SYSTEM

E
Anti-HBc
7C17
34-3095/R4

Anti-HBc
Customer Service
United States: 1-877-4ABBOTT
International: Call your Abbott Representative

This package insert must be read carefully prior to product use. Package insert instructions must be followed accordingly. Reliability of
assay results cannot be guaranteed if there are any deviations from the instructions in this package insert.

Note Changes Highlighted

Key to symbols used

List Number Lot Number

For In Vitro Diagnostic Use

Control Number

Store at 2-8°C
Reaction Vessels
©2003, Abbott Laboratories

Sample Cups
Expiration Date

Septum
Serial Number

Reagent Lot
Replacement Caps

Legal Manufacturer
Consult instructions for use

Authorized Representative

See REAGENTS section for a full explanation of symbols used in reagent component naming.

ABBOTT
Max-Planck-Ring 2
65205 Wiesbaden
Germany
+49-6122-580

Abbott Laboratories
Diagnostics Division
Abbott Park, IL 60064 USA Printed in USA

7C17-1C-00_Eng_ReIn.p65 1 12/5/2003, 10:08 AM

Color: PMS 329 CVC

SIZE: 8 1/2 x 11
FILE: Alms
EDITOR: Ann Marie
PUBLISHER: Craig
 NAME
ARCHITECT Anti-HBc
INTENDED USE
The ARCHITECT Anti-HBc assay is a Chemiluminescent
Microparticle Immunoassay (CMIA) for the qualitative detection of
antibody to Hepatitis B core antigen (anti-HBc) in human serum and
plasma. The ARCHITECT Anti-HBc assay is intended to be used as
a screen for blood and plasma to prevent transmission of
hepatitis B virus (HBV) to recipients of blood and blood components
and as an aid in the diagnosis of HBV infection.
SUMMARY AND EXPLANATION OF TEST
The ARCHITECT Anti-HBc assay utilizes microparticles coated with
recombinant Hepatitis B Virus Core Antigen (rHBcAg) for the
detection of anti-HBc. Anti-HBc determinations can be used to
monitor the progress of hepatitis B viral infection. Anti-HBc is found
in serum shortly after the appearance of Hepatitis B Surface Antigen
(HBsAg) in acute hepatitis B infections. It will persist after the
disappearance of HBsAg and before the appearance of detectable
antibody to HBsAg (anti-HBs).1-7 In the absence of information about
any other hepatitis B virus (HBV) markers, it must be considered
that an individual with detectable levels of anti-HBc may be actively
infected with HBV or that the infection may have resolved, leaving
the person immune.8 Anti-HBc may be the only serological marker
of hepatitis B viral infection and potentially infectious blood.9-15
The presence of anti-HBc does not differentiate between acute or
chronic hepatitis B infection.
BIOLOGICAL PRINCIPLES OF THE PROCEDURE
The ARCHITECT Anti-HBc assay is a two-step immunoassay, using
Chemiluminescent Microparticle Immunoassay (CMIA) technology,
for the qualitative detection of anti-HBc in human serum and plasma.
In the first step, sample, assay diluent, and HBc antigen coated
paramagnetic microparticles are combined. Anti-HBc present in the
sample binds to the HBc antigen coated microparticles. After
washing, anti-human acridinium-labeled conjugate is added in the
second step. Following another wash cycle, Pre-Trigger and Trigger
Solutions are added to the reaction vessel (RV). The resulting
chemiluminescent reaction is measured as relative light units
(RLUs). A direct relationship exists between the amount of
anti-HBc in the sample and the RLUs detected by the
ARCHITECT i* optical system.
The presence or absence of anti-HBc in the specimen is determined
by comparing the chemiluminescent signal in the reaction to the
cutoff signal determined from a previous calibration. If the
chemiluminescent signal in the specimen is greater than or equal to
the cutoff signal, the specimen is considered reactive for anti-HBc.
For additional information on system and assay technology, refer to
the ARCHITECT System Operations Manual, Section 3.
*i = immunoassay
REAGENTS
Reagent Kit, 100/500 Tests
NOTE: Some kit sizes are not available in all countries; please
contact your local distributor.
ARCHITECT Anti-HBc Reagent Kit (7C17)
• 1 or 4 Bottle(s) (6.6 mL per 100 test bottle/
27.0 mL per 500 test bottle) Hepatitis B Core (E. coli,
Recombinant) Antigen Coated Microparticles in MOPSO buffer
with protein stabilizers. Minimum concentration: 0.08% solids.
Preservative: Antimicrobial Agents.
• 1 or 4 Bottle(s) (5.9 mL per 100 test bottle/
26.3 mL per 500 test bottle) Anti-Human (Mouse, Monoclonal)
Acridinium-Labeled Conjugate in MES buffer with protein
stabilizers. Minimum concentration: 0.049 µg/mL. Preservative:
Antimicrobial Agents.
7C17-1C-00_Eng_ReIn.p65 2 12/5/2003, 10:08 AM
• 1 or 4 Bottle(s) (10.0 mL per 100 test bottle/
50.9 mL per 500 test bottle) Anti-HBc Assay Diluent containing
protein stabilizers in MOPSO buffer. Preservative: Antimicrobial
Agents.
Other Reagents
ARCHITECT i Pre-Trigger Solution
• Pre-Trigger Solution containing
1.32% (w/v) hydrogen peroxide.
ARCHITECT i Trigger Solution
• Trigger Solution containing 0.35N
sodium hydroxide.
ARCHITECT i Wash Buffer
• Wash Buffer containing phosphate buffered
saline solution. Preservative: Antimicrobial Agent.
WARNINGS AND PRECAUTIONS
• For In Vitro Diagnostic Use.
• Package insert instructions must be followed. Reliability of
assay results cannot be guaranteed if there are any
