ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Helicobacter Test INFAI 75 mg powder for oral solution
2.
One
jar contains 75 mg of
13
C-urea powder.
For a full list of excipients, see section 6.1.
3.
Powder for oral solution.
Clear, colourless solution.
4.
Helicobacter Test INFAI may be used for
in vivo
diagnosis of gastroduodenal
Helicobacter pylori
infection in:
-
adolescents, who are likely to have peptic ulcer disease.
This medicinal product is for diagnostic use only.
This medicinal product should be administered by a healthcare professional and under appropriate
medical supervision.
Helicobacter Test INFAI is a breath test for single administration. Patients from the age of 12 must
take the content of 1 jar with 75 mg.
For performance of the test, 200 ml 100 % orange juice or 1 g citric acid in 200 ml water for patients
from the age of 12 and older (as a pre-administered test meal), as well as tap water (for dissolving the
13
C-urea powder) are necessary.
The patient must have fasted for over 6 hours, preferably overnight. The test procedure takes
approximately 40 minutes.
In case it is necessary to repeat the test procedure, this should not be done until the following day.
The suppression of
Helicobacter pylori
might give false negative results. Therefore the test shall be
used after at least four weeks without systemic antibacterial therapy and two weeks after last dose of
acid antisecretory agents. Both might interfere with the
Helicobacter pylori
status. This is especially
important after Helicobacter eradication therapy.
It is important to follow the instructions for use adequately (see section 6.6), otherwise the reliability
of the outcome will become questionable.
2
-
adults,
4.3
The test must not be used in patients with documented or suspected gastric infection or atrophic
gastritis, which might interfere with the urea breath test (see section 4.2).
4.4
A positive test alone does not constitute indication for eradication therapy. Differential diagnosis with
invasive endoscopic methods might be indicated in order to examine the presence of any other
complicating conditions, e.g. ulcer, autoimmune gastritis and malignancies.
There is insufficient data on the diagnostic liability of the Helicobacter Test INFAI to recommend its
use in patients with gastrectomy.
For children from the age of 3, Helicobacter Test INFAI for children aged 3 to 11 is available.
In individual cases of A-gastritis (atrophic gastritis) the breath test may have false positive results;
other tests may be required to confirm the
Helicobacter pylori
status.
If the patient vomits during the test procedure, necessitating the repetition of the test, this should be
done in fasted condition and not before the following day (see section 4.2).
Helicobacter Test INFAI will be affected by all treatments interfering with
Helicobacter pylori
status
or urease activity.
It is not expected that the test procedure may be harmful during pregnancy or lactation.
It is recommended to take notice of the product information of eradication therapy products for their
use during pregnancy and lactation.
Helicobacter Test INFAI has no influence on the ability to drive and use machines.
None known.
4.9
Due to the fact that only 75 mg of
13
C-urea is delivered, an overdose is not expected.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other diagnostic agents, ATC-code: VO4CX
For the amount of 75 mg
13
C-urea, which is administered per unit in the course of the breath test, no
pharmacodynamic activity is described.
After oral ingestion the labelled urea reaches the gastric mucosa. In the presence of
Helicobacter
pylori
the
13
C-urea is metabolised by the enzyme urease of
Helicobacter pylori
.
3
2H
2
N(
13
CO)NH
2
+ 2H
2
O
Enzyme urease
4NH
3
+ 2
13
CO
2
The carbon dioxide diffuses into the blood vessels. From there it is transported as bicarbonate into the
lung and liberated as
13
CO
2
with the exhaled air.
In the presence of bacterial urease the ratio of the
13
C/
12
C-carbon isotopes is significantly changed.
The portion of
13
CO
2
in the breath samples is determined by isotope-ratio-mass-spectrometry (IRMS)
and stated as an absolute difference (∆δ-value) between the 00-minute- and the 30-minute-values.
Urease is produced in the stomach only by
Helicobacter pylori
. Other urease producing bacteria were
seldom found in the gastric flora.
The cut off point for discriminating
Helicobacter pylori
-negative and positive patients is determined to
be ∆δ-value of 4 ‰, which means that an increase of the ∆δ-value by more than 4 ‰ indicates an
infection In comparison to bioptic diagnostics of an infection with
Helicobacter pylori
, the breath test
achieved in clinical trials on 457 patients, a sensitivity in the range of 96.5 % to 97.9 % [95 %-CI:
94.05 %-99.72 %], and a specificity range from 96.7 % to 100 %. [95 %-CI: 94.17 %-103.63 %],
whereas in clinical trials on 93 adolescents from the age 12–17, a sensitivity of 97.7 % [90 %-CI:
91.3 %], and a specificity of 96.0 % [90 %-CI: 89.7 %] were achieved.
In the absence of bacterial urease, the whole amount of the administered urea after absorption from the
gastrointestinal tract will be metabolised like the endogenous urea. Ammonia which is produced as
described above by the bacterial hydrolysis is included into the metabolism as NH
4
+
.
5.2 Pharmacokinetic properties
The orally applied
13
C-urea is metabolised to carbon dioxide and ammonia or is integrated into the
body’s own urea cycle. Any increase in
13
CO
2
will be measured by isotopic analysis.
Absorption and distribution of
13
CO
2
is faster than the urease reaction. Therefore, the rate limiting step
in the whole process is the cleavage of
13
C-urea by Helicobacter's urease.
Only in
Helicobacter pylori
- positive patients does the administration of 75 mg labelled urea lead to a
significant increase of
13
CO
2
in the breath sample within the first 30 minutes.
5.3
Preclinical safety data
No concerns in relation to the clinical use of the product.
6.
6.1
List of excipients
None.
6.2
Incompatibilities
Not applicable.
6.3
Shelf-life
3 years.
4
6.4
Special precautions for storage
Do not store above 25°C.
6.5
Nature and contents of container
A test set contains the following parts:
No.
