Please only refer to the current product lot insert enclosed with the kits package for execution

and reporting

0123 130210008M: 100 tests

130610008M: 050 tests

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MAGLUMI HAV IgM (CLIA)
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INTENDED USE
The kit is an in vitro chemiluminescence immunoassay for the qualitative determination of HAV IgM in human serum using the
MAGLUMI series Fully-auto chemiluminescence immunoassay analyzer (including Maglumi 600, Maglumi 800, Maglumi 1000,
Maglumi 2000, Maglumi 2000 Plus, Maglumi 4000 and Maglumi 4000 Plus).
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SUMMARY AND EXPLANATION OF THE TEST

Hepatovirus A is a species of virus in the order Picornavirales in the family Picornaviridae and is the type species of the genus
1
Hepatovirus. Humans and vertebrates serve as natural hosts . It is nonenveloped and contains a single-stranded RNA packaged
2-3
in a protein shell. There is only one serotype of the virus, but multiple genotypes exist . One serotype and seven different
genetic groups (four humans and three simians) have been described. The human genotypes are numbered I-III. Six subtypes
have been described (IA, IB, IIA, IIB, IIIA, IIIB). The simian genotypes have been numbered IV-VI. A single isolate of genotype VII
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isolated from a human has also been described. Genotype III has been isolated from both humans and owl monkeys. Most
3-5
human isolates are of genotype I. Of the type I isolates subtype IA accounts for the majority .
Hepatitis A (formerly known as infectious hepatitis) is an infectious disease of the liver caused by the hepatitis A virus (HAV).
Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop
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them, is between two and six weeks. When symptoms occur, they typically last eight weeks and may include nausea, vomiting,
diarrhea, jaundice, fever, and abdominal pain. Around 10–15% of people experience a recurrence of symptoms during the six
6-8
months after the initial infection. Acute liver failure may rarely occur, with this being more common in the elderly
Although HAV is excreted in the feces towards the end of the incubation period, specific diagnosis is made by the detection of
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HAV-specific IgM antibodies in the blood. IgM antibody is only present in the blood following an acute hepatitis A infection. It is
detectable from one to two weeks after the initial infection and persists for up to 14 weeks. The presence of IgG antibodies in the
blood means the acute stage of the illness is past and the person is immune to further infection. IgG antibodies to HAV are also
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found in the blood following vaccination, and tests for immunity to the virus are based on the detection of this antibody .
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PRINCIPLE OF THE TEST

The HAV IgM assay is an indirect chemiluminescence immunoassay.
The sample (or calibrator/control, if applicable), buffer (including goat anti-human IgG, goat anti-human IgA) and magnetic
microbeads coated with anti-human IgM antibody are mixed thoroughly and incubated at 37°C, forming anti-hIgM- antibody
complexes; perform a wash cycle. Then add free HAV Ag, and incubate to form anti-hIgM- antibody-HAV Ag complexes; and then
perform another wash cycle. Then ABEI Labeled with Anti-HAV monoclonal antibody are added, and incubate to form a
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anti-hIgM-antibody-HAV Ag-ABEI complexes. Following wash cycle, the rest unbound materials are removed, starter 1+2 are
added to initiate a flash chemiluminescent reaction.The light signal is measured by a photomultiplier within 3 seconds as relative
light units (RLUs), which is indicative of the concentration of HAV IgM present in the sample (or calibrator/control, if applicable).

KIT COMPONENTS
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Material Provided
100 tests 50 tests
Components Contents
(REF: 130210008M) (REF: 130610008M)
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Magnetic Coated with anti-human IgM antibody,

2.5 mL 2.0 mL
Microbeads containing BSA, NaN3 (<0.1%).
Low concentration of HAV IgM, containing BSA,
Calibrator Low 1.0 mL 1.0 mL
NaN3 (<0.1%).
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High concentration of HAV IgM, containing BSA,

Calibrator High 1.0 mL 1.0 mL
NaN3 (<0.1%).
Goat anti-human IgA, goat anti-human IgG,
Buffer 6.0 mL 3.0 mL
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containing BSA, NaN3 (<0.1%).