deviations from the instructions in this package insert.
Safety Precautions
• CAUTION: All human sourced materials should be
considered potentially infectious. It is recommended that
human specimens be handled in accordance with the OSHA
Standard on Bloodborne Pathogens.16 Biosafety Level 217
or other appropriate biosafety practices18,19 should be used
for materials that contain or are suspected of containing
infectious agents.
• These precautions include, but are not limited to the following:
1. Wear gloves when handling specimens or reagents.
2. Do not pipette by mouth.
3. Do not eat, drink, smoke, apply cosmetics, or handle
contact lenses in areas where these materials are handled.
4. Clean and disinfect all spills of specimens or reagents
using a tuberculocidal disinfectant such as 0.5% sodium
hypochlorite, or other suitable disinfectant.20,21
5. Decontaminate and dispose of all specimens, reagents and
other potentially contaminated materials in accordance with
local, state and federal regulations.22,23
• ARCHITECT i Trigger Solution contains sodium hydroxide
(NaOH) and is classified per applicable European Community
(EC) Directives as: Irritant (Xi). The following are the appropriate
Risk (R) and Safety (S) phrases.
R41 Risk of serious damage to eyes.
S25 Avoid contact with eyes.
S26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S35 This material and its container must be disposed
of in a safe way.
S36/39 Wear suitable protective clothing and eye/face
protection.
S46 If swallowed, seek medical advice immediately
and show this container or label.
Information for European customers: For product not classified as
dangerous per European Directive 1999/45/EC - Safety data sheet
available for professional user on request.
• For a detailed discussion of safety precautions during system
operation, refer to the ARCHITECT System Operations Manual,
Section 8.
Handling Precautions
• Do not use reagent kits beyond the expiration date.
• Do not pool reagents within a reagent kit or between reagent
kits.
 • Prior to loading the ARCHITECT Anti-HBc Reagent Kit on the
system for the first time, the microparticle bottle requires mixing
to resuspend microparticles that may have settled during
shipment. For microparticle mixing instructions, refer to the
PROCEDURE, Assay Procedure section of this package insert.
• Septums MUST be used to prevent reagent evaporation and
contamination, and to ensure reagent integrity. Reliability
of assay results cannot be guaranteed if septums are not
used according to the instructions in this package insert.
• To avoid contamination, wear clean gloves when placing a
septum on an uncapped reagent bottle.
• When handling conjugate vials, change gloves that have
contacted human plasma/sera, since introduction of human
IgG will result in a neutralized conjugate.
• Prior to placing the septum on an uncapped reagent bottle,
squeeze the septum in half to confirm that the slits are open. If
the slits appear sealed, continue to gently squeeze the septum
to open the slits.
• Once a septum has been placed on an open reagent bottle, do
not invert the bottle as this will result in reagent leakage and
may compromise assay results.
• Over time, residual liquids may dry on the septum surface. These
are typically dried salts and have no effect on assay efficacy.
• For a detailed discussion of handling precautions during system
operation, refer to the ARCHITECT System Operations Manual,
Section 7.
Storage Instructions
• The ARCHITECT Anti-HBc Reagent Kit, Calibrators,
and Controls must be stored at 2-8°C in an upright position and
may be used immediately after removal from 2-8°C storage.
• When stored and handled as directed, reagents are stable until
the expiration date.
• The ARCHITECT Anti-HBc Reagent Kit may be stored on-board
the ARCHITECT i System for a maximum of 30 days. After
30 days, the reagent kit must be discarded. For information on
tracking on-board time, refer to the ARCHITECT System
Operations Manual, Section 5.
• Reagents may be stored on or off the ARCHITECT i System. If
reagents are removed from the system, store them at 2-8°C (with
septums and replacement caps) in an upright position. For
reagents stored off the system, it is recommended they be stored
in their original trays and boxes to ensure they remain upright. If
the microparticle bottle does not remain upright (with a
septum installed) while in refrigerated storage off the system,
the reagent kit must be discarded. After reagents are removed
from the system, you must initiate a scan to update the on-board
stability timer.
Indications of Reagent Deterioration
When a control value is out of the specified range, it may indicate
deterioration of the reagents or errors in technique. Associated test
results are invalid and will require retesting. Assay recalibration may
be necessary. For troubleshooting information, refer to the
ARCHITECT System Operations Manual, Section 10.
INSTRUMENT PROCEDURE
• The ARCHITECT Anti-HBc assay file must be installed on the
ARCHITECT i System from the ARCHITECT i Assay CD-ROM
prior to performing the assay. For detailed information on assay
file installation and viewing and editing assay parameters, refer
to the ARCHITECT System Operations Manual, Section 2.