Component
Quantity
1
Jar (10 ml volume, polystyrene with polyethylene snap cap)
containing 75 mg
13
C-urea powder for oral solution
1
2
Labelled sample glass or plastic containers for sampling, storing
and transporting the breath samples for analysis:
Sampling time: 00-minute-value
Sampling time: 30-minute-value
2
2
3
Bendable straw for collection of the breath samples into the
corresponding sample containers
1
4
Data sheet for patient documentation
1
5
Package leaflet
1
6
Page of barcode labels and sticker
1
6.6
Special precautions for disposal and other handling
1.
The test is to be performed in the presence of a qualified person.
2.
Each patient should be documented according to the provided data sheet. It is recommended to
perform the test with the patient being in a resting position.
3.
The test starts with the collection of samples for the determination of baseline-value
(00-minute-value):
•
Take the straw and the two sample tubes with the label
“Sampling time: 00-minute-value” out of the test set.
•
Remove the stopper from one of the sample tubes, unwrap the straw and place the straw
into the container.
•
Now the patient breathes gently through the straw until the inner surface of the sample
tube steams up.
•
By continuously breathing the patient must pull out the straw and immediately close the
sample tube with its stopper.
(If the sample tube remains open for more than 30 seconds, the test result might be
falsified.)
•
Hold the sample tube upright and stick the bar-code label marked “00-minute-value”
round the sample tube, so that the lines of the bar-code are horizontal.
4.
Fill up the second sample tube (Label “Sampling time: 00-minute-value”) with breath by
following the same procedure.
5.
Now 200 ml of 100 % orange juice or 1 g citric acid in 200 ml water must be drunk by the
patient without delay.
6.
Now the preparation of the test solution follows:
•
The jar labelled “
13
C-urea powder” is taken from the test set, opened, and filled up to
three quarters of its volume with tap water.
•
Close the jar and shake it carefully until all the powder is dissolved. Pour the contents
into a drinking glass.
•
Fill the
13
C-urea jar to the brim with water for a second and third time and add these
contents to the drinking glass (total volume of tap water should be approximately 30 ml).
7.
This test solution must now be drunk immediately by the patient, and the time of application
must be noted.
8.
Thirty minutes after administration of the test solution (point 7), collect the 30-minute-value
samples in the two containers which are left in the test package (Label “Sampling time: 30-
5
minute-value”), as described under steps 3 to 4. Use the bar-code labels marked “30-minute-
value” for these samples.
9. Put the relevant bar-code label on the data sheet for patient documentation. Finally seal the
package with the sticker.
10. The sample tubes have to be sent in the original packaging, for analysis, to a qualified
laboratory.
Analysis of breath samples and testing specification for laboratories
The breath samples, collected in 10 ml glass- or plastic sample tubes, are analysed by isotope ratio
mass spectrometry (IRMS).
The analysis of the
13
C/
12
C-ratio in carbon dioxide of breath is an integrated part of the diagnostic test
Helicobacter Test INFAI. The accuracy of the test strongly depends on the quality of the breath
analysis. The specification of breath analysis parameters like linearity, stability (reference gas
precision), and precision of measurement are fundamental for the accuracy of the system.
It has to be ensured that the analysis is carried out by a qualified laboratory. The method validated in
the application is as follows:
•
Sample preparation for (IRMS)
To determine the
13
C/
12
C-ratio of carbon dioxide in breath by mass spectrometric analysis the carbon
dioxide must be separated from the breath and introduced into the mass spectrometer. The automatic
preparation system for isotope mass spectrometers which is dedicated for breath test analysis is based
on a gas-chromatographic continuous flow separation technique.
Water is removed from the sample by means of a Nafion water trap or the gas-chromatographic
preparation system that separates the individual gases in a gas chromatographic column with Helium
as eluent. Passing the column the separated gas species of breath are detected by an ionisation
detector. The fraction of carbon dioxide gas, identified by its characteristic retention time, is
introduced into mass spectrometer.
•
Mass spectrometric analysis
To analyse the separated carbon dioxide sample gas its molecules must be ionised, formed into a
beam, accelerated by an electric field, deflected in a magnetic field, and finally detected. These five
processes take place in the analyser of a mass spectrometer, which consists of three separate sections:
the source, flight tube, and collector. Ionisation, beam formation and acceleration all occur in the
source, magnetic deflection takes place in the flight tube and detection takes place in the collector.
•
Sample inlet
For introduction of the carbon dioxide into the analyser many sample inlet systems are available. For
breath test analysis the individual balancing of the carbon dioxide of the sample to a reference
standard gas is essential. This ensures the high accuracy of this system, as calculation of the isotopic
content in carbon dioxide is done with respect to an independent standard.
•
Specifications for determining
13
C/
12
C-ratios
The breath test concept relies on the administration of a specifically
13
C-labelled urea whose
metabolite utilisation is monitored by measuring
13
CO
2
in the expired breath gas.
6
•
The mass spectrometer must be capable of:
Multiple replicate analyses: Minimum of 3 replicate analyses on the same sample during operation
Security access:
Storing of operating parameters and of results under security access to
avoid later manipulation
Adjustment:
13
C/
12
C-ratio with respect to Pee Dee Beliminate (PDB)
Sample loop:
< 200 µl
The principal tests to verify the specifications are linearity, stability (reference gas precision), and
precision of measurement.
•
All mass spectrometers for breath analysis must comply with the following specifications:
Linearity:
≤ 0.5 ‰ for breath samples varying between 1 % and 7 % CO
2
-
concentration
Stability:
≤ 0.2 ‰ on 10 consecutive pulses
Precision of measurement: ≤ 0.3 ‰ for
13
C at natural abundance using a 10 ml breath sample tube
with 3 % CO
2
breath concentration
Helicobacter pylori
infection is present if the difference in
13
C/
12
C of baseline-value and 30-minute-
value exceeds 4.0 ‰.
Alternatively, any other suitable-validated method may be used, carried out by any objectively
qualified laboratory.
7.
INFAI, Institut für biomedizinische Analytik & NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Germany
8.
EU/1/97/045/001
9.
Date of first authorisation:
14/08/1997
10.