Containing Native HAV antigens and BSA, NaN3
Antigen 12.5 mL 7.0 mL
(<0.1%).
Anti-HAV monoclonal antibody labeled with
ABEI Label 12.5 mL 7.0mL
ABEI, containing BSA, NaN3 (<0.1%).

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Control 1 Containing HAV IgM and BSA, NaN3 (<0.1%). 2.0 mL 2.0 mL
Control 2 Containing HAV IgM and BSA, NaN3 (<0.1%). 2.0 mL 2.0 mL
Control 3 Containing HAV IgM and BSA, NaN3 (<0.1%). 2.0 mL 2.0 mL
All reagents are provided ready-to-use.

Accessories Required But Not Provided

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MAGLUMI Series:
Reaction Module REF: 630003
Starter 1+2 REF: 130299004M
Wash Concentrate REF: 130299005M
Light Check REF: 130299006M
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Please order accessories from Shenzhen New Industries Biomedical Engineering Co., Ltd. (SNIBE) or our authorized
representatives.

CALIBRATION
Traceability: This method has been standardized against the SNIBE internal reference substance.
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Test of assay specific calibrators allows the RLU values to adjust the assigned master curve. Results are determined via a calibration
curve which is instrument-specifically generated by 2-point calibration and a master curve(10 calibrations) provided via the reagent
Radio Frequency Identification (RFID) CHIP.
Recalibration is recommended if any of the following conditions occurs:
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 After each change of lots (Reagent or Starter 1+2).

 Every 4 weeks and/or each time a new reagent kit is used (recommended).

 After instrument service is required.

 If controls lie outside the expected range.

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 Whenever room temperature changes exceed 5° C (recommended).

QUALITY CONTROL
Follow government regulations or accreditation requirements for quality control frequency.
Internal quality control is only applicable with MAGLUMI system. For instructions for use and target value refer to HAV IgM
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(CLIA) Quality Control Information. User needs to judge results with their own standards and knowledge.
For detailed information about entering quality control values, refer to the operating instructions of MAGLUMI series Fully-auto
chemiluminescence immunoassay analyzer.
To monitor system performance and chart trends, commercially available quality control materials are required. Treat all quality
control samples the same as patient samples. A satisfactory level of performance is achieved when analyze values obtained are
within the acceptable Control Range for the system or within your range, as determined by an appropriate internal laboratory
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quality control scheme. If the quality control results do not fall within the Expected Values or within the laboratory’s established
values, do not report results. Take the following actions:
 Verify that the materials are not expired.

 Verify that required maintenance was performed.

 Verify that the assay was performed according to the instructions for use.

 Rerun the assay with fresh quality control samples.

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 If necessary, contact your local technical supporters or distributors for assistance.

SPECIMEN COLLECTION AND PREPARATION

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 Use standard sampling tubes or tubes containing separating gel. Collect blood aseptically following the universal precautions for
venipuncture.
 To ensure consistency in results, specimens must be transferred to centrifuge tubes and centrifuged at ≥10,000 RCF (Relative
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Centrifugal Force) for 15 minutes.

 Ensure that complete clot formation in 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 clotting, the presence of fibrin may cause erroneous results. Samples must be
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free of fibrin and other particulate substance.

 Do not use hemolyzed or grossly lipemic specimens as well as specimens containing particulate substance or exhibiting obvious
microbial contamination. Inspect all specimens for bubbles, and remove bubbles before analysis for optimal results.
 Avoid repeated freezing and thawing. The serum sample can be frozen and thawed for two times. Stored samples should be