• For information on printing assay parameters, refer to the
ARCHITECT System Operations Manual, Section 5.
• For a detailed description of system procedures, refer to the
ARCHITECT System Operations Manual.
7C17-1C-00_Eng_ReIn.p65 3 12/5/2003, 10:08 AM
SPECIMEN COLLECTION AND PREPARATION FOR
ANALYSIS
• Human serum (including serum collected in serum separator
tubes) or plasma collected in potassium EDTA, sodium citrate,
sodium heparin, lithium heparin, ACD, CPDA-1, CP2D, CPD,
and potassium oxalate may be used in the ARCHITECT Anti-HBc
assay. Other anticoagulants have not been validated for use with
the ARCHITECT Anti-HBc assay. Follow the collection tube
manufacturer’s instructions for processing serum or plasma.
• The ARCHITECT i System does not provide the capability to
verify specimen type. It is the responsibility of the operator to
verify the correct specimen types are used in the ARCHITECT
Anti-HBc assay.
• Performance has not been established using cadaver specimens
or body fluids other than human serum or plasma.
• Use caution when handling patient specimens to prevent cross
contamination. Use of disposable pipettes or pipette tips is
recommended.
• This assay was designed and validated for use with human serum
or plasma from individual patient and donor specimens. Pooled
specimens must not be used since the accuracy of their test
results has not been validated.
• Do not use heat-inactivated specimens.
• Do not use grossly hemolyzed specimens.
• For optimal results, inspect all samples for bubbles. Remove
bubbles with an applicator stick prior to analysis. Use a new
applicator stick for each sample to prevent cross contamination.
• For optimal results, serum and plasma specimens should
be free of fibrin, red blood cells, or other particulate matter.
Such specimens may give inconsistent results and must be
transferred to a centrifuge tube and centrifuged at least
10,000 RCF (Relative Centrifugal Force) for 10 minutes.
• Ensure that complete clot formation in serum specimens has
taken place prior to centrifugation. Some specimens, especially
those from patients receiving anticoagulant or thrombolytic
therapy may exhibit increased clotting time. If the specimen is
centrifuged before a complete clot forms, the presence of fibrin
may cause erroneous results.
• Gravity separation is not sufficient for specimen preparation.
Specimens must be separated from clots or red blood cells
using centrifugation as recommended by the tube
manufacturer.
• Specimens may be stored on or off the clot or red blood cells for
up to 7 days at 2-8°C.
• If testing will be delayed more than 7 days, remove serum or
plasma from the clot, serum separator, or red blood cells, and
store frozen (-20°C or colder).
• Specimens must be mixed THOROUGHLY after thawing by
LOW speed vortexing. Specimens containing particulate
matter must be centrifuged prior to running the assay.
• Centrifuged specimens with a lipid layer on the top must be
transferred to a sample cup or secondary tube. Care must be
taken to transfer only the clarified specimen without the lipemic
material.
• No qualitative differences were observed between experimental
controls and the 24 nonreactive or 24 spiked reactive specimens
subjected to 6 freeze-thaw cycles; however, multiple freeze-thaw
cycles should be avoided.
• Specimens from heparinized patients may be partially coagulated
and erroneous results could occur due to the presence of fibrin.
To prevent this phenomenon, draw the specimen prior to heparin
therapy.
 • When shipped, specimens must be packaged and labeled in
compliance with applicable state, federal, and international
regulations covering the transport of specimens and infectious
substances. Specimens may be shipped ambient, at 2-8°C (wet
ice), or -20°C or colder (dry ice). Do not exceed the storage time
limitations listed above. Prior to shipment, it is recommended
that specimens be removed from the clot, serum separator, or
red blood cells.
• No qualitative performance differences were observed between
experimental controls and the 23 nonreactive or 23 spiked
reactive specimens tested with elevated levels of bilirubin
(< 20 mg/dL), hemoglobin (< 500 mg/dL), triglycerides
(< 3,000 mg/dL), or protein (< 12 g/dL).
• No qualitative performance differences were observed between
experimental controls and 24 nonreactive or 24 spiked reactive
specimens tested with red blood cells at < 0.4% v/v.
PROCEDURE
Materials Provided:
• 7C17 ARCHITECT Anti-HBc Reagent Kit
Materials Required but not Provided:
• ARCHITECT i System
• 7C17-01 ARCHITECT Anti-HBc Calibrator 1
• 7C17-10 ARCHITECT Anti-HBc Controls
• ARCHITECT i
• ARCHITECT i
• ARCHITECT i
• ARCHITECT i
• ARCHITECT i
• ARCHITECT i
• ARCHITECT i
• Pipettes or pipette tips (optional) to deliver the volumes specified
on the patient or control order screen.
• For information on materials required for maintenance
procedures, refer to the ARCHITECT System Operations
Manual, Section 9.
Assay Procedure
• Before loading the ARCHITECT Anti-HBc Reagent Kit on the
system for the first time, the microparticle bottle requires mixing
to resuspend microparticles that may have settled during
shipment:
• Invert the microparticle bottle 30 times.
• Visually inspect the bottle to ensure microparticles are