7
Date of latest renewal:
14/08/2007
1.
Helicobacter Test INFAI 75 mg powder for oral solution
2.
1
jar contains 75 mg of
13
C-urea powder.
For a full list of excipients, see section 6.1.
3.
Powder for oral solution.
Clear, colourless solution.
4.
Helicobacter Test INFAI may be used for
in vivo
diagnosis of gastroduodenal
Helicobacter pylori
infection in:
-
adults,
-
adolescents, who are likely to have peptic ulcer disease.
This medicinal product is for diagnostic use only.
This medicinal product should be administered by a healthcare professional and under appropriate
medical supervision.
Helicobacter Test INFAI is a breath test for single administration. Patients from the age of 12 must
take the contents of 1 jar with 75 mg.
For performance of the test, 200 ml 100 % orange juice or 1 g citric acid in 200 ml water for patients
from the age of 12 and older (as a pre-administered test meal), as well as tap water (for dissolving the
13
C-urea powder) are necessary.
The patient must have fasted for over 6 hours, preferably overnight. The test procedure takes
approximately 40 minutes.
In case it is necessary to repeat the test procedure, this should not be done until the following day.
The suppression of
Helicobacter pylori
might give false negative results. Therefore the test shall be
used after at least four weeks without systemic antibacterial therapy and two weeks after last dose of
acid antisecretory agents. Both might interfere with the
Helicobacter pylori
status. This is especially
important after Helicobacter eradication therapy.
It is important to follow the instructions for use adequately (see section 6.6), otherwise the reliability
of the outcome will become questionable.
8
The test must not be used in patients with documented or suspected gastric infection or atrophic
gastritis, which might interfere with the urea breath test (see section 4.2).
A positive test alone does not constitute indication for eradication therapy. Differential diagnosis with
invasive endoscopic methods might be indicated in order to examine the presence of any other
complicating conditions, e.g. ulcer, autoimmune gastritis and malignancies.
There is insufficient data on the diagnostic liability of the Helicobacter Test INFAI to recommend its
use in patients with gastrectomy.
For children from the age of 3, Helicobacter Test INFAI for children aged 3 to 11 is available.
In individual cases of A-gastritis (atrophic gastritis) the breath test may have false positive results;
other tests may be required to confirm the
Helicobacter pylori
status.
If the patient vomits during the test procedure, necessitating the repetition of the test, this should be
done in fasted condition and not before the following day (see section 4.2).
Helicobacter Test INFAI will be affected by all treatments interfering with
Helicobacter pylori
status
or urease activity.
It is not expected that the test procedure may be harmful during pregnancy or lactation.
It is recommended to take notice of the product information of eradication therapy products for their
use during pregnancy and lactation.
Helicobacter Test INFAI has no influence on the ability to drive and use machines.
None known.
Due to the fact that only 75 mg of
13
C-urea is delivered, an overdose is not expected.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other diagnostic agents, ATC-code: VO4CX
For the amount of 75 mg
13
C-urea, which is administered per unit in the course of the breath test, no
pharmacodynamic activity is described.
After oral ingestion the labelled urea reaches the gastric mucosa. In the presence of
Helicobacter
pylori
the
13
C-urea is metabolised by the enzyme urease of
Helicobacter pylori
.
9
2H
2
N(
13
CO)NH
2
+ 2H
2
O
Enzyme urease
4NH
3
+ 2
13
CO
2
The carbon dioxide diffuses into the blood vessels. From there it is transported as bicarbonate into the
lung and liberated as
13
CO
2
with the exhaled air.
In the presence of bacterial urease the ratio of the
13
C/
12
C-carbon isotopes is significantly changed.
The portion of
13
CO
2
in the breath samples is determined by non-dispersive infrared spectrometry and
stated as an absolute difference (∆δ-value) between the 00-minute- and the 30-minute-values.
Urease is produced in the stomach only by
Helicobacter pylori
. Other urease producing bacteria were
seldom found in the gastric flora.
The cut off point for discriminating
Helicobacter pylori
-negative and positive patients is determined to
be ∆δ-value of 4 ‰, which means that an increase of the ∆δ-value by more than 4 ‰ indicates an
infection. In comparison to bioptic diagnostics of an infection with
Helicobacter pylori
, the breath test
achieved, in clinical trials on 457 patients, sensitivity in the range of 96.5 % to 97.9 % [95 %-CI:
94.05 % - 99.72 %], and a specificity range from 96.7 % to 100 %. [95 %-CI: 94.17 % - 103.63 %].
In the absence of bacterial urease, the whole amount of the administered urea after absorption from the
gastrointestinal tract will be metabolised like the endogenous urea. Ammonia which is produced as
described above by the bacterial hydrolysis is included into the metabolism as NH
4
+
.
5.2 Pharmacokinetic properties
The orally applied
13
C-urea is metabolised to carbon dioxide and ammonia or is integrated into the
body’s own urea cycle. Any increase in
13
CO
2
will be measured by isotopic analysis.
Absorption and distribution of
13
CO
2
is faster than the urease reaction. Therefore, the rate-limiting step
in the whole process is the cleavage of
13
C-urea by Helicobacter's urease.
Only in
Helicobacter pylori
- positive patients does the administration of 75 mg labelled urea lead to a
significant increase of
13
CO
2
in the breath sample within the first 30 minutes.
5.3 Preclinical safety data
No concerns in relation to the clinical use of the product.
6.1 List of excipients
None.
6.2 Incompatibilities
Not applicable.
6.3 Shelf-life
3 years.
6.4 Special precautions for storage
Do not store above 25°C.
10
6.5 Nature and contents of container
A test set contains 1 jar with the additional components:
No.
Component
Quantity
1
Jar (10 ml volume, polystyrene with polyethylene snap cap)
containing 75 mg
13
C-urea powder for oral solution
1
2
Breath bags:
Sampling time: 00-minute-value
Sampling time: 30-minute-value
1
1
3
Bendable straw for collection of the breath samples into the
corresponding sample bags
1
4
Data sheet for patient documentation
1
5
Package leaflet
1
6
Page of Barcode labels and sticker
1
A test set contains 50 jars with the additional components:
No.
