypes of
genotype II.2 The viral capsid consists of 3 major structural proteins AHAV 2 Cal1 Negative calibrator 1 (white cap), 2 bottles of 1.0 mL
(VP1‑VP3) and a fourth putative protein (VP4) that form an each:
immunodominant structure on the surface of the viral particle, which is Anti‑HAV negative human serum; preservative.
highly conserved between all genotypes. After vaccination or natural
infection, the immune response is directed against this structure.1,3 AHAV 2 Cal2 Positive calibrator 2 (black cap), 2 bottles of 1.0 mL each:
HAV is one of the most common causes of infectious jaundice and is Anti‑HAV (human) approximately 60 IU/L in human
transmitted by the fecal-oral route. HAV causes acute hepatitis and is not serum; preservative.
associated with chronic liver disease because the virus does not persist in
the organism.1,3 Precautions and warnings
For in vitro diagnostic use for health care professionals. Exercise the
Total anti‑HAV (anti‑HAV IgM and IgG) is positive at the onset of symptoms normal precautions required for handling all laboratory reagents.
and due to the presence of IgM.4 After natural infection, anti‑HAV IgG can
usually be detected early in the course of infection and remains detectable Infectious or microbial waste:
throughout a person’s lifetime conferring protection against the disease if Warning: handle waste as potentially biohazardous material. Dispose of
the organism is reinfected.4,5 waste according to accepted laboratory instructions and procedures.
Vaccines against HAV and combined vaccines against hepatitis A and B Environmental hazards:
are available today.3,4 Anti‑HAV IgG can be detected approximately Apply all relevant local disposal regulations to determine the safe disposal.
2 weeks after vaccination against HAV. In the case of complete Safety data sheet available for professional user on request.
immunization, protection usually lasts for many years. To define a This kit contains components classified as follows in accordance with the
protective antibody response, clinical vaccine studies typically used Regulation (EC) No. 1272/2008:
anti‑HAV levels of > 20 IU/L, while some studies have used levels of
> 10 IU/L.5,6,7 A positive anti‑HAV result indicates immune protection.
However, after vaccination, persons who are anti‑HAV negative (< 20 IU/L)
might nevertheless have protective levels of antibody. The absolute lower
limit of anti‑HAV required to prevent HAV infection has not been defined. In
vitro studies using cell-culture-derived virus indicate that low levels of
antibody (e.g. < 20 IU/L) can be neutralizing.8 Warning
Assays to detect anti‑HAV antibodies are used to determine an existing or
past HAV infection or to observe the immune response after HAV H317 May cause an allergic skin reaction.
vaccination.1 Prevention:
Test principle
P261 Avoid breathing dust/fume/gas/mist/vapours/spray.
Competition principle. Total duration of assay: 18 minutes.
▪ 1st incubation: 20 µL of sample; the anti‑HAV in the sample binds the P272 Contaminated work clothing should not be allowed out of
added HAV antigen. the workplace.
▪ 2nd incubation: After addition of biotinylated antibodies and ruthenium
complexa)‑labeled antibodies specific for HAV antigen, together with P280 Wear protective gloves.
streptavidin-coated microparticles, the still-free binding sites on the HAV Response:
antigens become occupied. The entire complex becomes bound to the
solid phase via interaction of biotin and streptavidin. P333 + P313 If skin irritation or rash occurs: Get medical
▪ The reaction mixture is aspirated into the measuring cell where the advice/attention.
microparticles are magnetically captured onto the surface of the
electrode. Unbound substances are then removed with P362 + P364 Take off contaminated clothing and wash it before reuse.
ProCell/ProCell M. Application of a voltage to the electrode then induces
chemiluminescent emission which is measured by a photomultiplier. Disposal:

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Elecsys Anti-HAV II
P501 Dispose of contents/container to an approved waste Li‑heparin, Na‑heparin, K2‑EDTA, K3‑EDTA, ACD, CPD, CP2D, CPDA and
disposal plant. Na‑citrate plasma.
Product safety labeling follows EU GHS guidance. Plasma tubes containing separating gel can be used.
