130217020M:100 tests/kit Stability of the Reagents

130617020M:050 tests/kit Unopened at 2-8°C until the stated expiration date

130717020M:030 tests/kit Opened at 2-8°C 6 weeks
On-board 4 weeks

MAGLUMI® Anti-tissue Transglutaminase IgA (CLIA) Stability of Controls

Unopened at 2-8°C until the stated expiration date
▋INTENDED USE Opened at 10-30°C 24 hours
The kit is an in vitro chemiluminescence immunoassay for the quantitative determination of Anti-tissue Transglutaminase IgA (tTG IgA) in human serum and plasma
Opened at 2-8°C 6 weeks
using the MAGLUMI series Fully-auto chemiluminescence immunoassay analyzer and Biolumi series Integrated System, and the assay is used for an aid in the
differential diagnosis of celiac disease. Frozen at -20°C 3 months
▋SUMMARY Frozen and thawed cycles no more than 3 times
Celiac Disease is a gluten-sensitive disease that afflicts primarily the small bowel, resulting in the shortening of villi, increased numbers of intraepithelial ▋SPECIMEN COLLECTION AND PREPARATION
lymphocytes, and crypt hyperplasia1. Celiac disease is induced by the ingestion of gluten, which is derived from wheat, barley, and rye2. Celiac disease is often Specimen Types
accompanied by extraintestinal manifestations, which can be the result of aberrant immune responses but also malabsorption; These concurrent conditions can
Only the specimens listed below were tested and found acceptable.
affect various systems and organs, and include manifestations in the skin, musculoskeletal and central nervous system; Anaemia, osteoporosis, dermatitis
Specimen Types Collection Tubes
herpetiformis and gluten ataxia are among the most commonly seen characteristics; In the paediatric population, coeliac disease can lead to severe growth
disorders, such as short stature and delayed puberty due to hypogonadism3. The only effective treatment for celiac disease is complete removal of gluten from the Serum Tubes without additive/accessory, or tubes containing clot activator or clot activator with gel.
diet4. Plasma K2-EDTA or Na-heparin
The gold standard for celiac disease diagnosis is represented by the combination of mucosal changes detected by duodenal biopsy and by positivity of serological  The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of
tests including tissue transglutaminase (tTG) antibodies and deamidated gliadin peptide (DGP) antibodies5. Tissue transglutaminase or transglutaminase 2 is a all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some
calcium dependent ubiquitous enzyme consisting of 686 amino acids, which exerts several distinct physiological functions6. It is a widely expressed protein and its cases. Follow tube manufacturers’ instructions carefully when using collection tubes.
expression and enzymatic activity is increased in several diseases, including celiac disease7. Immunoglobulin A (IgA) tTG is considered the best test with Specimen Conditions
sensitivity and specificity but performs less well IgA-deficient individuals8.  Do not use grossly hemolyzed/hyperlipidaemia specimens and specimens with obvious microbial contamination.
Selective IgA deficiency is more common in patients with celiac disease than in the general population. If the levels of tTG IgA are within the normal range (or if it  Ensure that complete clot formation in serum specimens has taken place prior to centrifugation. Some serum specimens, especially those from patients receiving
is absent) and there is a high suspicion of celiac disease, a test for IgG antibodies against tissue transglutaminase should be performed2. anticoagulant or thrombolytic therapy, may exhibit increased clotting time. If the serum specimen is centrifuged before a complete clotting, the presence of fibrin
▋TEST PRINCIPLE may cause erroneous results.
Indirect chemiluminescence immunoassay.  Samples must be free of fibrin and other particulate matter.
The prediluted sample, buffer, magnetic microbeads coated with Tissue transglutaminase antigen are mixed thoroughly and incubated, performing a wash cycle after  To prevent cross contamination, use of disposable pipettes or pipette tips are recommended.
a precipitation in a magnetic field. ABEI labeled with anti-human IgA monoclonal antibody are then added and incubated, reacting to form immuno-complexes. After Preparation for Analysis
precipitation in a magnetic field, the supernatant is decanted and then a wash cycle is performed. Subsequently, the Starter 1+2 are added to initiate a  Inspect all specimens for foam. Remove foam with an applicator stick before analysis. Use a new applicator stick for each specimen to prevent cross
chemiluminescent reaction. The light signal is measured by a photomultiplier as relative light units (RLUs), which is proportional to the concentration of Anti-tissue contamination.