Component
Quantity
Jar (10 ml volume, polystyrene with polyethylene snap cap)
containing 75 mg
13
C-urea powder for oral solution
1
50
2
Breath bags:
Sampling time: 00-minute-value
Sampling time: 30-minute-value
50
50
Bendable straw for collection of the breath samples into the
corresponding sample containers
3
50
4
Data sheet for patient documentation
50
5
Package leaflet
50
6
Page of barcode labels and sticker
50
6.6 Special precautions for disposal and other handling
1.
The test is to be performed in the presence of a qualified person.
2.
Each patient should be documented according to the provided data sheet. It is recommended to
perform the test with the patient being in a resting position.
3.
The test starts with the collection of samples for the determination of baseline-value
(00-minute-value):
•
Take the straw and one breath bag with the label
“Sampling time: 00-minute-value” out of the test set.
•
Remove the stopper from one of the breath bags, unwrap the straw and place the straw
into the breath bag.
•
Now the patient breathes gently through the straw.
•
By continuously breathing the patient must pull out the straw and immediately close the
breath bag with its stopper.
(If the breath bag remains open for more than 30 seconds, the test result might be
falsified.)
•
Hold the breath bag upright and stick the bar-code label marked “00-minute-value” on the
breath bag.
4.
Now 200 ml of 100 % orange juice or 1 g citric acid in 200 ml water must be drunk by the
patient without delay.
5.
Now the preparation of the test solution follows:
•
The jar labelled “
13
C-urea powder” is taken from the test set, opened, and filled up to
three quarters of its volume with tap water.
•
Close the jar and shake it carefully until all the powder is dissolved. Pour the contents
into a drinking glass.
11
•
Fill the
13
C-urea jar to the brim with water for a second and third time and add these
contents to the drinking glass (total volume of tap water should be approximately 30 ml).
6.
This test solution must now be drunk immediately by the patient, and the time of application
must be noted.
7.
Thirty minutes after administration of the test solution (point 6), collect the 30-minute-value
samples in the breath bag, which is left in the test package (Label “Sampling time: 30-minute-
value”), as described under step 3. Use the bar-code labels marked “30-minute-value” for this
sample.
8.
Put the relevant bar-code label on the data sheet for patient documentation. Finally seal the
package with the sticker.
9.
The breath bags have to be sent in the original packaging, for analysis, to a qualified laboratory.
Analysis of breath samples and testing specification for laboratories
The breath samples, collected in 100 ml breath bags, are analysed by non-dispersive infrared
spectrometry (NDIR).
The analysis of the
13
C/
12
C-ratio in carbon dioxide of breath is an integrated part of the diagnostic test
Helicobacter Test INFAI. The accuracy of the test strongly depends on the quality of the breath
analysis. The specification of breath analysis parameters like linearity, stability (reference gas
precision), and precision of measurement are fundamental for the accuracy of the system.
It has to be ensured that the analysis is carried out by a qualified laboratory. It is recommended to
measure as soon as possible after the breath collection, in any case not later than 4 weeks.
The method validated in the application is as follows:
•
Sample preparation for Infrared Spectroscopy (NDIR)
The determination of
13
C/
12
C-ratio in the carbon dioxide of the breath samples is carried out directly in
the breath. The breath from the bags will be introduced into the NDIR spectrometer using a variable
gas pump. The water content of the breath sample will be kept mostly constant through Nafion water
trap. For calibration and measurement necessary CO
2
-free air (zero-gas) will be produced via an
integrated CO
2
-absorber in the analysator.
•
Infrared spectroscopic analysis
To analyse the carbon dioxide in breath a broad band infrared radiation bunch emitted by an infrared
radiation source is alternately sent through the measuring chamber and a reference chamber by means
of a beam chopper. The modulated infrared beams then enter the infrared detectors, which are double
layer transmission detectors with a front, and a rear chamber each filled with one of the isotopicly pure
gases (
13
CO
2
or
12
CO
2
, respectively) to be measured. The infrared radiation in the measuring chamber
is weakened by the gas component to be measured. Thus the radiation equilibrium between measuring
and comparative beam is disturbed. In consequence there is a temperature fluctuation, which in its turn
causes a fluctuating pressure in the front chamber of the infrared detector. A membrane capacitor
connected with this chamber, which is exposed to a high resistance direct voltage, transforms these
pressure fluctuations into an alternating voltage, which is a measure of the isotopic composition of
breath carbon dioxide.
12
•
Sample Inlet
A semi-automatic sample inlet system injects the measuring gas in definite amounts into the zero gas
circulating in the gas circuit of the infrared spectrometer. This enables measurement of the
13
C/
12
C
ratio at any CO
2
concentration above 1 %.
•
Specifications for determining
13
C/
12
C-ratios
The breath test concept is based upon the oral administration of
13
C-labelled urea whose enzymatic
hydrolysis is monitored by measuring
13
CO
2
in breath using non-dispersive infrared spectrometry.
•
Infrared spectrometers for breath analysis must comply with the following specifications:
Multiple replicate analyses: Minimum of 3 replicate analyses of the same sample during operation
Security access:
Storing of operating parameters and of results under security access to
avoid later manipulation
For verifying the specifications linearity, stability, and precision of measurement have to be tested.
Zero point adjustment of the detectors by means of the zero gas generated in the spectrometer. End-
point adjustment of the detectors by means of calibration gases of precisely known concentration.
Linearity:
≤ 0.5 ‰ for breath samples varying between 1 % and 7 % CO
2
-
concentration
Stability: ≤ 0.3 ‰ at 10 consecutive pulses
Precision of measurement: ≤ 0.5 ‰ for
13
C at natural abundance using a 100 ml breath bag with
3% CO
2
breath concentration
Helicobacter pylori
infection is present if the difference in
13
C/
12
C of baseline-value and 30-minute-
value exceeds 4.0 ‰
.