Contact phone: all countries: +49-621-7590 Criterion: Correct assignment of positive and negative samples. Samples
with a COI (cutoff index) > 1.0: ± 20 % recovery compared to serum
All human material should be considered potentially infectious. All products reference; samples with a COI ≤ 1.0: ± 0.20 COI recovery compared to
derived from human blood are prepared exclusively from the blood of serum reference.
donors tested individually and shown to be free from HBsAg and antibodies
to HCV and HIV. The testing methods use assays that have been approved Stable for 6 days at 20‑25 °C, 14 days at 2‑8 °C, 3 months at
by the FDA or that are in compliance with the legal rules applicable to ‑20 °C (± 5 °C). The samples may be frozen 5 times.
placing in vitro diagnostic medical devices for human use on the market in The sample types listed were tested with a selection of sample collection
the European Union. tubes that were commercially available at the time of testing, i.e. not all
However, as no testing method can rule out the potential risk of infection available tubes of all manufacturers were tested. Sample collection systems
with absolute certainty, the material should be handled with the same level from various manufacturers may contain differing materials which could
of care as a patient specimen. In the event of exposure, the directives of the affect the test results in some cases. When processing samples in primary
responsible health authorities should be followed.9,10 tubes (sample collection systems), follow the instructions of the tube
manufacturer.
Avoid foam formation in all reagents and sample types (specimens,
calibrators and controls). Centrifuge samples containing precipitates and thawed samples before
performing the assay.
Reagent handling Do not use heat‑inactivated samples.
The reagents in the kit are ready‑for‑use and are supplied in bottles Do not use samples and controls stabilized with azide.
compatible with the system.
Ensure the samples, calibrators and controls are at 20‑25 °C prior to
Calibrators measurement.
cobas e 411 analyzer: The calibrators should only be left on the analyzer Due to possible evaporation effects, samples and calibrators on the
during calibration at 20‑25 °C. After use, close the bottles as soon as analyzers should be analyzed/measured within 2 hours.
possible and store upright at 2‑8 °C.
The performance of the Elecsys Anti‑HAV II assay has not been
Due to possible evaporation effects, not more than 5 calibration procedures established with cadaveric samples or body fluids other than serum and
per bottle set should be performed. plasma.
cobas e 601 and cobas e 602 analyzers: Unless the entire volume is
necessary for calibration on the analyzers, transfer aliquots of the ready-for- Materials provided
use calibrators into empty snap-cap bottles (CalSet Vials). Attach the ▪ See “Reagents – working solutions” section for reagents.
supplied labels to these additional bottles. Store the aliquots at 2‑8 °C for
later use. ▪ 2 x 6 bottle labels
Perform only one calibration procedure per aliquot. Materials required (but not provided)
All information required for correct operation is read in from the respective ▪ 08086672190, PreciControl Anti‑HAV II, for 8 x 1.3 mL
reagent barcodes. ▪ 11776576322, CalSet Vials, 2 x 56 empty bottles with snap-caps
Please note: Both the vial labels, and the additional labels (if available) ▪ General laboratory equipment
contain 2 different barcodes. The barcode between the yellow markers is
for cobas 8000 systems only. If using a cobas 8000 system, please turn ▪ cobas e analyzer
the vial cap 180° into the correct position so the barcode can be read by the Additional materials for the cobas e 411 analyzer:
system. Place the vial on the instrument as usual.
▪ 11662988122, ProCell, 6 x 380 mL system buffer
Storage and stability ▪ 11662970122, CleanCell, 6 x 380 mL measuring cell cleaning
Store at 2‑8 °C. solution
Do not freeze. ▪ 11930346122, Elecsys SysWash, 1 x 500 mL washwater additive
Store the Elecsys reagent kit upright in order to ensure complete ▪ 11933159001, Adapter for SysClean
availability of the microparticles during automatic mixing prior to use.