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thoroughly mixed prior to use (Vortex mixer). Frozen specimens must be mixed THOROUGHLY after thawing by LOW speed
vortexing. Please ask local representative of SNIBE for more derails if you have any doubt.
 Centrifuged specimens with a lipid layer on the top must be transferred to a sample cup or secondary tube. Care should be taken
to transfer only the clarified specimen without the lipaemic material.
 All samples (patient specimens and controls) should be tested within 3 hours when placed on board the MAGLUMI System.
Refer to the SNIBE service for more details of onboard sample storage constraints.
 If testing will be delayed for more than 8 hours, serum should be removed from red blood cells or clot or separator. Specimens
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removed from the separator, red blood cells or clot may be stored up to 7 days at 2-8°C, and stored up to 6 months frozen at
-20°C or colder.
 Before shipping specimens, it is recommended that specimens be removed from the clot, red blood cells, or separator. When
shipped, specimens should be packaged and labeled in compliance with applicable state, federal and international regulations
covering the transport of clinical specimens and infectious substances. Specimens should be shipped frozen.
 The sample volume required for a single determination of HAV IgM is 10 µL.
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WARNING AND PRECAUTIONS FOR USERS


 For In Vitro Diagnostic Use.
 Follow the package insert carefully. Reliability of assay results cannot be guaranteed if there are any deviations from the
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instructions in this package insert.

Safety Precautions
 CAUTION: This product requires the handling of human specimens. It is recommended that all human sourced materials be

considered potentially infectious and handled in accordance with the 29 CFR 1910.1030 Occupational exposure to bloodborne
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pathogens. Biosafety Level 2 or other appropriate biosafety practices should be used for materials that contain or are suspected
of containing infectious agents.
 All samples, biological reagents and materials used in the assay should be considered potentially able to transmit infectious

agents. They should therefore be disposed in accordance with the practices of your institution. Discard all materials in a safe and
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acceptable manner and in compliance with prevailing regulatory requirements.

 This product contains Sodium Azide. Dispose of contents and containers must be in accordance with all local, regional and

national regulations.
 Refer to safety data sheets which are available on request.

Handling Precautions
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 Do not use reagent kits beyond the expiration date.

 Do not interchange reagent components from different reagents or lots.

 Prior to loading the reagent kit on the system for the first time, the reagent kit requires mixing to re-suspend magnetic

microbeads that have settled during shipment.

 For magnetic microbeads mixing instructions, refer to the Preparation of the Reagent section of this package insert.

 To avoid contamination, wear clean gloves when operating with a reagent kit and samples.
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 Over time, residual liquids may dry on the septum surface. These are typically dried salts which have no effect on assay efficacy.

 For detailed discussion of handling precautions during system operation, refer to the SNIBE service information.

STORAGE AND STABILITY

 Sealed: Stored at 2-8°C until the expiration date.
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 Opened at 2-8°C: Minimum stability is 4 weeks.

 On-board: Minimum stability is 4 weeks.
 To ensure the best kit performance, it is recommended to place opened kits in the refrigerator after the end of the intraday test
work. It is still possible to keep on using the kit beyond the opened or on-board period if the controls are found within the
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expected ranges.
 Keep upright for storage to facilitate later proper resuspension of magnetic microbeads.
 Keep away from sunlight.
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TEST PROCEDURE
Preparation of the Reagent
 Resuspension of the magnetic microbeads takes place automatically when the kit is loaded successfully, ensuring the magnetic
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microbeads are totally resuspended homogenous prior to use.

 To ensure proper test performance, strictly adhere to the operating instructions of MAGLUMI series Fully-auto

chemiluminescence immunoassay analyzer. Each test parameter is identified via a RFID CHIP on the Reagent kit. For further
information please refer to the operating instructions of MAGLUMI series Fully-auto chemiluminescence immunoassay analyzer.

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DILUTION
Sample dilution by analyzer is not available in this reagent kit.
Samples with concentrations above the measuring range can be diluted manually. After manual dilution, multiply the result by the
dilution factor. Please choose applicable diluents or ask SNIBE for advice before manual dilution.

