BIOMÉRIEUX

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VIDAS® TB-IGRA (TBRA)

INTENDED USE
The VIDAS® TB-IGRA (TBRA) assay is intended as an aid in the diagnosis of individuals infected with Mycobacterium
tuberculosis (latent infection or active disease).
Using human heparinized whole blood, an automated in vitro stimulation with M. tuberculosis associated peptide
antigens is performed on the VIDAS® 3 instrument. When stimulated in this manner, M. tuberculosis specific immune
T cells can produce IFN‑γ (Interferon Gamma). Although the VIDAS® TB‑IGRA assay quantitatively detects the IFN‑γ, the
interpretation of the result for a single patient is strictly qualitative.
The VIDAS® TB‑IGRA (TBRA) assay is an indirect test for M. tuberculosis infection (including disease) and is intended
for use in conjunction with risk assessment, radiography, and other medical and diagnostic evaluations.
SUMMARY AND EXPLANATION
It is estimated that one quarter of worldwide population is infected by Mycobacterium tuberculosis.1
Upon initial infection with Mycobacterium tuberculosis (Mtb), a state of dormancy normally occurs, known as latent
tuberculosis infection (LTBI).2 In some patients LTBI may progress to active disease (TB), and it is only in this latter state
that TB can be highly infectious and associated with morbidity and mortality.2
The sole available method for diagnosis of TB infection was, for more than 100 years, the tuberculin skin test (TST). This
involves intradermal injection of Mtb antigens and subsequent observation (at 48–72 hours) for the induction of
cutaneous induration, resulting from a delayed-type hypersensitivity response to the antigens.3 However, the TST has
sub-optimal specificity for detecting Mtb infection due to a stimulation solution containing antigens which are also present
in other mycobacteria (e.g. are cross-reactive), resulting in false-positive results in individuals with either prior
immunization with the Bacillus Calmette Guérin (BCG) vaccine or non-tuberculous mycobacteria.4
Interferon‑Gamma Release Assays (IGRA) have been developed as an alternative immunodiagnostic approach to TST
for detecting M. tuberculosis infection. The presence of Mtb‑specific peripheral T cells can be advantageously used for
indirect testing for prior Mtb infection using a simple blood sample. After incubation with a cocktail of Mtb synthetic
peptides, Mtb‑specific T cells can recognize these antigens and react as if they were in the presence of actual Mtb
organisms, notably by producing IFN‑γ, a key driver in the Mtb‑specific cellular immune defenses.5,6
Therefore, detecting production of IFN‑γ after the stimulation step can provide useful information regarding the potential
presence of Mtb‑specific immune defenses due to prior contact with Mtb.
Interferon‑gamma release assays render a positive result for both latent and active forms of infection. The active disease
form of infection is identifiable with additional clinical information such as historical, physical, radiological and
bacteriological data. Groups at risk for latent TB infection are well defined: people at high risk of LTBI without an
increased risk of progression to active TB, people at higher risk of progression to active TB. IFN‑γ assays can be used as
a tool to screen such populations.7

It should be noted that medical treatments or conditions that impair immune system responses may impact test results.8
PRINCIPLE
Caution:
The VIDAS® TB-IGRA assay is a fully automated assay using whole blood. Sample preparation and instructions for use
vary from usual VIDAS® assays. Please pay particular attention to the following:
• Sections of the package insert: Samples, Types of tubes validated, Sample Transport, Sample stability.
• Specified order for opening and closing the stimulation reagent vials: NIL (Negative Control), then AG (Antigen),
then MIT (Mitogen = Positive Control). Open the first vial, add water, close the vial, and move on to the next vial, in
the pre-mentioned order.

• Use non-contaminated distilled water or sterile distilled water or deionized water or sterile deionized water to
avoid any risk of contamination, as contaminated water can have an impact on the results of the test.
• Three reagent strips are required for each patient sample test.

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Stimulation steps:
Blood and stimulation reagent distribution: The patient sample and provided stimulation reagents NIL (Negative Control),
AG (Antigen), and MIT (Mitogen = Positive Control) are distributed by the automated pipetting unit of the VIDAS® 3
instrument in 3 different strips.
Incubation: Once the distribution has been executed, a 16‑hour incubation at +37°C in the VIDAS® 3 follows. Once the
incubation is finished, the stimulated sample (supernatant) is used for the ELFA (Enzyme Linked Fluorescent Assay) part
of the TB‑IGRA assay.
Assay steps:
The assay principle combines a two-step sandwich enzyme immunoassay method with a final fluorescence detection
(ELFA).
The single-use Solid Phase Receptacle (SPR) serves as the solid phase as well as the pipetting device. Reagents for the
assay are ready-to-use and pre-dispensed in the sealed single-use reagent strips. All of the assay steps are performed
automatically by the instrument.
The stimulated sample is collected, and then diluted in a suitable diluent. The mixture is cycled in and out of the SPR
device several times. This operation enables IFN‑γ to bind with the capture antibodies fixed to the interior wall of the SPR
device.
The conjugate is cycled in and out of the SPR device several times. This operation enables the conjugate to bind with the
immune complexes that are fixed to the interior wall of the SPR device, and to form a sandwich. Unbound components
are eliminated during washing steps.
During the final detection step, the substrate (4-Methylumbelliferyl phosphate) is cycled in and out of the SPR device.
The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone), the
fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the concentration of
IFN‑γ in the stimulated sample.
At the end of the assay, the results are automatically calculated by the instrument according to the calibration curve
stored in memory.
CONTENT OF THE KIT (60 TESTS)*- RECONSTITUTION OF REAGENTS
*Caution: 1 patient test requires 3 strips and 3 SPR devices.

60 Strips(a) (TBRA) STR Ready-to-use.

60 SPR devices (TBRA) SPR Ready-to-use.
2 x 30 Interior of SPR device coated with anti-IFN‑γ antibodies.
S1 Calibrator(b) (TBRA) S1 Reconstitute with 2 mL of distilled or sterile distilled or deionized or sterile
1 x 2 g before deionized water. Add water slowly and progressively because this
reconstitution lyophilized reagent is volatile.
(lyophilized) Leave for 5 to 10 minutes at +18°C/+25°C. Mix by inverting several times and
then using a vortex-type mixer until completely dissolved. Use a vortex-type mixer
at low speed to limit foam formation.
After reconstitution, the calibrator is stable for 3 months at +2°C/+8°C, or until the
expiration date of the kit when stored at -31°C/-19°C.
Three freeze/thaw cycles are possible. After thawing, mix the calibrator using a
vortex-type mixer prior to use on the instrument.
Buffer containing recombinant IFN‑γ + stabilizer of animal origin + preservative.
MLE (Master Lot Entry) data indicate the calibrator concentration in IU/mL
("Calibrator (S1) Dose Value") and the acceptable range in "Relative
Fluorescence Value" (Calibrator (S1) RFV Range).