Transglutaminase IgA present in the sample.  Frozen specimens must be completely thawed before mixing. Mix thawed specimens thoroughly by low speed vortexing or by gently inverting. Visually inspect
▋REAGENTS the specimens. If layering or stratification is observed, mix until specimens are visibly homogeneous. If specimens are not mixed thoroughly, inconsistent results
may be obtained.
Kit Contents
 Specimens should be free of fibrin, red blood cells, or other particulate matter. Such specimens may give reliable results and must be centrifuged prior to testing.
Component Description 100 tests/kit 50 tests/kit 30 tests/kit
Transfer clarified specimen to a sample cup or secondary tube for testing. For centrifuged specimens with a lipid layer, transfer only the clarified specimen and not
Lyophilized Magnetic Magnetic microbeads coated with Tissue transglutaminase antigen (~2.00 the lipemic material.
1 bottle 1 bottle 1 bottle
Microbeads μg/bottle) in PBS buffer, NaN3 (<0.1%).  The sample volume required for a single determination of this assay is 10 µL.
Magnetic Microbeads Buffer PBS buffer, NaN3 (<0.1%). 2.8 mL 2.8 mL 2.8 mL Specimen Storage
Calibrator Low A low concentration of tTG IgA in PBS buffer, NaN3 (<0.1%). 1.0 mL 1.0 mL 1.0 mL Specimens removed from the separator, red blood cells or clot may be stored up to 6 hours at 10-30°C or 7 days at 2-8°C, or 6 months frozen at -20°C. Frozen
Calibrator High A high concentration of tTG IgA in PBS buffer, NaN3 (<0.1%). 1.0 mL 1.0 mL 1.0 mL specimens subjected to up to 1 freeze/thaw cycle have been evaluated.
Buffer BSA, NaN3 (<0.1%). 17.5 mL 9.5 mL 6.3 mL Specimen Shipping
ABEI labeled with anti-human IgA monoclonal antibody (~50.0 ng/mL) in  Package and label specimens in compliance with applicable local regulations covering the transport of clinical specimens and infectious substances.
ABEI Label 22.5 mL 12.0 mL 7.8 mL  Do not exceed the storage limitations listed above.
Tris-HCl buffer, NaN3 (<0.1%).
Diluent PBS buffer, NaN3 (<0.1%). 25.0 mL 13.5 mL 8.0 mL Specimen Dilution
Control 1 A low concentration of tTG IgA (10.0 AU/mL) in PBS buffer, NaN3 (<0.1%). 1.0 mL 1.0 mL 1.0 mL  Samples, with tTG IgA concentrations above the analytical measuring interval, can be diluted with Diluent either by following automated dilution protocol or
Control 2 A high concentration of tTG IgA (100 AU/mL) in PBS buffer, NaN3 (<0.1%). 1.0 mL 1.0 mL 1.0 mL manual dilution procedure. The recommended dilution ratio is 1:20. The concentration of the diluted sample must be >20 AU/mL.
 For manual dilution, multiply the result by the dilution factor. For dilution by the analyzers, the analyzer software automatically takes the dilution into account when
Magnetic Microbeads is lyophilized and must be reconstituted with Magnetic Microbeads Buffer, refer to the Preparation of Magnetic Microbeads
calculating the sample concentration.
section.
▋PROCEDURE
Warnings and Precautions
Materials Provided
 For in vitro diagnostic use.
Anti-tissue Transglutaminase IgA (CLIA) assay, control barcode labels.
 For professional use only.
Materials Required (But Not Provided)
 Exercise the normal precautions required for handling all laboratory reagents.
 Personal protective measures should be taken to prevent any part of the human body from contacting samples, reagents, and controls, and should comply with  General laboratory equipment.
local operating requirements for the assay.  Fully-auto chemiluminescence immunoassay analyzer Maglumi 600, Maglumi 800, Maglumi 1000, Maglumi 2000, Maglumi 2000 Plus, Maglumi 4000, Maglumi
 A skillful technique and strict adherence to the package insert are necessary to obtain reliable results. 4000 Plus, MAGLUMI X3, MAGLUMI X6,MAGLUMI X8, or Integrated System Biolumi 8000 and Biolumi CX8.
 Do not use kit beyond the expiration date indicated on the label.  Additional accessories of test required for the above analyzers include Reaction Module, Starter 1+2, Wash Concentrate, Light Check, Tip, and Reaction Cup.
 Do not interchange reagent components from different reagents or lots. Specific accessories and accessories’ specification for each model refer to corresponding Analyzer Operating Instructions.
 Avoid foam formation in all reagents and sample types (specimens, calibrators and controls).  Please use accessories specified by Snibe to ensure the reliability of the test results.