Alternatively, any other suitable-validated method may be used, carried out by any objectively
qualified laboratory.
INFAI, Institut für biomedizinische Analytik & NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Germany
8.
MARKETING AUTHORISATION NUMBERS
EU/1/97/045/002
EU/1/97/045/004
Date of first authorisation:
14/08/1997
13
Date of latest renewal:
14/08/2007
1.
Helicobacter Test INFAI for children of the age 3-11 45 mg powder for oral solution
2.
One jar contains 45 mg of
13
C-urea powder.
For a full list of excipients, see section 6.1.
3.
Powder for oral solution.
Clear, colourless solution.
4.
Helicobacter Test INFAI for children aged 3 to 11 years may be used for
in vivo
diagnosis of
gastroduodenal
Helicobacter pylori
infection:
-
for the evalutation of the success of eradication treatment, or,
-
when there are discordant results arising from invasive tests.
This medicinal product is for diagnostic use only.
This medicinal product should be administered by a healthcare professional and under appropriate
medical supervision.
Helicobacter Test INFAI for children aged 3 to 11 years is a breath test for single administration.
Children from the age of 3 to 11 must take the content of 1 jar with 45 mg.
For performance of the test, 100 ml 100 % orange juice for patients from the age of 3 to 11 (as a pre-
administered test meal), as well as tap water (for dissolving the
13
C-urea powder) are necessary.
The patient must have fasted for over 6 hours, preferably overnight. The test procedure takes
approximately 40 minutes.
In case it is necessary to repeat the test procedure, this should not be done until the following day.
The suppression of
Helicobacter pylori
might give false negative results. Therefore the test shall be
used after at least four weeks without systemic antibacterial therapy and two weeks after last dose of
acid antisecretory agents. Both might interfere with the
Helicobacter pylori
status. This is especially
important after Helicobacter eradication therapy.
It is important to follow the instructions for use adequately (see section 6.6), otherwise the reliability
of the outcome will become questionable.
14
-
when invasive tests cannot be performed, or
4.3
The test must not be used in patients with documented or suspected gastric infection or atrophic
gastritis, which might interfere with the urea breath test (see section 4.2).
4.4
A positive test alone does not constitute indication for eradication therapy. Differential diagnosis with
invasive endoscopic methods might be indicated in order to examine the presence of any other
complicating conditions, e.g. ulcer, autoimmune gastritis and malignancies.
There is insufficient data on the diagnostic liability of the Helicobacter Test INFAI for children aged 3
to 11 years to recommend its use in patients with gastrectomy and in patients younger than 3 years of
age.
In individual cases of A-gastritis (atrophic gastritis) the breath test may have false positive results;
other tests may be required to confirm the
Helicobacter pylori
status.
If the patient vomits during the test procedure, necessitating the repetition of the test, this should be
done in fasted condition and not before the following day (see section 4.2).
Helicobacter Test INFAI for children aged 3 to 11 years will be affected by all treatments interfering
with
Helicobacter pylori
status or urease activity.
Not applicable.
None.
None known.
4.9
Due to the fact that only 45 mg of
13
C-urea is delivered, an overdose is not expected.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other diagnostic agents, ATC-code: VO4CX
For the amount of 45 mg
13
C-urea, which is administered per unit in the course of the breath test, no
pharmacodynamic activity is described.
After oral ingestion the labelled urea reaches the gastric mucosa. In the presence of
Helicobacter
pylori
the
13
C-urea is metabolised by the enzyme urease of
Helicobacter pylori
.
2H
2
N(
13
CO)NH
2
+ 2H
2
O
Enzyme urease
4NH
3
+ 2
13
CO
2
15
The carbon dioxide diffuses into the blood vessels. From there it is transported as bicarbonate into the
lung and liberated as
13
CO
2
with the exhaled air.
In the presence of bacterial urease the ratio of the
13
C/
12
C-carbon isotopes is significantly changed.
The portion of
13
CO
2
in the breath samples is determined by isotope-ratio-mass-spectrometry (IRMS)
and stated as an absolute difference (∆δ-value) between the 00-minute- and the 30-minute-values.
Urease is produced in the stomach only by
Helicobacter pylori
. Other urease producing bacteria were
seldom found in the gastric flora.
The cut off point for discriminating
Helicobacter pylori
-negative and positive patients is determined to
be ∆δ-value of 4 ‰, which means that an increase of the ∆δ-value by more than 4 ‰ indicates an
infection. In comparison to bioptic diagnostics of an infection with
Helicobacter pylori
, the breath test
achieved, in a clinical trial on 168 patients from the age of 3 to 11, a sensitivity of 98.4 % [90 %-CI:
≥ 93.9 %], and a specificity of 98.1 % [90 %-CI: ≥ 95.1 %].
In the absence of bacterial urease, the whole amount of the administered urea after absorption from the
gastrointestinal tract will be metabolised like the endogenous urea. Ammonia which is produced as
described above by the bacterial hydrolysis is included into the metabolism as NH
4
+
.
5.2 Pharmacokinetic properties
The orally applied
13
C-urea is metabolised to carbon dioxide and ammonia or is integrated into the
body’s own urea cycle. Any increase in
13
CO
2
will be measured by isotopic analysis.
Absorption and distribution of
13
CO
2
is faster than the urease reaction. Therefore, the rate limiting step
in the whole process is the cleavage of
13
C-urea by Helicobacter's urease.
Only in
Helicobacter pylori
- positive patients does the administration of 45 mg labelled urea lead to a
significant increase of
13
CO
2
in the breath sample within the first 30 minutes.
5.3
Preclinical safety data
No concerns in relation to the clinical use of the product.
6.
6.1
List of excipients
None.
6.2
Incompatibilities
Not applicable.
6.3
Shelf-life
3 years.
6.4
Special precautions for storage
Do not store above 25°C.
16
6.5
Nature and contents of container
A test set contains the following parts:
No.