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C1 Positive control(b) C1 Reconstitute with 2 mL of distilled or sterile distilled or deionized or sterile

(TBRA) deionized water. Add water slowly and progressively because this
1 x 2 g before lyophilized reagent is volatile.
reconstitution Leave for 5 to 10 minutes at +18°C/+25°C. Mix by inverting several times and
(lyophilized) then using a vortex-type mixer until completely dissolved. Use a vortex-type mixer
at low speed to limit foam formation.
After reconstitution, the control is stable for 3 months at +2°C/+8°C, or until the
expiration date of the kit when stored at -31°C/-19°C.
Three freeze/thaw cycles are possible. After thawing, mix the control using a
vortex-type mixer prior to use on the instrument.
Buffer containing recombinant IFN‑γ + stabilizer of animal origin + preservative.
MLE data indicate the acceptable range in IU/mL ("Control C1 (+) Dose Value
Range").
Stimulation reagent NIL NIL Using a new tip or a single-use pipette, reconstitute with 5 mL of distilled or
(TBRA) sterile distilled or deionized or sterile deionized water. Add water slowly and
White cap progressively because this lyophilized reagent is volatile.

2 x 3 g before Leave for 5 to 10 minutes at +18°C/+25°C. Mix by inverting several times and
reconstitution then using a vortex-type mixer until completely dissolved.

(lyophilized)
Note: Volatile substance.
Handle with care to
ensure that reagent
reconstitution is correct.
Stimulation reagent AG AG
(TBRA)
Green cap
After reconstitution, the stimulation reagent is stable for 3 months at +2°C/+8°C,
or until the expiration date of the kit when stored at -31°C/-19°C.
Nine freeze/thaw cycles are possible. After thawing, mix the stimulation reagent
using a vortex-type mixer prior to use on the instrument.
Buffer containing recombinant proteins.
This stimulation reagent acts as a negative control for the stimulation step,
enabling the measurement of the basal level of IFN‑γ in the patient’s samples
before stimulation.
Using a new tip or a single-use pipette, reconstitute with 5 mL of distilled or
sterile distilled or deionized or sterile deionized water. Add water slowly and
progressively because this lyophilized reagent is volatile.

2 x 3 g before Leave for 5 to 10 minutes at +18°C/+25°C. Mix by inverting several times and
reconstitution then using a vortex-type mixer until completely dissolved.

(lyophilized)
Note: Volatile substance.
Handle with care to
ensure that reagent
reconstitution is correct.
After reconstitution, the stimulation reagent is stable for 3 months at +2°C/+8°C,
or until the expiration date of the kit when stored at -31°C/-19°C.
Nine freeze/thaw cycles are possible. After thawing, mix the stimulation reagent
using a vortex-type mixer prior to use on the instrument.
Buffer containing recombinant proteins and peptides.
Stimulation reagent containing Mycobacterium tuberculosis peptides. The
peptides contained in this reagent trigger a T‑cell stimulation, showing evidence of
a previous encounter with M. tuberculosis.

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Stimulation reagent MIT MIT Using a new tip or a single-use pipette, reconstitute with 5 mL of distilled or
(TBRA) sterile distilled or deionized or sterile deionized water. Add water slowly and
Red cap progressively because this lyophilized reagent is volatile.

2 x 3 g before Leave for 5 to 10 minutes at +18°C/+25°C. Mix by inverting several times and
reconstitution then using a vortex-type mixer until completely dissolved.

(lyophilized) After reconstitution, the stimulation reagent is stable for 3 months at +2°C/+8°C,
or until the expiration date of the kit when stored at -31°C/-19°C.
Note: Volatile substance.
Handle with care to Nine freeze/thaw cycles are possible. After thawing, mix the stimulation reagent
ensure that reagent using a vortex-type mixer prior to use on the instrument.
reconstitution is correct. Buffer containing lectin extracted from plants.
Stimulation reagent acting as a positive control for the stimulation step. The lectin
molecule contained in this reagent triggers a non‑specific stimulation of T cells.
The detection of IFN‑γ validates the patient’s test.
Specifications for the factory master data required to calibrate the assay: MLE barcode printed on the box label.
1 package insert downloadable from www.biomerieux.com/techlib

(a)
DANGER WARNING EUH208 / H317 / H318 / H319 / P261 / P280 / P302 + P352 / P305 +
P351 + P338

(b) WARNING EUH208 / H317 / P261 / P280 / P302 + P352

Hazard statements
• EUH208: Contains 2-methyl-2H-isothiazolin-3-one. May produce an allergic reaction.
• H317: May cause an allergic skin reaction.
• H318: Causes serious eye damage.
• H319: Causes serious eye irritation.

Precautionary statements
• P261: Avoid breathing dust/fume/gas/mist/vapours/spray.
• P280: Wear protective gloves/protective clothing/eye protection/face protection.
• P302 + P352: IF ON SKIN: Wash with plenty of soap and water.
• P305 + P351 + P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if
present and easy to do. Continue rinsing.

For further information, consult the Safety Data Sheet.

The SPR device

The interior of the SPR device is coated with anti‑IFN‑γ antibodies. Each SPR device is identified by the "TBRA" code.
Only remove the required number of SPR devices from the pouch and carefully reseal the pouch after opening.

The Reagent Strip

The strip consists of 10 wells covered with a labeled foil seal. The label comprises a barcode which mainly indicates the
assay code, kit lot number, and expiration date.
The calibrator and control can be manually or automatically introduced in the first well of the strip. The patient sample is
automatically transferred and incubated with the stimulation reagents in the third well of the reagent strip.
The last well of each strip is a cuvette in which the fluorometric reading is performed. The wells in the center section of
the strip contain the various reagents required for the assay.

Description of the TBRA strip

The strip contains diethanolamine and sodium azide. Refer to the hazard statements “H” and precautionary statements
“P” indicated above.(a)

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Well Reagents
1 Sample well for calibration protocol only.
2-3-4 Empty wells (foiled).
5 Sample diluent: buffer + protein stabilizer of animal origin + preservative + mouse IgG.
6 Conjugate: buffer containing anti‑IFN‑γ antibodies + stabilizer of animal origin +
preservative.
7-8-9 Wash buffers: buffer + preservative.
10 Reading cuvette with substrate: 4-Methylumbelliferyl phosphate (0.6 mmol/L) +
preservative.

MATERIALS AND DISPOSABLES REQUIRED BUT NOT PROVIDED

• Single-use pipette and/or micropipettes to dispense the appropriate volumes.
• General laboratory equipment.
• Non-contaminated distilled water or sterile distilled water or deionized water or sterile deionized water.
• Powderless disposable gloves.
• 4 mL vacuum blood-collection plastic tubes with lithium heparin (13 mm x 75 mm).
• Instrument of the VIDAS® family: VIDAS® 3, with software version 1.4 minimum or higher.
• For other specific materials and disposables, please refer to the Instrument User Manual.