resuspended. If microparticles are still adhered to the bottle,
continue to invert the bottle until the microparticles have been
completely resuspended.
• Once the microparticles have been resuspended, remove
and discard the cap. Wearing clean gloves, remove a septum
from the bag. Squeeze the septum in half to confirm that the
slits are open. Carefully snap the septum onto the top of the
bottle.
• If the microparticles do not resuspend, DO NOT USE;
contact your local Abbott representative.
• Order calibration, if necessary.
• For information on ordering calibrations, refer to the
ARCHITECT System Operations Manual, Section 6.
• Order tests.
• For information on ordering patient specimens, calibrators,
controls, and general operating procedures, refer to the
ARCHITECT System Operations Manual, Section 5.
• Load the ARCHITECT Anti-HBc Reagent Kit on the
ARCHITECT i System. Verify that all necessary reagents are
present. Ensure that septums are present on all reagent bottles.
7C17-1C-00_Eng_ReIn.p65 4 12/5/2003, 10:08 AM
• The minimum sample cup volume is calculated by the system
and is printed on the Orderlist report. No more than 10 replicates
may be sampled from the same sample cup. To minimize the
effects of evaporation verify adequate sample cup volume is
present prior to running the test.
• Priority: 75 µL for the first Anti-HBc test plus 25 µL for each
additional Anti-HBc test from the same sample cup.
• 울 3 hours on-board: 150 µL for the first Anti-HBc test plus
25 µL for each additional Anti-HBc test from the same sample
cup.
• > 3 hours on-board: additional sample volume is required.
Refer to the ARCHITECT System Operations Manual,
Section 5 for information on sample evaporation and volumes.
• If using primary or aliquot tubes, use the sample gauge to
ensure sufficient patient specimen is present.
• ARCHITECT Anti-HBc Calibrator and Controls should be
mixed by gentle inversion prior to use. To obtain the
recommended volume requirements for the ARCHITECT
Anti-HBc Calibrator and Controls, hold the bottles vertically,
and dispense 5 drops of the Calibrator or 4 drops of each
Control into each respective sample cup.
• Load samples.
• For information on loading samples, refer to the ARCHITECT
System Operations Manual, Section 5.
• Press RUN. The ARCHITECT i System performs the following
functions:
• Moves the sample to the aspiration point.
• Loads a reaction vessel (RV) into the process path.
• Aspirates and transfers sample into the RV.
• Advances the RV one position and transfers assay diluent
and microparticles into the RV.
• Mixes, incubates, and washes the reaction mixture.
• Adds conjugate to the RV.
• Mixes, incubates, and washes the reaction mixture.
• Adds Pre-Trigger and Trigger Solutions.
• Measures chemiluminescent emission to detect the presence
of anti-HBc in the sample.
• Aspirates contents of RV to liquid waste and unloads RV to
solid waste.
• Calculates the result.
• For optimal performance, it is important to follow the routine
maintenance procedures defined in the ARCHITECT System
Operations Manual, Section 9. If your laboratory requires more
frequent maintenance, follow those procedures.
Specimen Dilution Procedures
Specimens cannot be diluted for the ARCHITECT Anti-HBc assay.
Calibration
• To perform an ARCHITECT Anti-HBc calibration, test 3 replicates
of Anti-HBc Calibrator 1. A single sample of all levels of Anti-HBc
controls must be tested to evaluate the assay calibration. Ensure
that assay control values are within the ranges specified in the
Control package insert. Calibrators should be priority loaded.
• Once an ARCHITECT Anti-HBc calibration is accepted and
stored, all subsequent samples may be tested without further
calibration unless:
• A reagent kit with a new lot number is used
• Controls are out of range
• For detailed information on how to perform an assay calibration,
refer to the ARCHITECT System Operations Manual, Section 6.
QUALITY CONTROL PROCEDURES
NOTE: It is recommended that the ARCHITECT Anti-HBc Positive
Control and Negative Control be run in order to verify the calibration.
The recommended control requirement for the ARCHITECT
Anti-HBc assay is a single sample of each control tested once every
24 hours each day of use. If the quality control procedures in your
 laboratory require more frequent use of controls to verify test results, TABLE I
follow your laboratory-specific procedures. Ensure that assay control ARCHITECT Anti-HBc Precision
values are within the ranges specified in the Control package insert. Panel Total No. Grand Mean Intra-assay Inter-assaya Totalb
Members Replicates (S/CO) SD %CV SD %CV SD %CV
Verification of Assay Claims
For protocols to verify package insert claims, refer to the ARCHITECT 1 120 0.25 0.020 7.7 0.026 10.4 0.056 22.1
2 120 0.92 0.041 4.4 0.046 5.0 0.072 7.8
System Operations Manual, Appendix B. The ARCHITECT Anti-HBc
3 120 1.70 0.079 4.7 0.082 4.9 0.111 6.5
assay belongs to method group 5. 4 120 6.39 0.663 10.4 0.691 10.8 0.728 11.4
5 120 8.98 0.390 4.3 0.440 4.9 0.507 5.6
RESULTS 6 120 11.50 0.720 6.3 0.733 6.4 0.799 6.9
The ARCHITECT i System calculates the Anti-HBc Calibrator 1 mean Positive Control 120 1.68 0.074 4.4 0.081 4.8 0.110 6.6