 All waste associated with biological samples, biological reagents and disposable materials used for the assay should be considered potentially infectious and Assay Procedure
should be disposed of in accordance with local guidelines. Preparation of the Reagent
 This product contains sodium azide. Sodium azide may react with lead or copper plumbing to form highly explosive metal azides. Immediately after disposal, flush  Take the reagent kit out of the box and visually inspect the integral vials for leaking at the sealing film or elsewhere. If there is no leakage, please tear off the sealing film
with a large volume of water to prevent azide build-up. For additional information, see Safety Data Sheets available for professional user on request. carefully.
Note: If any serious incident has occurred in relation to the device, please report to Shenzhen New Industries Biomedical Engineering Co., Ltd. (Snibe) or our Preparation of Magnetic Microbeads
 The Magnetic Microbeads is provided in a lyophilized form. The vial containing the lyophilized magnetic microbeads must be opened carefully and
authorized representative and the competent authority of the Member State in which you are established.
reconstituted with the Magnetic Microbeads Buffer.
Reagent Handling
 Remove 2 mL Magnetic Microbeads Buffer from the magnetic microbeads tube (blue collar and serrated reagent tube on the bottom) into the vial
 To avoid contamination, wear clean gloves when operating with a reagent kit and sample. When handling reagent kit, replace the gloves that have been in contact containing lyophilized magnetic microbeads before use, cover with a rubber stopper, and gently shake. Allow the dissolved magnetic microbeads
with samples, since introduction of samples will result in unreliable results. to stand for 10-15 minutes.
 Do not use kit in malfunction conditions; e.g., the kit leaking at the sealing film or elsewhere, obviously turbid or precipitation is found in reagents (except for  Swirl gently to ensure homogeneity. Avoid heavy shaking when dissolving (avoid formation of foam).
Magnetic Microbeads) or control value is out of the specified range repeatedly. When kit in malfunction conditions, please contact Snibe or our authorized  Transfer all reconstituted magnetic microbeads in vial to the magnetic microbeads tube and mix it with the remaining Magnetic Microbeads Buffer
distributor. evenly, then place prepared kit onto the analyzer.
 To avoid evaporation of the liquid in the opened reagent kits in refrigerator, it is recommended that the opened reagent kits to be sealed with reagent seals  After use, the kit including the reconstituted magnetic microbeads should be stored at 2-8°C in an upright position.
contained within the packaging. The reagent seals are single use, and if more seals are needed, please contact Snibe or our authorized distributor.  Open the reagent area door; hold the reagent handle to get the RFID label close to the RFID reader (for about 2s); the buzzer will beep; one beep sound indicates
 Over time, residual liquids may dry on the septum surface. These are typically dried salts and have no effect on assay efficacy. successful sensing.
 Use always the same analyzer for an opened reagent integral.  Keeping the reagent straight insert to the bottom along the blank reagent track.
 For magnetic microbeads mixing instructions, refer to the Preparation of the Reagent section of this package insert.  Observe whether the reagent information is displayed successfully in the software interface, otherwise repeat the above two steps.
 For further information about the reagent handing during system operation, please refer to Analyzer Operating Instructions.  Resuspension of the magnetic microbeads takes place automatically when the kit is loaded successfully, ensuring the magnetic microbeads are totally resuspended
Storage and Stability homogenous prior to use.
 Do not freeze the integral reagents. Assay Calibration
 Store the reagent kit upright to ensure complete availability of the magnetic microbeads.  Select the assay to be calibrated and execute calibration operation in reagent area interface. For specific information on ordering calibrations, refer to the calibration
 Protect from direct sunlight. section of Analyzer Operating Instructions.
 Execute recalibration according to the calibration interval required in this package insert.

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Quality Control interferents in a protocol (EP7-A2) of the CLSI. The measurement deviation of the interference substance is within ±10%. The following results were obtained:
 When new lot used, check or edit the quality control information. Interference No interference up to Interference No interference up to
 Scan the control barcode, choose corresponding quality control information and execute testing. For specific information on ordering quality controls, refer to the Bilirubin 90 mg/dL Rheumatoid factor 2500 IU/mL
quality control section of the Analyzer Operating Instructions. Hemoglobin 1000 mg/dL ANA 398 AU/mL
Sample Testing
Intralipid 3000 mg/dL HAMA 40 ng/mL
 After successfully loading the sample, select the sample in interface and edit the assay for the sample to be tested and execute testing. For specific information on
K2-EDTA 22.75 μmol/mL Heparin sodium salt 80 IU/mL
ordering patient specimens, refer to the sample ordering section of the Analyzer Operating Instructions.