Component
Quantity
1
Jar (10 ml volume, polystyrene with polyethylene snap cap)
containing 45 mg
13
C-urea powder for oral solution
1
2
Labelled sample glass- or plastic- containers for sampling, storing
and transporting the breath samples for analysis:
Sampling time: 00-minute-value
Sampling time: 30-minute-value
2
2
3
Bendable straw for collection of the breath samples into the
corresponding sample containers
1
4
Data sheet for patient documentation
1
5
Package leaflet
1
6
Page of barcode labels and sticker
1
6.6
Special precautions for disposal and other handling
1.
The test is to be performed in the presence of a qualified person.
2.
Each patient should be documented according to the provided data sheet. It is recommended to
perform the test with the patient being in a resting position.
3.
The test starts with the collection of samples for the determination of baseline-value
(00-minute-value):
•
Take the straw and the two sample tubes with the label
“Sampling time: 00-minute-value” out of the test set.
•
Remove the stopper from one of the sample tubes, unwrap the straw and place the straw
into the container.
•
Now the patient breathes gently through the straw until the inner surface of the sample
tube steams up.
•
By continuously breathing the patient must pull out the straw and immediately close the
sample tube with its stopper.
(If the sample tube remains open for more than 30 seconds, the test result might be
falsified.)
•
Hold the sample tube upright and stick the bar-code label marked “00-minute-value”
round the sample tube, so that the lines of the bar-code are horizontal.
4.
Fill up the second sample tube (Label “Sampling time: 00-minute-value”) with breath by
following the same procedure.
5.
Now 100 ml of 100 % orange juice must be drunk by the patient without delay.
6.
Now the preparation of the test solution follows:
•
The jar labelled “
13
C-urea powder” is taken from the test set, opened, and filled up to
three quarters of its volume with tap water.
•
Close the jar and shake it carefully until all the powder is dissolved. Pour the contents
into a drinking glass.
•
Fill the
13
C-urea jar to the brim with water for a second and third time and add these
contents to the drinking glass (total volume of tap water should be approximately 30 ml).
7.
This test solution must now be drunk immediately by the patient, and the time of application
must be noted.
8.
Thirty minutes after administration of the test solution (point 7), collect the 30-minute-value
samples in the two containers which are left in the test package (Label “Sampling time: 30-
minute-value”), as described under steps 3 to 4. Use the bar-code labels marked “30-minute-
value” for these samples.
9.
Put the relevant bar-code label on the data sheet for patient documentation. Finally seal the
package with the sticker.
17
10. The sample tubes have to be sent in the original packaging, for analysis, to a qualified
laboratory.
Analysis of breath samples and testing specification for laboratories
The breath samples, collected in 10 ml glass- or plastic sample tubes, are analysed by isotope ratio
mass spectrometry (IRMS).
The analysis of the
13
C/
12
C-ratio in carbon dioxide of breath is an integrated part of the diagnostic test
Helicobacter Test INFAI. The accuracy of the test strongly depends on the quality of the breath
analysis. The specification of breath analysis parameters like linearity, stability (reference gas
precision), and precision of measurement are fundamental for the accuracy of the system.
It has to be ensured that the analysis is carried out by a qualified laboratory. The method validated in
the application is as follows:
•
Sample preparation for (IRMS)
To determine the
13
C/
12
C-ratio of carbon dioxide in breath by mass spectrometric analysis the carbon
dioxide must be separated from the breath and introduced into the mass spectrometer. The automatic
preparation system for isotope mass spectrometers which is dedicated for breath test analysis is based
on a gas-chromatographic continuous flow separation technique.
Water is removed from the sample by means of a Nafion water trap or the gas-chromatographic
preparation system that separates the individual gases in a gas chromatographic column with Helium
as eluent. Passing the column the separated gas species of breath are detected by an ionisation
detector. The fraction of carbon dioxide gas, identified by its characteristic retention time, is
introduced into mass spectrometer.
•
Mass spectrometric analysis
To analyse the separated carbon dioxide sample gas its molecules must be ionised, formed into a
beam, accelerated by an electric field, deflected in a magnetic field, and finally detected. These five
processes take place in the analyser of a mass spectrometer, which consists of three separate sections:
the source, flight tube, and collector. Ionisation, beam formation and acceleration all occur in the
source, magnetic deflection takes place in the flight tube and detection takes place in the collector.
•
Sample inlet
For introduction of the carbon dioxide into the analyser many sample inlet systems are available. For
breath test analysis the individual balancing of the carbon dioxide of the sample to a reference
standard gas is essential. This ensures the high accuracy of this system, as calculation of the isotopic
content in carbon dioxide is done with respect to an independent standard.
•
Specifications for determining
13
C/
12
C-ratios
The breath test concept relies on the administration of a specifically
13
C-labelled urea whose
metabolite utilisation is monitored by measuring
13
CO
2
in the expired breath gas.
•
The mass spectrometer must be capable of:
Multiple replicate analyses: Minimum of 3 replicate analyses on the same sample during operation
Security access:
Storing of operating parameters and of results under security access to
avoid later manipulation
18
Adjustment:
13
C/
12
C-ratio with respect to Pee Dee Beliminate (PDB)
Sample loop:
< 200 µl
The principle tests to verify the specifications are linearity, stability (reference gas precision), and
precision of measurement.
•
All mass spectrometers for breath analysis must comply with the following specifications:
Linearity:
≤ 0.5 ‰ for breath samples varying between 1 % and 7 % CO
2
-
concentration
Stability:
≤ 0.2 ‰ on 10 consecutive pulses
Precision of measurement: ≤ 0.3 ‰ for
13
C at natural abundance using a 10 ml breath sample tube
with 3 % CO
2
breath concentration
Helicobacter pylori
infection is present if the difference in
13
C/
12
C of baseline-value and 30-minute-
value exceeds 4.0 ‰.
Alternatively, any other suitable-validated method may be used, carried out by any objectively
qualified laboratory.
7.
INFAI, Institut für biomedizinische Analytik & NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Germany
8.
EU/1/97/045/003
9.