WARNINGS AND PRECAUTIONS

• For in vitro diagnostic use only.
• For professional use only, by qualified laboratory personnel in clinical laboratories.
• This kit does not contain products of human origin.
• This kit contains products of animal origin. Certified knowledge of the origin and/or sanitary state of the animals does
not totally guarantee the absence of transmissible pathogenic agents. It is therefore recommended that these
products be treated as potentially infectious, and handled observing the usual safety precautions (do not ingest; do
not inhale).
• Use non-contaminated distilled water or sterile distilled water or deionized water or sterile deionized water to avoid
any risk of contamination, as contaminated water can have an impact on the results of the test.
• Do not use the SPR devices if the pouch is pierced or if the dot sealing a SPR device has come unstuck.
• Do not use visibly deteriorated strips (damaged foil or plastic). In case of system failure during a run and if the
system allows the reuse of strips and SPR devices, strips only pierced in well 3 can still be used with the associated
SPR devices, without having to replace them.
Please refer to the table below for conditions of reuse:
Use-by period for reuse of pierced strips and SPR
devices after system error
If reagents are used for calibration/ Internal Quality Stored at +2°C/+8°C until expiration of the kit
Control
If reagents are used for a patient test Stored at +2°C/+8°C up to 24 hours
• Do not use reagents after the expiration date indicated on the box label.
• Do not mix reagents (or disposables) from different lots.
• Do not pool the stimulation reagent vials.
• Do not use aliquot cups to load stimulation reagents into the VIDAS® 3 instrument.
• VIDAS® TB-IGRA assay reagents are only for use with the VIDAS® 3 instrument.
• Use powderless gloves, as powder has been reported to cause false results for certain enzyme immunoassay tests.
• Kit reagents contain sodium azide which can react with lead or copper plumbing to form explosive metal azides. If
any liquid containing sodium azide is disposed of in the plumbing system, drains should be flushed with water to
avoid build-up.
• Refer to the hazard statements “H” and precautionary statements “P” indicated above.
• Spills should be wiped up thoroughly after treatment with liquid detergent or a solution of household bleach
containing at least 0.5% sodium hypochlorite. See the User Manual for cleaning spills on or in the instrument. Do not
autoclave solutions containing bleach.
• The instrument should be regularly cleaned and decontaminated (refer to the User Manual for user and preventive
maintenance operations).

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STORAGE CONDITIONS
• Store the kit at +2°C/+8°C. Store all unused reagents at +2°C/+8°C.
• Only calibrators, controls, and stimulation reagents can be frozen after reconstitution.
• After opening the kit, check that the SPR pouches are correctly sealed and undamaged. If not, do not use the SPR
devices.
• After use, carefully reseal the pouch with the desiccant inside to maintain stability of the SPR devices, and
return the complete kit to +2°C/+8°C.
• If stored according to the recommended conditions, all components are stable until the expiration date indicated on
the box label. Refer to the kit composition table for special storage conditions.

SAMPLES
Types of tubes validated
• 4 mL vacuum blood-collection plastic tubes with lithium heparin (13 mm x 75 mm) only.

Note:
• Do not use a syringe for blood draw.
• Do not use tubes with separator gel or beads for whole blood testing.
• Do not use aliquot tube for whole blood testing.
• Blood sampling tubes may vary from one manufacturer to another depending on the materials and additives used. It
is the responsibility of each laboratory to validate the sample tube used and to follow the manufacturer’s
recommendations for use.

Sample type and collection

4 mL human whole blood in lithium heparin tube.
Sample Transport
It is recommended to transport the blood sample tubes in an upright, vertical position to avoid any risk of system error.
The blood sample tubes should be transported at a temperature compliant with the workflows detailed below.
Sample preparation and stability
The current WHO/DIL/LAB/99.1 document provides recommendations for sample preparation. 9
For use of sample tubes, refer to the tube manufacturer’s recommendations for use.
The pre-analytical step, including the preparation of blood samples, is an essential first step when performing medical
analyses. In accordance with Good Laboratory Practice, this step is performed under the responsibility of the laboratory
manager.
It is recommended to store the blood sample tubes in an upright, vertical position to avoid any risk of system error.
Two workflows are possible when performing a VIDAS® TB-IGRA assay:

or

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Note: in the second workflow, it is possible to either store the sample at +2°C/+8°C directly or keep the sample at
+18°C/+25°C up to 1h30 prior storage at +2°C/+8°C. Remove from storage at +2°C/+8°C for at least 30 minutes prior to
use on the instrument.
Important:
• Do not freeze samples.
• Do not centrifuge samples.
• Do not dilute samples.
• Do not mix samples using a vortex-type mixer.
• Do not incubate samples.

Sample-related interference
It is recommended not to use hemolyzed, lipemic, icteric samples, and, if possible, to collect a new sample.
Refer to the section PERFORMANCE – Study of drugs and other potentially interfering substances for the
compounds tested.
INSTRUCTIONS FOR USE
For complete instructions, see the Instrument User Manual.
Reading MLE data
When opening a new lot of reagents
With the external instrument barcode reader, scan the MLE data on the box label before performing the test.
Note: The master lot data need only be entered once for each lot.
Calibration
Calibration, using the calibrator provided in the kit, must be performed each time a new lot of reagents is opened, after
the MLE data have been entered, and then every 56 days. This operation provides instrument-specific calibration curves
and compensates for possible minor variations in assay signal throughout the shelf life of the kit.
The calibrator, identified by S1, must be tested in duplicate.
The calibrator value must be within the set RFV (Relative Fluorescence Value) range. If this is not the case, recalibrate.
Kit control
One control is included in this kit. The kit control must be performed immediately after opening a new kit to ensure that
reagent performance has not been altered. The control, identified by C1, must be tested singly.
Each calibration must also be checked using this control.
The instrument will only be able to check the control value if it is identified by C1. Results cannot be validated if the
control value deviates from the expected values.
Note: Any other use of the kit control is under the customer’s responsibility.
Procedure

Launching a calibration or a C1 control:

1. Remove the kit from storage at +2°C/+8°C and take out the required reagents. Carefully reseal the SPR pouch
and return the kit to +2°C/+8°C. The reagents can be used immediately.
2. Insert the "TBRA" SPR devices and "TBRA" strips into the instrument. Check to make sure the color labels with the
assay code on the SPR devices and the Reagent Strips match.
3. The calibrator must be identified by "S1" and tested in duplicate. The control identified by "C1" must be tested singly.
4. Mix the calibrator and control using a vortex-type mixer. Open the vials gently to avoid projections.
5. Ensure that the calibrator and control are free of bubbles.
6. For this test, the calibrator and control test portion is 150 µL.
7. Initiate the assay as directed in the User Manual. The assay will be completed within approximately 43 minutes for
the calibrator and control.
8. Close the vials and return them to the required temperature after pipetting.
9. After the assay is completed, remove the Solid Phase Receptacles (SPR) and strips from the instrument.
10. Dispose of the used Solid Phase Receptacles (SPR) and strips into an appropriate recipient.