▪ 11706802001, AssayCup, 60 x 60 reaction cups
Stability of the reagent rackpack ▪ 11706799001, AssayTip, 30 x 120 pipette tips
unopened at 2‑8 °C up to the stated expiration date ▪ 11800507001, Clean‑Liner
after opening at 2‑8 °C 8 weeks Additional materials for cobas e 601 and cobas e 602 analyzers:
on the analyzers 8 weeks ▪ 04880340190, ProCell M, 2 x 2 L system buffer
▪ 04880293190, CleanCell M, 2 x 2 L measuring cell cleaning
Stability of the calibrators solution
unopened at 2‑8 °C up to the stated expiration date ▪ 03023141001, PC/CC‑Cups, 12 cups to prewarm ProCell M and
after opening at 2‑8 °C 8 weeks CleanCell M before use
▪ 03005712190, ProbeWash M, 12 x 70 mL cleaning solution for run
on cobas e 411 at 20‑25 °C up to 6 hours finalization and rinsing during reagent change
on cobas e 601 and cobas e 602 use once only ▪ 03004899190, PreClean M, 5 x 600 mL detection cleaning solution
at 20‑25 °C
▪ 12102137001, AssayTip/AssayCup, 48 magazines x 84 reaction
Store calibrators upright in order to prevent the calibrator solution from cups or pipette tips, waste bags
adhering to the snap‑cap. ▪ 03023150001, WasteLiner, waste bags
Specimen collection and preparation ▪ 03027651001, SysClean Adapter M
Only the specimens listed below were tested and found acceptable. Additional materials for all analyzers:
Serum collected using standard sampling tubes or tubes containing
separating gel. ▪ 11298500316, ISE Cleaning Solution/Elecsys SysClean,
5 x 100 mL system cleaning solution

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Assay Limitations - interference
For optimum performance of the assay follow the directions given in this The effect of the following endogenous substances and pharmaceutical
document for the analyzer concerned. Refer to the appropriate operator’s compounds on assay performance was tested. Interferences were tested
manual for analyzer‑specific assay instructions. up to the listed concentrations and no impact on results was observed.
Resuspension of the microparticles takes place automatically prior to use. Endogenous substances
Read in the test-specific parameters via the reagent barcode. If in
exceptional cases the barcode cannot be read, enter the 15-digit sequence Compound Concentration tested
of numbers.
Bilirubin ≤ 1129 µmol/L or ≤ 66 mg/dL
cobas e 601 and cobas e 602 analyzers: PreClean M solution is
necessary. Hemoglobin ≤ 0.621 mmol/L or ≤ 1000 mg/dL
Bring the cooled reagents to approximately 20 °C and place on the reagent Intralipid ≤ 2000 mg/dL
disk (20 °C) of the analyzer. Avoid foam formation. The system
automatically regulates the temperature of the reagents and the Biotin ≤ 573 nmol/L or ≤ 140 ng/mL
opening/closing of the bottles. Rheumatoid factors ≤ 1400 IU/mL
Place the calibrators in the sample zone. IgG ≤ 7.0 g/dL
All the information necessary for calibrating the assay is automatically read
into the analyzer. IgA ≤ 1.6 g/dL
After calibration has been performed, store the calibrators at 2‑8 °C or IgM ≤ 1.0 g/dL
discard (cobas e 601 and cobas e 602 analyzers).
Criterion:
Calibration Samples > 1.0 COI ± 20 % recovery
Traceability: The Elecsys Anti‑HAV II assay is traceable to the “Second Samples ≤ 1.0 COI ± 0.20 COI recovery
International Standard for Anti‑Hepatitis A, immunoglobulin, human", NIBSC Samples should not be taken from patients receiving therapy with high
code 97/646 of the NIBSC (National Institute for Biological Standards and biotin doses (i.e. > 5 mg/day) until at least 8 hours following the last biotin
Control) via method comparison to the first generation Elecsys Anti‑HAV administration.
assay as reference. Pharmaceutical substances
Calibration frequency: Calibration must be performed once per reagent lot In vitro tests were performed on 18 commonly used pharmaceuticals. No
using AHAV 2 Cal1, AHAV 2 Cal2 and fresh reagent (i.e. not more than interference with the assay was found.
24 hours since the reagent kit was registered on the analyzer). In rare cases, interference due to extremely high titers of antibodies to
Calibration interval may be extended based on acceptable verification of analyte‑specific antibodies, streptavidin or ruthenium can occur. These
calibration by the laboratory. effects are minimized by suitable test design.