chemiluminescent signal from 3 Anti-HBc Calibrator 1 replicates and a Inter-assay variability contains intra-assay variability.
stores the result. b Total variability contains intra-assay, inter-assay, inter-lot, and inter-site variability.

Calculation
The ARCHITECT Anti-HBc assay calculates a result based on
S/CO.
• Cutoff Calculation: Calibrator Mean RLU value x 1.1 = Cutoff
RLU
• S/CO = Sample RLU/Cutoff RLU
Interpretation of Results
• Specimens with S/CO values < 1.00 are considered nonreactive
by the ARCHITECT Anti-HBc assay and need not be tested
further.
• Specimens with S/CO values > 1.00 are considered reactive by
the ARCHITECT Anti-HBc assay.
• All initially reactive specimens should be retested in duplicate. If
both retest values are nonreactive, the specimen must be
considered nonreactive for anti-HBc. If either of the retest values
is reactive, the specimen must be considered repeatedly reactive
for anti-HBc by the criteria of ARCHITECT Anti-HBc.
NOTE: For details on configuring the ARCHITECT i System to use
Grayzone Interpretations, refer to the ARCHITECT System
Operations Manual, Section 2, subsection Assay Settings, Configure
assay parameters dialog window - Interpretation.
Flags
• Some results may contain information in the Flags field. For a
description of the flags that may appear in this field, refer to the
ARCHITECT System Operations Manual, Section 5.
LIMITATIONS OF THE PROCEDURE
Specificity
A total of 2709 serum and plasma specimens from volunteer whole
blood donors, a low prevalence population for HBV infection, were
evaluated by three clinical sites (Table II). The presence of anti-HBc
in ARCHITECT anti-HBc reactive specimens was supported by the
presence of other HBV markers including HBsAg, IgM anti-HBc,
anti-HBc, anti-HBe, and HBV DNA. The initial and repeat reactive
rates were 0.85% (23/2709) and 0.81% (22/2709), respectively.
There were a total of 22 repeatedly reactive specimens of which 13
were positive, 1 was indeterminate, and 8 were negative following
supplemental testing.
Twenty-seven of 334 specimens obtained from hospital patients were
repeatedly reactive of which 26 were positive and 1 was negative
following supplemental testing. In 50 plasma specimens from
matched serum and plasma pairs, 1 specimen was repeatedly
reactive and was positive following supplemental testing. In
190 specimens from individuals with medical conditions unrelated
to HBV infection and specimens containing potentially interfering
substances, 15 specimens were repeatedly reactive of which 7 were
positive and 8 were negative following supplemental testing.
TABLE II
Reactivity of the ARCHITECT Anti-HBc Assay in Specimens from
Volunteer Whole Blood Donors, Hospital Patients, Plasma Specimens
from Matched Serum/Plasma Pairs, Individuals with Medical
Conditions Unrelated to HBV Infection, and in Specimens Containing
Potentially Interfering Substances
Number of Positive by
Supplemental Testinga
Number (% of Repeatedly
Category Tested IR (% of Total) RR (% of Total) Reactive)