To ensure proper test performance, strictly adhere to Analyzer Operating Instructions. High-Dose Hook
Calibration No high-dose hook effect was seen for tTG IgA concentrations up to 8000 AU/mL.
Traceability: This method has been standardized against the Snibe internal reference standard. Method Comparison
Test of assay specific calibrators allows the detected relative light unit (RLU) values to adjust the master curve. A comparison of the tTG IgA assay with a commercially available immunoassay, gave the following correlations (AU/mL):
Recalibration is recommended as follows: Number of samples measured: 120
 Whenever a new lot of Reagent or Starter 1+2 is used. Passing-Bablok: y=1.0101x-0.0582, τ=0.966.
 Every 7 days. The clinical specimen concentrations were between 2.030 and 364.156 AU/mL.
 The analyzer has been serviced. ▋REFERENCES
 Control values lie outside the specified range. 1. Marietta E V, Rashtak S, Murray J A. Correlation analysis of celiac sprue tissue transglutaminase and deamidated gliadin IgG/IgA[J]. World Journal of
 Each time a new kit is used. Gastroenterology: WJG, 2009, 15(7): 845.
Quality Control 2. Green P H R, Cellier C. Celiac disease[J]. New England Journal of Medicine, 2007, 357(17): 1731-1743.
Controls are recommended for the determination of quality control requirements for this assay and should be run in singlicate to monitor the assay performance. 3. Leffler D A , Green P, Fasano A . Extraintestinal manifestations of coeliac disease[J]. Nature Reviews Gastroenterology & Hepatology, 2015.
Refer to published guidelines for general quality control recommendations, for example Clinical and Laboratory Standards Institute (CLSI) Guideline C24 or other 4. Bai J C, Ciacci C. World gastroenterology organisation global guidelines: Celiac disease February 2017[J]. Journal of clinical gastroenterology, 2017, 51(9):
published guidelines9. 755-768.
Quality control is recommended once per day of use, or in accordance with local regulations or accreditation requirements and your laboratory’s quality control 5. Caio G, Volta U, Sapone A, et al. Celiac disease: a comprehensive current review[J]. BMC Medicine, 2019, 17(1): 1-20.
procedures, quality control could be performed by running the Anti-tissue Transglutaminase IgA assay: 6. Di Sabatino A, Vanoli A, Giuffrida P, et al. The function of tissue transglutaminase in celiac disease[J]. Autoimmunity reviews, 2012, 11(10): 746-753.
 Whenever the kit is calibrated. 7. Katt W P , Antonyak M A , Cerione R A . The diamond anniversary of tissue transglutaminase: a protein of many talents[J]. Drug Discovery Today,
 Whenever a new lot of Starter 1+2 or Wash Concentrate is used. 2018:575-591.
Controls are only applicable with MAGLUMI and Biolumi systems and only used matching with the same top seven LOT numbers of corresponding reagents. For 8. Olen O , AH Gudjónsdóttir, Browaldh L , et al. Antibodies against deamidated gliadin peptides and tissue transglutaminase for diagnosis of pediatric celiac
each target value and range refer to the label. disease.[J]. Journal of Pediatric Gastroenterology and Nutrition, 2012, 55(6):695-700.
The performance of other controls should be evaluated for compatibility with this assay before they are used. Appropriate value ranges should be established for all 9. CLSI. Statistical Quality Control for Quantitative Measurement Procedures: Principles and Definitions. 4th ed. CLSI guideline C24. Wayne, PA: Clinical and
quality control materials used. Laboratory Standards Institute; 2016.
Control values must lie within the specified range, whenever one of the controls lies outside the specified range, calibration should be repeated and controls 10. Robert W. Schroff, Kenneth A. Foon, Shannon M. Beatty, et al. Human Anti-Murine Immunoglobulin Responses in Patients Receiving Monoclonal Antibody
retested. If control values lie repeatedly outside the predefined ranges after successful calibration, patient results must not be reported and take the following Therapy[J]. Cancer Research, 1985, 45(2):879-885.
actions: 11. Primus F J, Kelley E A, Hansen H J, et al. "Sandwich"-type immunoassay of carcinoembryonic antigen in patients receiving murine monoclonal antibodies for
 Verify that the materials are not expired. diagnosis and therapy[J]. Clinical Chemistry, 1988, 34(2):261-264.
 Verify that required maintenance was performed. 12. Boscato L M , Stuart M C . Heterophilic antibodies: a problem for all immunoassays[J]. Clin Chem 1988;34(1):27-33.