Launching a sample analysis:

For optimal results, refer to all the paragraphs in the SAMPLES section.
All of the sample analysis steps are performed automatically by the instrument.

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If the patient's sample tube is stored at +18°C/+25°C, then the test can be launched immediately. If the patient's sample
tube was stored at +2°C/+8°C, equilibrate at +18°C/+25°C between 30 minutes and 1h30 before use.
1. Remove the kit from storage at +2°C/+8°C and take out the required reagents. Carefully reseal the SPR pouch
and return the kit to +2°C/+8°C. The reagents can be used immediately.
2. Insert the "TBRA" SPR devices and "TBRA" strips into the instrument. Check to make sure the color labels with the
assay code on the SPR devices and the Reagent Strips match.
3. Mix the stimulation reagents (NIL, AG, MIT) using a vortex‑type mixer.
4. Open the stimulation reagent vials gently to avoid projections, and in the following order: NIL, then AG, then MIT.
The stimulation reagent vials must be opened away from other opened stimulation reagent vials to avoid
contamination.
5. Ensure that the stimulation reagents are free of bubbles.
6. Load the stimulation reagents.
7. Mix gently the blood samples by at least 10 tube inversions until homogenized. Do not mix with a vortex‑‑type
mixer.
8. Check the absence of films, clots, bubbles, and foam in the sample tubes.
9. Load open sample tubes.
10. For this test, the sample test portion is 3 x 300 µL.
11. Initiate the assay as directed in the User Manual. All the assay steps are performed automatically by the instrument.
12. The stimulation reagent and sample distribution will be completed within approximately 14 minutes per
patient sample.
13. After the software has authorized unloading, unload and close the stimulation reagent vials (NIL → AG → MIT) and
sample tubes, and return them to the required temperature. Note: refer to the section Warnings and Precautions for
reuse of pierced strips and SPR devices after system error.
14. The assay will be completed within approximately 17 hours for the patient sample. Do not open the section
for the duration of the test.
15. After the assay is completed, remove the Solid Phase Receptacles (SPR) and strips from the instrument.
16. Dispose of the used Solid Phase Receptacles (SPR) and strips into an appropriate recipient.
QUALITY CONTROL
Additional quality controls can be performed in accordance with local regulations or requirements related to accreditation,
as well as requirements defined in the laboratory’s quality control procedure.
Note: It is the responsibility of the user to perform Quality Control in accordance with any applicable local regulations.
RESULTS AND INTERPRETATION
Once the assay is completed, results are analyzed automatically by the computer. Fluorescence is measured twice in the
Reagent Strip’s reading cuvette for each sample tested. The first reading is a background reading of the substrate
cuvette before the SPR device is introduced into the substrate.
The second reading is taken after incubating the substrate with the enzyme that may be bound to the interior of the SPR
device. The RFV (Relative Fluorescence Value) is calculated by subtracting the background reading from the final result.
At the end of the assay, the signal results are stored in the software.
Metrological traceability
The VIDAS® TB‑IGRA assay is calibrated against WHO International Standard for Recombinant Human Interferon
Gamma (rHuIFN‑γ) No. Gxg01-902-535.
The instrument displays the VIDAS® TB‑IGRA assay results from 0.00 to 8.00 IU/mL.
The patient results are interpreted by the VIDAS® 3 system as follows:
• The RFV of a test (NIL, AG, and MIT) is mathematically placed on a Calibration Curve.
• The NIL, AG-NIL, and MIT-NIL concentrations in IU/mL, and the final clinical interpretation are indicated on the result
sheet.

Cut-off values and interpretation of results

Interpretation of results according to test value is as follows:

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NIL (IU/mL)(1) AG-NIL (IU/mL)(1) MIT-NIL Interpretation Clinical significance

(IU/mL)(1)
≥ 0.35 and ≥ 25% NIL Any Positive M. tuberculosis infection likely
< 0.35 ≥ 1.1 Negative M. tuberculosis infection NOT likely
< 6.40 or
INDETERMINATE Likelihood of M. tuberculosis infection
< 1.1
≥ 0.35 and < 25% NIL MIT Low(2) cannot be determined
INDETERMINATE NIL Likelihood of M. tuberculosis infection
≥ 6.40 Any
High(2) cannot be determined

(1) Values > 8.00 IU/mL are reported by the VIDAS® software as 8.00 IU/mL, with no impact on test results.
(2) Please refer to the following table for further information:
Interpretation Possible explanations Solutions/actions
Blood sample storage and handling
Collect a new sample and test as
may not have been implemented
instructed.
correctly.
INDETERMINATE MIT Low
The patient’s immune response may
A new test is likely to give the same
not be sufficient to generate a result
interpretation.
with the VIDAS® TB‑IGRA assay.
Blood sample may have been Collect a new sample and test as
contaminated. instructed.
Stimulation reagents may have been Discard vials and reconstitute new
contaminated during reconstitution or vials as instructed. Proceed to a new
INDETERMINATE NIL High
manipulation. test, using a new sample.
The patient’s immune response may
A new test is likely to give the same
generate a high interferon gamma
interpretation.
response.

These results are uncommon (see Table 12: Indeterminate Results) and may be related either to the immune status of
the individual tested or to a technical issue (for instance, inappropriate sample or stimulation reagent handling/storage).
LIMITATIONS OF THE METHOD
• Interference may be encountered with certain samples containing antibodies directed against reagent components.
For this reason, assay results should be interpreted taking into consideration the patient's clinical history and the
results of any other tests performed.
• Any results that do not correspond to the patient's clinical history may be due to inadequate instrument maintenance
(see the Instrument User Manual).
• Any results that do not correspond to the patient's clinical history may be due to inadequate sample preparation or
handling (see Samples section), or inadequate handling of stimulation reagents (see Reconstitution of Reagents
section).
• Results obtained from patients who have impaired or altered immune functions, such as those described below, must
be interpreted with caution:
◦ Blood samples from patients who have HIV infection or AIDS,
◦ Blood samples from patients who have transplantation managed with immunosuppressive treatment, or others
who receive immunosuppressive drugs (e.g., corticosteroids, methotrexate, azathioprine, cancer chemotherapy),
◦ Blood samples from patients who have other clinical conditions, such as diabetes, silicosis, chronic renal failure,
and hematological disorders (e.g., leukemia and lymphomas),
◦ Blood samples from patients with other specific malignancies (e.g., carcinoma of the head and neck or lung
cancer).