• If the anti-HBc results are inconsistent with clinical evidence, Volunteer Whole Blood Donors
Serum 1347 16 (1.19%) 15 (1.11%) 10 (66.67%)
additional testing is suggested to confirm the result. Plasma 1362 7 (0.51%) 7 (0.51%) 3 (42.86%)

• For diagnostic purposes, results should be used in conjunction Total Donors 2709 23 (0.85%) 22 (0.81%) 13 (59.09%)

with patient history and other hepatitis markers for diagnosis of Hospital patients 334 28 (8.38%) 27 (8.08%) 26 (96.30%)

acute or chronic infection. Plasma Specimens from

• Samples containing particulate matter or red blood cells must be
centrifuged prior to running the assay.
• Performance has not been established using cadaver specimens
or body fluids other than human serum or plasma.
• Do not use heat-inactivated specimens.
• Specimens from heparinized patients may be partially coagulated
and erroneous results could occur due to the presence of fibrin.
To prevent this phenomenon, draw the specimen prior to heparin
therapy.
SPECIFIC PERFORMANCE CHARACTERISTICS
Precision
The precision of the ARCHITECT Anti-HBc assay was determined
during clinical studies using two reagent lots. A panel composed of
six unique members was tested in replicates of four with each reagent
lot once daily for five days at three sites. Each daily run also included
the ARCHITECT Positive Controls tested in duplicate at the beginning
and end of the run. The intra-assay and inter-assay standard
deviations (SD) and percent coefficients of variation (%CV) were
determined with a variance component analysis24 for a random
effects model25 (Table I).
Matched Serum/Plasma Pairs 50 1 (2.00%) 1 (2.00%) 1 (100.00%)
Medical Conditions Unrelated
to HBV Infection and Potentially
Interfering Substancesb 190 15 (7.89%) 15 (7.89%) 7 (46.67%)
IR = Initially Reactive; RR = Repeatedly Reactive
a A specimen was defined as anti-HBc positive if the anti-HBc (comparator method)
was reactive and one or more of the following HBV markers were detected: HBsAg,
IgM anti-HBc, anti-HBe, HBV DNA PCR, or anti-HBc (by additional ELISA methods).
b Category included the following: anti-CMV positive (10), anti-HSV (10), anti-HAV (10),
IgM anti-HAV (10), HBV vaccine recipients (10), rubella antibody positive (10),
toxoplasma antibody positive (10), E. coli infections (10), yeast infections (10), syphilis
positive (10), anti-nuclear antibody positive (10), rheumatoid factor (10), multiple
myeloma (10), pregnant females (50), and alcoholic liver disease (10).
Sensitivity
A total of 349 specimens from 182 individuals known to be positive
for total anti-HBc, 20 individuals known to be positive for IgM
anti-HBc, 18 individuals with acute HBV infection, 48 individuals with
chronic HBV infection, 14 individuals from recovered HBV infection,
and 67 individuals at increased risk for HBV infection were tested.
Of the 349 specimens, 314 (89.97%) were repeatedly reactive and
of these 314 specimens, 313 (99.68%) were positive by supplemental
testing (Table III).