LIMITATIONS
 The serological diagnosis of acute hepatitis A can not be only based on the IgM antibody detection using the HAV IgM assay.
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Other biological markers as well as clinical symptoms and patient history are necessary to establish such a diagnosis.
 A skillful technique and strict adherence to the instructions are necessary to obtain reliable results.
 Bacterial contamination or heat inactivation of the specimens may affect the test results.
 A result within the expected range does not rule out the presence of disease and should be interpreted together with other
diagnostic procedures.
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 Test results are reported quantitatively. However, diagnosis of a disease should not be based on the result of a single test, but
should be determined in conjunction with clinical findings in association with medical judgment.
 Any therapeutical decision should also be taken on a case-by-case basis.
 Patient samples containing human anti-mouse antibodies (HAMA) may give falsely elevated or decreased values. Although
HAMA-neutralizing agents are added, extremely high HAMA serum concentrations may occasionally influence results.
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RESULTS
Calculation of Results
The analyzer automatically calculates the HAV IgM concentration of each sample by means of a calibration curve which is
generated by a 2-point calibration master curve procedure. The results are reported in the unit of AU/mL. For further information
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please refer to the operating instructions of MAGLUMI series Fully-auto chemiluminescence immunoassay analyzer.
Interpretation of Results
The expected ranges for the HAV IgM assay were obtained by testing 190 healthy individuals and 48 patients gave the following
reference values listed below:
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 Non-reactive: A result less than 2.0 AU/mL (<2.0 AU/mL) is considered to be negative.

 Reactive: A result greater than or equal to 2.0 AU/mL (≥2.0 AU/mL) is considered to be positive.

Assay results should be interpreted in conjunction with the patient’s clinical presentation, history, and other laboratory results. All
initially reactive should be redetermined in duplicate with the HAV IgM. If the concentration values <2.0 AU/mL are found in both
cases, the samples are considered negative for antibodies. And repeatedly reactive samples should be confirmed according to
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recommended confirmatory algorithm.

PERFORMANCE CHARACTERISTICS
Precision
Precision for the HAV IgM assay was determined as described in the CLSI EP5-A2. 3 controls and 3 human serum pools
containing different concentration of analyze were assayed in duplicate at two independent runs per day for 20 testing days. The
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result is summarized in the following table:

Mean(AU/mL) Within-Run Between-Run Total
Sample
(N=80) SD(AU/mL) %CV SD(AU/mL) %CV SD(AU/mL) %CV
Negative Serum Pool 0.991 NA NA NA NA NA NA
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Low Positive Serum Pool 3.264 0.234 7.17 0.044 1.35 0.239 7.32
High Positive Serum Pool 7.765 0.170 2.19 0.333 4.29 0.374 4.82
Control 1 1.355 0.102 7.53 0.061 4.50 0.119 8.78
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Control 2 3.507 0.191 5.45 0.096 2.74 0.221 6.30

Control 3 6.020 0.248 4.12 0.184 3.06 0.313 5.20

Note: NA=Not Applicable.
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Analytical Specificity
Clinical HAV IgM negative samples, which contain potential cross-reactants including HBV, HCV, EBV, HSV, HIV, Syphilis, Toxo,
Rubella, CMV, HSV-1/2, RF, ANA, HAMA approved by commercially available CE-marked assay, were used to evaluate the
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cross-reactivity of HAV IgM assay. Of all the potential cross-reactants, none were found to cause false positive in the HAV IgM
assay. The results were summarized in the following table:

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Clinical Category Number of non-reactive Number of reactive

Anti-HBV positive 10 0
Anti-HCV positive 20 0
Anti-CMV positive 10 0
Anti-Toxo positive 10 0
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Anti-Rubella positive 10 0
Anti-EBV positive 10 0
Anti-HIV positive 10 0
Syphilis positive 10 0
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Anti-HSV positive 10 0
Anti-HSV-1/2 positive 10 0
RF positive 15 0
ANA positive 10 0
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HAMA positive 10 0
Total 145 0

Analytical Sensitivity
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The Anti-Hepatitis A Virus Mixed Titer Performance Panel PHT202 is intended for use by diagnostic manufacturers, researchers, and
clinical laboratories to develop, evaluate, or troubleshoot Anti-Hepatitis A Virus IgM test methods. Characterized samples and
comprehensive data are provided for comparative analysis.
Abbott
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Roche Siemens
AxSYM Snibe
Panel Member Elecsys * Advia Centaur*
HAVAB*
s/co s/co s/co AU/mL
PHT202-01 0.8 0.3 0.3 0.418
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PHT202-02 0.4 0.3 0.2 1.502