Additionally, the performance characteristics of the test in these populations have not been extensively evaluated.
• The performance characteristics of the test have not been extensively evaluated in individuals younger than age
18 years (please refer to the Clinical Performance section).
• Results obtained using samples from pregnant women and young patients (< 2 years of age) must be interpreted
with caution, as the performance characteristics of the test in these populations have not been evaluated.
• If the clinical status is « INDETERMINATE MIT Low » or « INDETERMINATE NIL High », result values NIL, AG-NIL,
and MIT-NIL cannot be used.

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• The antigens present in the AG stimulation reagent are derived from the M. tuberculosis proteins ESAT‑6 (6‑kDa
Early Secreted Antigen Target) and CFP‑10 (Culture Filtrate Protein‑10) which are absent in BCG strains and most
species of NTM (non‑tuberculous mycobacteria). However, M. marinum, M. kansasii, M. szulgai, M. flavescens, and
M. leprae contain homologues of ESAT‑6 and CFP‑10 and therefore could cause positive results with the VIDAS®
TB‑IGRA assay.10-13 NTM infections have not been extensively studied for cross-reactivity with the VIDAS® TB IGRA
assay. However, seven patients infected with either M. kansasii (1), M. avium (3), M. intracellulare (2), or
M. chelonae (1) were tested by collecting three samples per patient. Out of the 21 samples tested, only one sample
from a patient infected with M. intracellulare gave a positive result close to the cut‑off. All other patients had negative
results for all samples tested (20/21).

PERFORMANCE
Studies performed using the VIDAS® TB‑IGRA assay gave the following results.
Analytical Measuring Interval (AMI)
The Analytical Measuring Interval (AMI) is the range of values corresponding to the acceptable performance limits
(precision and linearity).
The AMI of the VIDAS® TB‑IGRA assay is 0.10 IU/mL to 8.00 IU/mL.
Linearity
Linearity was evaluated according to CLSI EP06-A recommendations.
The VIDAS® TB‑IGRA assay is linear between 0.10 IU/mL and 8.00 IU/mL.
Detection limits
Limit of Blank (LoB) 0.06 IU/mL
Limit of Detection (LoD) 0.08 IU/mL
Limit of Quantitation (LoQ) 0.10 IU/mL

LoB, LoD and LoQ values were determined according to CLSI EP17-A2 recommendations.
The Limit of Blank (LoB) is the concentration below which 95% of analyte-free samples are found.
The Limit of Detection (LoD) is the lowest concentration of analyte in a sample that can be distinguished from the
analyte-free sample with a probability of 95% (observed result greater than the LoB with a 95% probability).
The Limit of Quantitation (LoQ) is the lowest concentration of analyte that can be detected and measured with an
acceptable level of precision. For the VIDAS® TB-IGRA assay, the acceptable level of precision corresponds to within-lot
precision fixed at 20% CV.
Hook effect
No hook effect was found up to IFN‑γ concentrations of 150 000 IU/mL.
Analytical precision
An analytical precision study was performed according to CLSI EP05-A3 recommendations. This precision study only
evaluated precision for the IFN‑γ assay within VIDAS® TB‑IGRA.
A panel of spiked plasma samples representing different IFN‑γ levels of concentration in the AMI was analyzed on the
VIDAS® 3 instrument to include the following main sources of variability: repeatability, run, day, calibration, lot and
instrument.
Repeatability (within-lot, within-run, within-instrument precision) was estimated for each sample.
Reproductibility (between-run, between-day, between-calibration, between-lot, between-instrument precision) was
estimated for each sample.
The precision estimates obtained with the VIDAS® 3 instrument are reported in the following table, as a guide.
Sample N Mean Repeatability Between-day Between-lot precision Between-instrument
(IU/mL) Within-run precision precision precision

Standard CV (%) Standard CV (%) Standard CV (%) Standard CV (%)

Deviation Deviation Deviation Deviation
TBRA0001 144 0.15 0.01 6.0 0.01 6.9 0.02 10.4 0.02 10.4
TBRA0008 144 0.18 0.01 6.7 0.01 6.7 0.02 9.9 0.02 9.9
TBRA0002 144 0.26 0.02 6.0 0.02 6.2 0.02 8.4 0.02 8.4
TBRA0003 144 0.39 0.02 4.0 0.02 4.9 0.02 6.2 0.02 6.2

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Sample N Mean Repeatability Between-day Between-lot precision Between-instrument

(IU/mL) Within-run precision precision precision

Standard CV (%) Standard CV (%) Standard CV (%) Standard CV (%)

Deviation Deviation Deviation Deviation
TBRA0004 144 0.91 0.03 3.5 0.04 3.9 0.05 5.0 0.05 5.0
TBRA0005 144 1.82 0.07 3.8 0.08 4.2 0.10 5.5 0.10 5.6
TBRA0006 142 3.38 0.14 4.0 0.17 5.1 0.20 6.0 0.20 6.0
TBRA0007 144 7.05 0.33 4.6 0.35 5.0 0.50 7.1 0.50 7.1

Analytical specificity
Cross-reactivity
The analytical specificity of the VIDAS® TB‑IGRA assay was established by testing cross-reactive compounds according
to CLSI document EP7-Ed3 recommendations.
Cross-reactivity was evaluated by spiking plasma samples with a dose value of 0.30 IU/mL and 5.00 IU/mL of IFN‑γ with
cross-reactive compounds.
The results of this study are reported in the following table.
Tested substance Tested concentration Cross-reactivity %
ng/mL
IL2 10
IL4 5
IL5, IL6, IL10, IL12 100 No interference observed up to
TNF‑α 5 the concentration tested
IFN‑α, IFN‑β 50
IL1α, IL1β, IL3 100

Study of drugs and other potentially interfering substances

The potential interference by commonly used drugs has not been tested (please refer to the Limitations of the Method
section).
The potential interference by other substances was studied according to CLSI EP7-Ed3 recommendations.
Interference was evaluated by spiking plasma samples with a dose value of 0.3 IU/mL and 5 IU/mL of IFN‑γ with cross-
reactive compounds.
No significant interference was detected up to the concentrations indicated below:
Tested substance Maximum concentration
Hemoglobin 10 g/L (620 µmol/L)
Human Albumin 60 g/L
Triglycerides 30 g/L
Bilirubin (conjugated) 0.4 g/L (475 μmol/L)
Bilirubin (unconjugated) 0.4 g/L (684 μmol/L)
Total proteins 93 g/L
Human Anti Mouse Antibodies (HAMA) 2 µg/mL
Rheumatoid factor 800 IU/mL

By design and due to the stimulation step, the results may be impacted by factors and/or drugs that can either diminish
the number of circulating T cells, or decrease the reactivity of T cells.
CLINICAL PERFORMANCE
The clinical performance characteristics of the VIDAS® TB-IGRA assay were evaluated on two populations: a) patients
with active TB (ATB) and b) persons at mixed risk of Mtb infection (MRTI) (see Table 1).
The QuantiFERON®‑TB Gold Plus assay (QFT®‑Plus) was used as the comparative assay.