Renewed calibration is recommended as follows: For diagnostic purposes, the results should always be assessed in
▪ after 1 month (28 days) when using the same reagent lot conjunction with the patient’s medical history, clinical examination and other
findings.
▪ after 7 days (when using the same reagent kit on the analyzer)
Specific performance data
▪ as required: e.g. quality control findings outside the defined limits Representative performance data on the analyzers are given below.
Quality control Results obtained in individual laboratories may differ.
For quality control, use PreciControl Anti‑HAV II. Precision
Controls for the various concentration ranges should be run individually at Precision was determined using Elecsys reagents, samples and controls in
least once every 24 hours when the test is in use, once per reagent kit, and a protocol (EP05‑A3) of the CLSI (Clinical and Laboratory Standards
following each calibration. Institute): 2 runs per day in duplicate each for 21 days (n = 84). The
The control intervals and limits should be adapted to each laboratory’s following results were obtained:
individual requirements. Values obtained should fall within the defined
limits. Each laboratory should establish corrective measures to be taken if cobas e 411 analyzer
values fall outside the defined limits. Repeatability Intermediate
If necessary, repeat the measurement of the samples concerned. precision
Follow the applicable government regulations and local guidelines for Sample Mean SD CV SD CV
quality control.
COI COI % COI %
Calculation
Human serum 1 1.37 0.012 0.9 0.018 1.3
The analyzer automatically calculates the cutoff based on the measurement
of AHAV 2 Cal1 and AHAV 2 Cal2. Human serum 2 1.11 0.013 1.2 0.016 1.5
The result of a sample is given either as reactive or non‑reactive as well as Human serum 3 0.940 0.011 1.2 0.016 1.7
in the form of a cutoff‑index (COI; signal sample/cutoff).
Human serum 4 0.661 0.012 1.9 0.021 3.2
Interpretation of the results
Human serum 5 0.010 0.0001 1.4 0.0002 2.2
Numeric result Result message Interpretation PCb) Anti-HAV II 1 1.30 0.013 1.0 0.016 1.3
COI > 1.0 Non-reactive Negative for HAV-specific PC Anti-HAV II 2 0.332 0.005 1.7 0.011 3.2
antibodies
b) PC = PreciControl
COI ≤ 1.0 Reactive Positive for HAV-specific
antibodies cobas e 601 and cobas e 602 analyzers
The cutoff of the Elecsys Anti‑HAV II assay was determined in a large Repeatability Intermediate
cohort of blood donors and hospitalized patients using the first generation precision
Elecsys Anti‑HAV assay, which has a cutoff of 20 IU/L, as the reference.
The cutoff of the Elecsys Anti‑HAV II assay thus corresponds to 20 IU/L. Sample Mean SD CV SD CV
COI COI % COI %
COI values ≤ 1.0 indicate an existing or past hepatitis A infection or the
presence of anti‑HAV antibodies after hepatitis A vaccination. Human serum 1 1.42 0.016 1.1 0.028 2.0

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Elecsys Anti-HAV II
cobas e 601 and cobas e 602 analyzers 5 Tilzey, AJ, Palmer SJ, Barrow S, et al. Clinical trial with inactivated
hepatitis A vaccine and recommendations for its use. BMJ
Repeatability Intermediate 1992;304:1272-1276.
precision
6 Briem H, Safary A. Immunogenicity and Safety in Adults of Hepatitis A
Sample Mean SD CV SD CV Virus Vaccine Administered as a Single Dose With a Booster 6 Months
COI COI % COI % Later. J Med Virol 1994;44:443-445.
Human serum 2 1.15 0.012 1.1 0.022 1.9 7 Ambrosch F, Finkel B, Herzog C, et al. Rapid Antibody Response after
Vaccination with a Virosomal Hepatitis A Vaccine. Infection
Human serum 3 0.955 0.009 0.9 0.022 2.3 2004;32:149-152.