Date of first authorisation:
14/08/1997
Date of latest renewal:
14/08/2007
10.
19
ANNEX II
A. MANUFACTURING AUTHORISATION HOLDER
RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
20
A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer responsible for batch release
INFAI, Institut für biomedizinische Analytik & NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Germany
B. CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
21
ANNEX III
LABELLING AND PACKAGE LEAFLET
22
A. LABELLING
23
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON, PACK OF 1 JAR AND 50 JARS
1.
Helicobacter Test INFAI 75 mg powder for oral solution
13
C-Urea
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 Jar containing 75 mg
13
C-Urea.
3.
LIST OF EXCIPIENTS
None
4.
Powder for oral solution
1 Diagnostic Test Kit contains:
1 Jar containing 75 mg
13
C-Urea powder for oral solution
4 containers for breath samples
1 bendable straw
Package Leaflet
Data sheet for patient documentation
Page of labels and sticker
1 Diagnostic Test Kit contains:
1 Jar containing 75 mg 13C-Urea powder for oral solution
2 breath bags for breath samples
1 bendable straw
Package Leaflet
Data sheet for patient documentation
Bar code labels and sticker
1 Diagnostic Test Kit contains:
50 Jars containing 75 mg 13C-Urea powder for oral solution
100 breath bags for breath samples
50 bendable straws
50 Package Leaflet
50 Data sheets for patient documentation
50 Barcode labels and sticker
24
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use
For Mass Spectrometry
For Infrared Spectroscopy
Please read enclosed instructions for use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP: {MM/YYYY}
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
25
Marketing Authorisation Holder:
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
Marketing Authorisation Number:
EU/1/97/045/001
EU/1/97/045/002
13. BATCH NUMBER
Batch:
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16.
INFORMATION IN BRAILLE
Helicobacter Test INFAI 75 mg
26
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
INTERMEDIATE CARTON, PACK SIZE 50
1.
Helicobacter Test INFAI 75 mg powder for oral solution
13
C-Urea
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 Jar containing 75 mg
13
C-Urea
3.
LIST OF EXCIPIENTS
None
4.
Powder for oral solution
CLINIPAC 50
50 Jars containing 75 mg
13
C-Urea powder for oral solution
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP: {MM/YYYY}
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
27
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
Marketing Authorisation Number:
EU/1/97/045/004
13. BATCH NUMBER
Batch:
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16.
INFORMATION IN BRAILLE
Helicobacter Test INFAI 75 mg
28
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
JAR LABEL
1.
Helicobacter Test INFAI 75 mg powder for oral solution
13
C-Urea
Oral use
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP: {MM/YYYY}
4.
BATCH NUMBER
Batch:
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
Jar contains 75 mg
13
C-Urea
6.
OTHER
Single Test
Powder for oral solution
Please read enclosed instructions for use.
Keep out of the reach and sight of children.
Do not store above 25°C.
Medicinal product subject to medical prescription.
Marketing Authorisation Number:
EU/1/97/045/001
EU/1/97/045/002
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
29
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON
1.
Helicobacter Test INFAI for children of the age 3-11 45 mg powder for oral solution
13
C-Urea
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 Jar containing 45 mg
13
C-Urea.
3.
LIST OF EXCIPIENTS
None
4.
Powder for oral solution
1 Diagnostic Test Kit contains:
1 Jar containing 75 mg
13
C-Urea powder for oral solution
4 containers for breath samples
1 bendable straw
Package Leaflet
Data sheet for patient documentation
Page of labels and sticker
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use
Please read the package leaflet before use.
30
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP: {MM/YYYY}
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Marketing Authorisation Holder:
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
Marketing Authorisation Number:
EU/1/97/045/003
13. BATCH NUMBER
Batch:
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Helicobacter Test INFAI 45 mg
31
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
JAR LABEL
1.
Helicobacter Test INFAI for children of the age 3-11 45 mg powder for oral solution
13
C-Urea
Oral use
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
EXP: {MM/YYYY}
4.
BATCH NUMBER
Batch:
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
Jar contains 45 mg
13
C-Urea
6.
OTHER
Single Test
Powder for oral solution
Please read enclosed instructions for use.
Keep out of the reach and sight of children.
Do not store above 25°C.
Medicinal product subject to medical prescription.
Marketing Authorisation Number:
EU/1/97/045/003
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
32
MINIMUM PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
BREATH SAMPLE CONTAINERS: GLASS OR PLASTIC
1.
Helicobacter Test INFAI
2.
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
3.
EXPIRY DATE
4.
BATCH NUMBER
5.
OTHER
Breath sample container
00-minute value
30-minute value
Please stick round barcode label
33
MINIMUM PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
PAGE OF LABELS AND STICKERS
1.
Helicobacter Test INFAI
2.
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
3.
EXPIRY DATE
4.
BATCH NUMBER
5.
OTHER
Page of labels and sticker
Barcode for data sheet for patient documentation
Seal-Sticker
Barcodes for 00-minute-value
Barcodes for 30-minute-value
34
B. PACKAGE LEAFLET
35
PACKAGE LEAFLET: INFORMATION FOR THE USER
Helicobacter Test INFAI 75 mg powder for oral solution
13
C-urea
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1.
What Helicobacter Test INFAI is and what it is used for
2.
Before you take Helicobacter Test INFAI
3.
How to take Helicobacter Test INFAI
5
How to store Helicobacter Test INFAI
6.
Further information
1.
WHAT HELICOBACTER TEST INFAI IS AND WHAT IT IS USED FOR
Helicobacter Test INFAI is for diagnostic use only.
Helicobacter Test INFAI is a breath test that can be used for adolescents from the age of 12 and older
and adults to determine whether or not you have an infection in the stomach caused by the bacterium
Helicobacter pylori
.
Why do you need to take the Helicobacter Test INFAI?
You may have a gastric infection caused by a bacterium called
Helicobacter pylori
. Your doctor has
recommended that you have a Helicobacter Test INFAI for one of the following reasons:
¾
Your doctor wants to confirm whether you are suffering from
Helicobacter pylori
infection to
help diagnose your condition.