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There is no reference method or gold standard test for the diagnosis of latent TB infection (LTBI) while culture is
recognized as the gold standard for active TB. Consequently:
• Sensitivity was estimated in the Active TB population.
• Negative Percent Agreement (NPA) and Positive Percent Agreement (PPA) relative to the QFT®‑Plus assay
were estimated in the Mixed Risk population.
• A Specificity-like performance (specificity hereafter) was estimated using data from blood donors recruited in a low
endemic area. Although it is not possible to rule out latent TB infection with absolute certainty, these individuals can
be considered at an extremely low risk level of TB exposure.

Table 1: Overview of the VIDAS® TB-IGRA assay clinical performance evaluation

Population Performance Description of the population

Active TB (ATB)
Mixed Risk of Mtb
infection (MRTI)
Subpopulation: blood
donors
Sensitivity Culture-confirmed active TB patients
NPA* and PPA* Several groups of subjects with or without risk factors for Mtb
infection, ranked along a gradient of TB-exposure risk
Specificity Blood donors (extremely low TB-exposure risk)

*Relative to QFT®‑Plus (with ELISA by QIAGEN®)

1. Sensitivity in the Active TB Population
Sensitivity of the VIDAS® TB‑IGRA assay was evaluated on 200 culture-confirmed active TB patients recruited from
10 sites across the world, in low TB-incidence countries (France, UK, Italy, USA) and high TB-incidence countries (South
Africa and Mexico). Study participants were HIV‑negative and had no more than 15 days of anti‑TB treatment at the time
of blood collection.
Samples from each patient were tested in single replicate with the VIDAS® TB‑IGRA and QFT®‑Plus assays.
Sensitivity was 97.5% (193/198) for the VIDAS® TB‑IGRA assay and 80.7% (146/181) for the QFT®‑Plus assay (see
Table 2).
The VIDAS® TB‑IGRA assay gave more true‑positive results, fewer false‑negative results, and fewer indeterminate
results than the QFT®‑Plus assay.

Table 2: Sensitivity on Active TB patients

VIDAS® TB‑IGRA QFT®-Plus

Positive 193 146
Negative 5 35
Total* 198 181
Indeterminate 2 19
Sensitivity* 97.5% 80.7%
[95%CI] (193/198) (146/181)
[94.2;99.2]% [74.3;85.8]%
PPA** 99.3%
[95%CI] (143/144)
[96.2;100.0]%

*Excluding indeterminate results. See Table 12 for details.

**Positive Percent Agreement between VIDAS® 3 and QFT®‑Plus estimated on the patients with a positive QFT®‑Plus
result. Excluding indeterminate results.
[95%CI]: 95% Confidence Interval.
2. Percent Agreements in the Mixed Risk Population and Specificity in Blood Donors
Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) relative to the QFT®‑Plus assay were
estimated in the Mixed Risk population.

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The Mixed Risk population includes 1460 subjects from 18 sites across the world, in low TB‑incidence countries (France,
UK, Italy, USA) and high TB‑incidence countries (South Africa and Mexico). Most of the study participants in low
TB‑incidence countries were being tested for LTBI as part of their standard of care at the time of recruitment. The Mixed
Risk population is composed of several subgroups with or without risk factors for Mtb infection, ranked along a gradient
of TB‑exposure risk. See Table 3 for demographic details.

Table 3: Mixed Risk population - Demographics Factors

Mixed Risk population (N=1459)* Number (%) / Statistics

Gender Female 946 (64.8%)
Male 513 (35.2%)
Age (years) Range 5-88
Mean 38
BCG vaccinated Yes 533 (36.5%)
No 627 (43.0%)
Unknown 299 (20.5%)
HIV positive** Yes 22 (1.5%)
No 1209 (82.9%)
Unknown 228 (15.6%)

*Excluding indeterminate results. See Table 12 for details.

**No performance were estimated for the HIV-positive subgroup due to the low frequency.
Samples from each patient were tested in single replicate with the VIDAS® TB‑IGRA and QFT®‑Plus assays.
The VIDAS® TB‑IGRA assay gave more positive results (see Table 4 and Table 5). The rate of positive results was
statistically higher (α=5%) for the VIDAS® TB‑IGRA assay than for the QFT®‑Plus assay (p‑value < 0.0001).

Table 4: Results of the VIDAS® TB‑‑IGRA and QFT®‑Plus assays in the Mixed Risk population

Results Mixed Risk population (N=1460)

VIDAS® TB‑IGRA QFT®-Plus
Positive 343 242
(23.5%) (16.6%)
Negative 1117 1217
(76.5%) (83.4%)
Indeterminate* 0 1
(0.0%) (0.1%)

*Indeterminate results are excluded from all NPA/PPA computations.

Table 5: Contingency table between VIDAS® TB‑IGRA and QFT®‑Plus assays in the Mixed Risk population

QFT®-Plus
Negative Positive Total*
VIDAS® TB‑IGRA Negative 1097 19 1116
Positive 120 223 343
Total* 1217 242 1459

*Excluding indeterminate results. See Table 12 for details.

In the Mixed Risk population, NPA was 90.1% (1097/1217) and PPA was 92.1% (223/242) excluding any indeterminate
result (see Table 6).

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Table 6: Negative Percent Agreement (NPA) and Positive Percent Agreement (PPA) between the VIDAS® TB‑‑IGRA
and the QFT®‑Plus assays estimated on the Mixed Risk population

NPA* 90.1%
[95%CI] [88.3 ; 91.7]%
PPA* 92.1%
[95%CI] [88.1 ; 94.9]%

*Excluding indeterminate results. See Table 12 for details.

Specificity, estimated on data from blood donors, was 97.6% (122/125) for the VIDAS® TB‑IGRA assay and 95.2%
(119/125) for the QFT®‑Plus assay (see Table 7).

Table 7: Specificity on blood donors

VIDAS® TB-IGRA QFT®-Plus

Positive 3 6
Negative 122 119
Total* 125 125
Indeterminate 0 0
Specificity 97.6% 95.2%
[95%CI] (122/125) (119/125)
[93.1 ; 99.5]% [89.8 ; 98.2]%

*Excluding indeterminate results. See Table 12 for details.