7C17-1C-00_Eng_ReIn.p65 5 12/5/2003, 10:08 AM

 TABLE III
Reactivity of the ARCHITECT Anti-HBc Assay in Selected Populations
with HBV Infection and at Increased Risk for HBV Infection
ARCHITECT Anti-HBc
Assay Number of
Number Repeatedly Reactive
Category Tested (% of Total)
Preselected total anti-HBc Positive 182 182a (100.00%)
Preselected IgM anti-HBc Positive 20 20a (100.00%)
Acute HBV Infection 18 18 (100.00%)
Chronic HBV Infection 48 48 (100.00%)
Recovered HBV Infection 14 14 (100.00%)
Increased Risk for HBV Infectionb 67 32 (47.76%)
TOTAL 349 314 (89.97%)
a Specimens were tested once.
b Category included the following: intravenous drug users (34), hemophilia patients (33).
Overall Specificity and Sensitivity
Overall specificity and sensitivity were estimated from the results of
3632 serum and plasma specimens tested with the ARCHITECT
Anti-HBc assay at six clinical sites.
The overall specificity was estimated to be 99.42% (3248/3267) with
a 95% confidence interval of 99.09% to 99.65%. The overall
sensitivity was estimated to be 98.63% (360/365) with a 95%
confidence interval of 96.83 to 99.55%.
Analytical Sensitivity
The sensitivity of the ARCHITECT Anti-HBc assay was evaluated
with a six-member panel that was standardized against reference
serum from the Paul-Ehrlich-Institute (PEI). The panel was tested
with two reagent master lots at three clinical sites. The ARCHITECT
Anti-HBc assay sensitivity ranged from 0.537 to 0.542 PEI
Units/mL.
Common Technical Specifications Sensitivity and Specificity
The diagnostic sensitivity and specificity of the ARCHITECT Anti-HBc
assay were calculated according to the requirements of the Common
Technical Specifications 2002/364/EC. Additional specimens were
tested in the categories of volunteer whole blood donor (n=2362)
and preselected total anti-HBc positive (n=119) to comply with the
sample sizes required by the Specifications. The results from these
additional specimens were combined with those of the clinical
studies.
The diagnostic sensitivity was determined to be 100.00% (401/401)
with a 95% confidence interval of 99.08% to 100.00%. There were
five ARCHITECT false reactive specimens identified after testing of
the additional volunteer whole blood donor specimens. The
diagnostic specificity was determined to be 99.58% (5605/5629) with
a 95% confidence interval of 99.37% to 99.73%.
BIBLIOGRAPHY
1. Hoofnagle JH, Gerety RJ, and Barker LF. Antibody to Hepatitis
B-Virus Core in Man. Lancet 1973;ii:869–73.
2. Szmuness W, Hoofnagle JH, Stevens CE, et al. Antibody against
the Hepatitis Type B Core Antigen. Am J Epidemiol
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The following U.S. Patents are relevant to the ARCHITECT system
or its components. There are other such patents and patent
applications in the United States and worldwide.
5,468,646 5,543,524 5,545,739 5,565,570 5,669,819 5,783,699
ARCHITECT is a registered trademark of Abbott Laboratories, Abbott
Park, IL USA.
Abbott Laboratories
Diagnostics Division
Abbott Park, IL 60064 USA November, 2003