PHT202-03 0.5 0.3 0.2 0.190
PHT202-04 0.3 0.2 0.2 0.135
PHT202-05 2.8 8.6 >7.0 12.745
PHT202-06 1.1 2.5 4.1 10.157
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PHT202-07 1.0 2.4 4.0 11.718

PHT202-08 0.7 0.3 0.3 1.138
PHT202-09 0.4 0.2 0.2 0.209
PHT202-10 0.4 0.3 0.4 0.301
PHT202-11 3.6 15.0 >7.0 15.568
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PHT202-12 0.4 0.2 0.2 0.093

PHT202-13 0.7 0.3 0.3 0.435
PHT202-14 0.6 1.3 2.5 4.163
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PHT202-15 1.5 5.8 5.9 13.913

PHT202-16 0.4 0.4 0.4 0.595
PHT202-17 2.1 6.4 6.5 11.459
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PHT202-18 0.5 0.3 0.2 0.126

PHT202-19 1.7 3.4 3.4 11.441
PHT202-20 0.6 0.3 0.2 0.421
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PHT202-21 0.4 0.3 0.3 0.419

Note: 1. *Data from the vendor.
2. The results considered reactive are noted in bold.

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Endogenous Interference
Substances up to the following concentrations did not interfere with the assay:
 Bilirubin 100 mg/dL
 Hemoglobin 1750 mg/dL
 Triglyceride 1400 mg/dL

REFERENCES
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1. Lemon DM. Type A viral hepatitis. New developments in an old disease. New Eng J of Med 1985; 313: 1059-1067.
2. Costa-Mattioli M, Di Napoli A, Ferré V, Billaudel S, Perez-Bercoff R, Cristina J (December 2003). "Genetic variability of
hepatitis A virus". J. Gen. Virol. 84 (Pt 12): 3191–201.
3. Cristina J, Costa-Mattioli M (August 2007). "Genetic variability and molecular evolution of hepatitis A virus". Virus Res. 127
(2): 151–7.
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4. Ching KZ, Nakano T, Chapman LE, Demby A, Robertson BH (January 2002). "Genetic characterization of wild-type
genotype VII hepatitis A virus". J. Gen. Virol. 83 (Pt 1): 53–60.
5. de Paula VS, Baptista ML, Lampe E, Niel C, Gaspar AM (January 2002). "Characterization of hepatitis A virus isolates from
subgenotypes IA and IB in Rio de Janeiro, Brazil". J. Med. Virol. 66 (1): 22–7.
6. Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 541–4.
7. Matheny, SC; Kingery, JE (1 December 2012). "Hepatitis A.". Am Fam Physician. 86 (11): 1027–34; quiz 1010–2.
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8. Connor BA (2005). "Hepatitis A vaccine in the last-minute traveler". Am. J. Med. 118 (Suppl 10A): 58S–62S.
9. Stapleton JT (1995). "Host immune response to hepatitis A virus". J. Infect. Dis. 171 (Suppl 1): S9–14.
.
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Shenzhen New Industries Biomedical Engineering Co., Ltd.

No.16, Jinhui Road, Pingshan New District, Shenzhen, 518122, P.R.China.
Tel: 0086-755-21536601 Fax:0086-755-28292740
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Lotus Global Co., Ltd.

1 Four Seasons Terrace, West Drayton, Middlesex London, UB7 9GG, United Kingdom
Tel: 0044-20-75868010 Fax: 0044-20-79006187
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SYMBOLS EXPLANATIONS

Consult instructions for use Manufacturer

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Temperature limit
Use-by date
( Store at 2-8 °C)

Contains sufficient for Keep away from sunlight

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Authorized representative in the

This way up
European Community
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In vitro diagnostic medical device Kit components

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Catalogue number Batch code

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