Subgroups in the Mixed Risk population – Description and clinical performance

The Mixed Risk population was composed of different subgroups that can be ranked along a gradient of TB‑exposure
risk (see Table 8). The TB‑exposure risk is expected to reflect the likelihood of latent infection, i.e. the higher the risk, the
larger the expected percentage of subjects with LTBI. Therefore, a subgroup analysis was performed to evaluate the
impact of the TB‑exposure risk on the NPA and PPA of the VIDAS® TB‑IGRA assay relative to the QFT®‑Plus assay.

Table 8: Subgroups in the Mixed Risk population and their TB-exposure risk level

TB-exposure risk Subgroups Number of subjects (%)

Extremely low Blood donors without known TB-exposure risk factors 125 (8.6%)
Persons without known TB-exposure risk factors who are
Very low 90 (6.2%)
screened for LTBI due to immunosuppressive therapy
Medical students in low TB-burden countries without known
Low 118 (8.1%)
TB-exposure risk factors
Healthcare workers or volunteers without known TB-exposure
Medium Low 598 (41.0%)
risk factors
Medium Persons from TB-related settings in low TB-burden countries 13 (0.9%)
• Immigrants or residents of countries with high TB
incidence
Medium High • Persons who spent > 1 month in an area with high TB 68 (4.7%)
incidence

High TB-case contacts (non-household) 296 (20.3%)

Very high TB-case contacts (same house) 81 (5.6%)
Extremely high TB-case contacts (same bedroom) 70 (4.8%)

The VIDAS® TB‑IGRA and QFT®‑Plus results for each subgroup are reported in Table 9.
The rate of positive results with either assay tends to increase as the exposure risk increases, reflecting the expected
likelihood of LTBI in the different subgroups.

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Table 9: VIDAS® TB-IGRA and QFT®‑Plus assay results per subgroup of the Mixed Risk population

Negative results Positive results

Number of
TB-exposure risk Number (%) Number (%)
subjects
VIDAS® TB-IGRA QFT®-Plus VIDAS® TB-IGRA QFT®-Plus
Extremely low 125 122 (97.6%) 119 (95.2%) 3 (2.4%) 6 (4.8%)
Very low 90 80 (88.9%) 84 (93.3%) 10 (11.1%) 6 (6.7%)
Low 118 113 (95.8%) 117 (99.2%) 5 (4.2%) 1 (0.8%)
Medium Low 598 553 (92.5%) 593 (99.2%) 45 (7.5%) 5 (0.8%)
Medium 13 12 (92.3%) 13 (100.0%) 1 (7.7%) 0 (0.0%)
Medium High 68 28 (41.2%) 31 (45.6%) 40 (58.8%) 37 (54.4%)
High 296 152 (51.4%) 184 (62.2%) 144 (48.6%) 112 (37.8%)
Very high 81 36 (44.4%) 45 (55.6%) 45 (55.6%) 36 (44.4%)
Extremely high 70 20 (28.6%) 31 (44.3%) 50 (71.4%) 39 (55.7%)

In addition, NPA and PPA were calculated for all levels of TB‑exposure risk. As shown in Table 10, the degree of
agreement of the VIDAS® TB‑IGRA assay relative to the QFT®‑Plus assay varies depending on the risk-level. As the
TB‑exposure risk increases, NPA tends to decrease, while PPA tends to increase.
Looking at the values for the main levels of TB‑exposure risk (see Table 11 and Figure 1):
• When the TB‑exposure risk is low, i.e. LTBI is expected to be less frequent:
◦ Most of the QFT®‑negative subjects were also VIDAS®‑negative, leading to 96.9% NPA.
◦ Approximatively one third of the QFT®‑positive subjects were still VIDAS®‑negative, leading to 61.5% PPA.
• When the TB‑exposure risk is high, i.e. LTBI is expected to be more frequent:
◦ Most of the QFT®‑positive subjects were also VIDAS®‑positive, leading to 95.7% PPA.
◦ Approximatively one fourth of the QFT®‑negative subjects were still VIDAS®‑positive, leading to 76.9% NPA.

Table 10: Negative and Positive Percent Agreements estimated on the Mixed Risk population subgroups

QFT®‑Plus Negative Results QFT®‑Plus Positive Results

®
VIDAS TB-IGRA VIDAS® TB-IGRA
TB-exposure risk N NPA N PPA
Results Results
Total [95%CI] Total [95%CI]
Negative Positive Positive Negative
100.0% 50.0%
Extremely low 119 119 0 [96.9 ; 100.0]% 6 3 3 [18.8 ; 81.2]%
92.9% 66.7%
Very low 84 78 6 [85.3 ; 96.7]% 6 4 2 [30.0 ; 90.3]%
96.6% 100.0%
Low 117 113 4 [91.5 ; 99.1]% 1 1 0 [2.5 ; 100.0]%
92.7% 40.0%
Medium Low 593 550 43 [90.4 ; 94.6]% 5 2 3 [11.8 ; 76.9]%
92.3%
Medium 13 12 1 [66.7 ; 98.6]% 0 N/A N/A N/A

80.6% 91.9%
Medium High 31 25 6 [63.7 ; 90.8]% 37 34 3 [78.7 ; 97.2]%
78.3% 92.9%
High 184 144 40 [71.8 ; 83.6]% 112 104 8 [86.5 ; 96.3]%
80.0% 100.0%
Very high 45 36 9 [66.2 ; 89.1]% 36 36 0 [90.3 ; 100.0]%
64.5% 100.0%
Extremely high 31 20 11 [46.9 ; 78.9]% 39 39 0 [91.0 ; 100.0]%

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Table 11: Negative and Positive Percent Agreements estimated in the Mixed Risk Population for the main levels
of TB‑‑exposure risk

QFT®‑Plus Negative Results QFT®‑Plus Positive Results

®
VIDAS TB-IGRA VIDAS® TB-IGRA
TB-exposure risk N NPA N PPA
Results Results
Total [95%CI] Total [95%CI]
Negative Positive Positive Negative
96.9% 61.5%
Low 320 310 10 [94.3 ; 98.5]% 13 8 5
[35.5 ; 82.3]%

92.2% 85.7%
Medium 637 587 50 [89.8 ; 94.0]% 42 36 6
[72.2 ; 93.3]%

76.9% 95.7%
High 260 200 60 [71.4 ; 81.6]% 187 179 8
[91.7 ; 98.1]%

Figure 1: NPA and PPA in the Mixed Risk population for the main levels of TB‑exposure risk

3. Indeterminate Results
The frequency of indeterminate results was different in the two populations. Data are summarized in Table 12.