 Verify that the assay was performed according to the package insert. ▋SYMBOLS EXPLANATIONS
 If necessary, contact Snibe or our authorized distributors for assistance.
If the controls in kit are not enough for use, please order Anti-tissue Transglutaminase IgA (CLIA) Controls (REF: 160201443MT) from Snibe or our authorized Consult instructions for use Manufacturer
distributors for more.
▋RESULTS
Calculation Temperature limit
The analyzer automatically calculates the tTG IgA concentration in each sample by means of a calibration curve which is generated by a 2-point calibration master Use-by date
(Store at 2-8°C)
curve procedure. The results are expressed in AU/mL. For further information please refer to the Analyzer Operating Instructions.
Interpretation of Results
The expected range for the tTG IgA assay was obtained by testing 126 tTG IgA positive patients and 130 tTG IgA negative people in China, gave the following
Contains sufficient for<n> tests Keep away from sunlight
expected value by ROC curve:
 Non-reactive: A result less than 20.0 AU/mL (<20.0 AU/mL) is considered to be negative.
 Reactive: A result greater than or equal to 20.0 AU/mL (≥20.0 AU/mL) is considered to be positive.
Authorized representative in the European
Results may differ between laboratories due to variations in population and test method. It is recommended that each laboratory establish its own reference interval. This way up
▋LIMITATIONS Community
 Results should be used in conjunction with patient’s medical history, clinical examination and other findings.
 If the tTG IgA results are inconsistent with clinical evidence, additional testing is needed to confirm the result.
 Specimens from patients who have received preparations of mouse monoclonal antibodies for diagnosis or therapy may contain human anti-mouse antibodies In vitro diagnostic medical device Kit component
(HAMA). Such specimens may show either falsely elevated or depressed values when tested with assay kits which employ mouse monoclonal antibodies10,11.
Additional information may be required for diagnosis.
 Heterophilic antibodies in human serum can react with reagent immunoglobulins, interfering with in vitro immunoassays. Patients routinely exposed to animals or
Catalogue number Batch code
animal serum products can be prone to this interference and anomalous values may be observed12.
 Bacterial contamination of the specimens may affect the test results.
▋SPECIFIC PERFORMANCE CHARACTERISTICS
Representative performance data are provided in this section. Results obtained in individual laboratories may vary. CE marking Reconstitute with
Precision
Precision was determined using the assay, samples and controls in a protocol (EP05-A3) of the CLSI (Clinical and Laboratory Standards Institute): duplicates at two
independent runs per day for 5 days at three different sites using three lots of reagent kits (n = 180). The following results were obtained:
MAGLUMI® and Biolumi® are trademarks of Snibe. All other product names and trademarks are the property of their respective owners.
Mean (AU/mL) Within-Run Between-Run Reproducibility
Sample
(n=180) SD (AU/mL) %CV SD (AU/mL) %CV SD (AU/mL) %CV
Shenzhen New Industries Biomedical Engineering Co., Ltd.
Serum Pool 1 5.328 0.168 3.15 0.109 2.05 0.272 5.11 No.23, Jinxiu East Road, Pingshan District, 518122 Shenzhen, P.R. China
Serum Pool 2 21.217 0.824 3.88 0.308 1.45 1.138 5.36 Tel: +86-755-21536601 Fax:+86-755-28292740
Serum Pool 3 202.515 5.879 2.90 4.488 2.22 10.634 5.25
Plasma Pool 1 5.419 0.183 3.38 0.110 2.03 0.281 5.19 Shanghai International Holding Corp. GmbH (Europe)
Plasma Pool 2 20.917 0.676 3.23 0.351 1.68 0.944 4.51 Eiffestrasse 80, 20537 Hamburg, Germany
Plasma Pool 3 201.160 5.206 2.59 3.646 1.81 8.549 4.25 Tel: +49-40-2513175 Fax: +49-40-255726
Control 1 10.045 0.326 3.25 0.148 1.47 0.481 4.79
Control 2 98.304 3.325 3.38 0.765 0.78 5.852 5.95
Linear Range
2.00-400 AU/mL (defined by the Limit of Quantitation and the maximum of the master curve).
Reportable Interval
1.00-8000 AU/mL (defined by the Limit of Detection and the maximum of the master curve×Recommended Dilution Ratio).
Analytical Sensitivity
Limit of Blank (LoB) =0.500 AU/mL.
Limit of Detection (LoD) =1.00 AU/mL.
Limit of Quantitation (LoQ) =2.00 AU/mL.
Analytical Specificity
Interference
Interference was determined using the assay, three samples containing different concentrations of analyte were spiked with potential endogenous and exogenous

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