Human serum 4 0.665 0.009 1.3 0.020 2.9 8 Lemon SM, Binn LN. Serum Neutralizing Antibody Response to
Human serum 5 0.006 0.0002 3.0 0.0002 3.3 Hepatitis A Virus. J Infect Dis 1983;148:1033-1039.
PCb) Anti-HAV II 1 1.30 0.015 1.1 0.024 1.8 9 Occupational Safety and Health Standards: Bloodborne pathogens.
(29 CFR Part 1910.1030). Fed. Register.
PC Anti-HAV II 2 0.339 0.005 1.5 0.009 2.7 10 Directive 2000/54/EC of the European Parliament and Council of
Analytical specificity 18 September 2000 on the protection of workers from risks related to
exposure to biological agents at work.
No cross-reactions with HBV, HCV, HIV, CMV, EBV, HSV, Toxoplasma
gondii, Rubella, Mumps/Rubeola, Parvovirus B19 and Treponema pallidum For further information, please refer to the appropriate operator’s manual for
were observed. the analyzer concerned, the respective application sheets, the product
Measurements were performed on each of the pathogens listed above information and the Method Sheets of all necessary components (if
using a total of 120 human serum or plasma which were positive for available in your country).
antibodies to the above-mentioned pathogens or contained autoantibodies A point (period/stop) is always used in this Method Sheet as the decimal
(ANA). separator to mark the border between the integral and the fractional parts of
Clinical data a decimal numeral. Separators for thousands are not used.
In the clinical studies, conducted to assess the relative sensitivity and Any serious incident that has occurred in relation to the device shall be
relative specificity of the assay, samples from various international sources reported to the manufacturer and the competent authority of the Member
were used. State in which the user and/or the patient is established.
The Summary of Safety & Performance Report can be found here:
Clinical sensitivity https://ec.europa.eu/tools/eudamed
The relative sensitivity was found to be 100 % in samples from subjects
vaccinated against HAV, acutely infected subjects and subjects who had Symbols
recovered from a natural HAV infection. 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
N Sensitivity 95 % CIc) (2-sided) definition of symbols used):
% %
Contents of kit
Subjects vaccinated 238 100 98.45-100
against hepatitis A Analyzers/Instruments on which reagents can be used
Subjects with acute 234 100 98.44-100 Reagent
hepatitis A infection Calibrator
Subjects recovered from 256 100 98.57-100 Volume after reconstitution or mixing
hepatitis A infection
GTIN Global Trade Item Number
c) CI = confidence interval
COBAS, COBAS E, ELECSYS and PRECICONTROL are trademarks of Roche. INTRALIPID is a trademark of
Clinical specificity Fresenius Kabi AB.
A total of 874 confirmed anti‑HAV negative samples from subjects with All other product names and trademarks are the property of their respective owners.
routine requests for anti‑HAV testing and 580 samples confirmed anti‑HAV Additions, deletions or changes are indicated by a change bar in the margin.
negative from blood donors were tested with the Elecsys Anti‑HAV II assay. © 2020, Roche Diagnostics

Nd) Specificity 95 % CI (2-sided)

% %
Blood donors 577 99.48 98.49-99.89 Roche Diagnostics GmbH, Sandhofer Strasse 116, D-68305 Mannheim
www.roche.com
Subjects with routine 871 99.66 99.00-99.93
+800 5505 6606
request for anti‑HAV
testing
d) Number of subjects with a negative Elecsys Anti‑HAV II test result
References
1 Hollinger FB, Emerson SU. Hepatitis A virus. In: Fields Virology, Knipe
DM, Howley PM (eds), 2007 5th edition, Lippincott Williams and
Wilkins, Philadelphia, USA. Chapter 27, pp911-947.
2 Lu L, Ching KZ, de Paula SV, et al. Characterization of the complete
genomic sequence of genotype II hepatitis A virus (CF53/Berne
isolate). J Gen Virol 2004;855:2943-2952.
3 Martin A, Lemon SM. Hepatitis A virus: from discovery to vaccines.
Hepatology 2006 Feb;43(2 Suppl 1):S164-172.
4 Wasley A, Fiore A, Bell BP. Hepatitis A in the era of vaccination.
Epidemiol Rev 2006;28:101-111.

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