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Table 12: Indeterminate Results

Active TB MRTI All cohorts

(N=200) (N=1460) (N=1660)
Number % Number % Number %
®
VIDAS TB‑IGRA 2 1.0 0 0.0 2 0.1*
QFT ‑Plus
®
19 9.5 1 0.1 20 1.2*

*The rate of indeterminate results was statistically lower (α = 5%) for the VIDAS® TB‑IGRA assay than for the QFT®‑Plus
assay (p‑value = 0.0001).
The two indeterminate results observed for the VIDAS® TB‑IGRA assay were due to a high NIL value. The
20 indeterminate results observed for the QFT®‑Plus assay were all due to a low MIT-NIL value.
4. Distribution of Observed Values per Population obtained with the VIDAS® TB‑‑IGRA assay
Different levels of IFN-γ were measured in the different populations. Levels observed for NIL, AG‑NIL and MIT‑NIL are
reported in Figures 2, 3, and 4. These may be considered as typical values for the different populations.

Figure 2: Distribution of NIL values obtained with the VIDAS® TB‑IGRA assay

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Figure 3: Distribution of AG‑‑NIL values obtained with the VIDAS® TB‑IGRA assay

Figure 4: Distribution of MIT-NIL values obtained with the VIDAS® TB‑IGRA assay

5. Reproducibility of the qualitative results / Precision

The precision of the VIDAS® TB‑IGRA assay was evaluated with a multi‑center study. Samples were collected at three
different sites and tested in three different laboratories. Tests were performed by multiple operators using three different
product batches of the VIDAS® TB‑IGRA assay on three different instruments.
A total of 55 subjects were included, comprising healthcare workers, patients with suspicion of TB disease or with a
history of positive TB‑related test. Subjects that may have negative and positive results were recruited in order to cover
the measuring interval of the assay.
Six tubes of blood and up to six results were obtained for each subject. Subjects with less than four results were
excluded from data analysis. A status was attributed to each subject as follows:

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• Concordant positive if at least four samples tested positive,

• Concordant negative if at least four samples tested negative,
• Discordant if less than four concordant results were obtained.

No indeterminate results were observed.

The percentage of subjects with concordant status was 98.2% (54/55); 35 subjects were concordant negative, 19 were
concordant positive and 1 was discordant.
In total, 323 samples were analyzed and 94.4% (305/323) were concordant with the subject status. See Table 13 for
more details.

Table 13: Precision study summary

Number of samples Number of samples

Subject status Concordant/total Number of subjects
tested concordant with status
6/6 30 180 180
5/6 2 12 10
Concordant negative
4/6 1 6 4
4/5 2 10 8
6/6 13 78 78
5/6 1 6 5
Concordant positive 4/6 2 12 8
4/5 1 5 4
4/4 2 8 8
Discordant 3/6 1 6 N/A
Total 55 323 305

WASTE DISPOSAL
Dispose of used or unused reagents, as well as any other contaminated disposable materials, following procedures for
infectious or potentially infectious products.
It is the responsibility of each laboratory to handle waste and effluents produced, according to their nature and degree of
hazardousness, and to treat and dispose of them (or have them treated and disposed of) in accordance with any
applicable regulations.
LITERATURE REFERENCES
1. World health statistics 2018: monitoring health for the SDGs sustainable development goals. GWHO 2018, IGO
LCB‑N‑S 3. Who Report 2018.
2. N.M. Parrish, J.D. Dick and W.R. Bishai - Mechanisms of latency in Mycobacterium tuberculosis - Trends Microbiol.
6(3) (1998) 107–112.
3. Y. Zhang - Persistent and dormant tubercle bacilli and latent tuberculosis - Front Biosci 9 (2004) 1136–1156.
4. P. Piccini, et al. - Clinical peculiarities of tuberculosis - BMC Infect Dis [Internet] 2014;14(Suppl1):S4.
5. T. Mori et al. - Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens - Am
J Respir Crit Care Med. 2004 Jul 1;170(1): 59-64.
6. L.Richeldi - An update on the diagnosis of tuberculosis infection - Am J Respir Crit Care Med. 2006 Oct 1; 174(7):
736-42
7. WORLD HEALTH ORGANIZATION, Latent TB Infection: Updated and consolidated guidelines for programmatic
management, 2018, WHO/CDS/TB/2018.4.
8. G.Sulis et al - Recent developments in the diagnosis and management of tuberculosis - NPJ Prim Care Respir Med.
2016; 26: 16078.
9. WORLD HEALTH ORGANIZATION, USE OF ANTICOAGULANTS IN DIAGNOSTIC, LABORATORY
INVESTIGATIONS, 2002, WHO/DIL/LAB/99.1 Rev.2
10. Andersen, P. et al. - Specific immune-based diagnosis of tuberculosis - Lancet. (2000) 356(9235): 1099-1104.
11. Geluk, A. et al. - Identification and characterization of the ESAT‑6 homologue of Mycobacterium leprae and T‑cell
cross-reactivity with Mycobacterium tuberculosis - Infect Immun (2002) 70(5): 2544-2548.
12. Geluk, A. et al. - Immunological crossreactivity of the Mycobacterium leprae CFP‑10 with its homologue in
Mycobacterium tuberculosis - Scand J Immunol (2004) 59(1): 66-70.

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13. Van Ingen, J. et al. - Region of difference 1 in nontuberculous Mycobacterium species adds a phylogenetic and
taxonomical character - J Bacteriol (2009) 191(18): 5865-5867.
INDEX OF SYMBOLS
Symbol Meaning
Catalogue number

In Vitro Diagnostic Medical Device

Manufacturer

Temperature limit

Use by date

Batch code

Consult Instructions for Use

Contains sufficient for <n> tests

Date of manufacture

LIMITED WARRANTY
bioMérieux warrants the performance of the product for its stated intended use provided that all procedures for usage,
storage and handling, shelf life (when applicable), and precautions are strictly followed as detailed in the instructions for
use (IFU).
Except as expressly set forth above, bioMérieux hereby disclaims all warranties, including any implied warranties of
merchantability and fitness for a particular purpose or use, and disclaims all liability, whether direct, indirect or
consequential, for any use of the reagent, software, instrument and disposables (the "System") other than as set forth in
the IFU.
REVISION HISTORY
Change type categories
N/A Not applicable (First publication)
Correction Correction of documentation anomalies
Technical change Addition, revision and/or removal of information related to the product
Administrative Implementation of non-technical changes noticeable to the user

Note: Minor typographical, grammar, and formatting changes are not included in the revision
history.

Release Date Part Number Change Type Change Summary

2021-02 053331-01 N/A Not applicable (First publication)
2021-04 053331-02 Technical change Intended Use
Summary and Explanation
Samples
Procedure \ Launching a sample analysis
Limitations of the Method
Clinical Performance

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BIOMERIEUX, the BIOMERIEUX logo, SPR and VIDAS are used, pending, and/or registered trademarks belonging to
bioMérieux, or one of its subsidiaries or one of its companies.
QuantiFERON and QFT are registered or registration-pending trademarks of the QIAGEN Group.
CLSI is a trademark belonging to Clinical Laboratory and Standards Institute, Inc.
Any other name or trademark is the property of its respective owner.

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