¾
You have already been diagnosed as being infected with
Helicobacter pylori
and have been
taking medication aimed to clear up the infection. Your doctor now wishes to find out if the
treatment has been successful.
How does the test work?
All foods contain a substance called
13
Carbon (1 %
13
C). This
13
Carbon can be detected in the carbon
dioxide you breathe out of your lungs. The actual amount of
13
Carbon in the breath will depend on the
kind of food that you have eaten. You will be asked to drink the “test meal”. Following the meal,
samples of your breath will be taken (see “Special instructions for use”).
These samples will be analysed to measure the “normal” amount of
13
Carbon content in the carbon
dioxide in your breath.
You will then be asked to drink a solution of
13
Carbon-urea.
Further samples of your breath will then be taken 30 minutes later and the amount of
13
Carbon in the
samples measured as before. The results will be compared and a significant increase in the amount of
13
Carbon in the second set of samples will suggest your doctor that
Helicobacter pylori
are present.
36
4.
Possible side effects
2.
BEFORE YOU TAKE HELICOBACTER TEST INFAI
Please tell your doctor if you suffer from any medical condition that you think may affect, or be
affected by the test. It is also important that you tell your doctor if any of the following circumstances
apply to you:
Do not take Helicobacter Test INFAI
-
if you have or if it is suspected that you have a gastric infection or an atropic gastritis (special
form of gastritis), because this might interfere with the urea breath test.
Take special care with Helicobacter Test INFAI
Even if the result of Helicobacter Test INFAI is positive, further tests might be necessary before a
treatment of a
Helicobacter pylori
infection (eradication therapy) may be started. Various diagnostic
tests, including invasive endoscopic tests, could be required to check for the presence of any other
complications, such as gastric ulcer, infection of the gastric mucosa caused by an autoimmune
reaction, and tumours.
There is insufficient data on the diagnostic reliability of the Helicobacter Test INFAI for
recommending its use in patients with gastrectomy.
-
In individual cases of A-gastritis (atrophic gastritis), the breath test can lead to false positive
results; other tests may therefore be necessary to confirm the presence of
Helicobacter pylori
.
-
If the patient vomits during the test procedure, necessitating the repetition of the test, this should
be done in fasted condition and not before the following day.
Taking other medicines
Helicobacter Test INFAI is influenced by all medicines related to
Helicobacter pylori
or urease
activity.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Pregnancy and breast-feeding
Ask your doctor or pharmacist for advice before taking any medicine.
It is not expected that performing the breath test during pregnancy and lactation has a damaging effect.
If you are a patient taking a medicine for eradication therapy it is recommended to check the patient
information leaflet of that drug with respect to the details on pregnancy and lactation.
Driving and using machines
Helicobacter Test INFAI has no influence on the ability to drive or to use machines.
3.
HOW TO TAKE HELICOBACTER TEST INFAI
Always take Helicobacter Test INFAI exactly as your doctor has told you. You should check with
your doctor or pharmacist if you are not sure.
You should perform the test in the presence of your doctor or another qualified person.
Dosage
The following information applies, unless your doctor has otherwise prescribed Helicobacter Test
INFAI. Please follow the instructions for use, as otherwise the Helicobacter Test INFAI may not work
properly.
37
How much Helicobacter Test INFAI should be used and how often?
Patients from the age of 12 must take the content of one jar with 75 mg for one test.
How and when should Helicobacter Test INFAI be used?
You must have fasted for 6 hours before application, preferably overnight. If fasting is a problem, for
example for diabetic patients, please tell your doctor.
The test procedure lasts approximately 40 minutes.
The test should be performed following at least four weeks without antibacterial therapy and two
weeks after the last administration of an antisecretory medication. Both of these substances could
influence the results of the Helicobacter Test INFAI. This is particularly true after Helicobacter
eradication therapy. It is important to follow the instructions for use exactly, otherwise the result may
be questionable.
Essential items not supplied with Helicobacter Test INFAI
Before the breath test is performed a liquid test meal is taken to delay stomach emptying. The test
meal is not provided with the kit. Pure orange juice (200 ml) or a solution of citric acid (1 g in 200 ml
of water) can be used as a test meal. If there is a medical (or other) reason why you cannot take either
of these test meals, please tell your doctor, who will suggest an alternative. A drinking vessel and tap
water is required to dissolve the
13
C-urea powder. If the test needs to be repeated, this should not be
done until the following day.
Special instructions for use (for mass spectrometry)
The test is to be performed after instruction by a healthcare professional and under appropriate medical
supervision. Each patient should be documented using the provided data sheet. It is recommended that
you take the test in a resting position.
1.
The test should be carried out after having fasted 6 hours before application, preferably
overnight. If the test needs to be carried out later in the day, only a light meal like tea and toast
is recommended.
2.
The test begins with the collection of samples for determining the baseline values:
•
The straw and sample tubes labelled “sampling time: 00-minute-value” are taken from the
test set.
•
The stopper is removed from one of the sample containers, the straw unwrapped and
placed into the container.
•
Now the patient breathes gently through the straw into the sample tube until the inside of
the sample tube steams up.
•
The patient must continue to breathe through the straw while removing it from the sample
tube, and then immediately seal the tube with its stopper. (If the sample tube remains
open for more than 30 seconds, the result could be falsified.)
•
The sample container should be held upright and the bar-code label marked 00-minute-
value will be stuck round the sample container so that the lines of the bar code are
horizontal.
3.
Now the second sample container (labelled “sampling time: 00-minute-value”) has to be filled
up with breath in the same way as described above.
4.
Then the patient must drink the recommended test meal (200 ml 100 % orange juice or 1 g citric
acid in 200 ml water).
5.
Now the preparation of the test solution follows.
•
The jar labelled “
13
C-urea powder” is removed from the test set, opened, and filled up to
about three quarters with tap water.
•
The jar is closed and carefully shaken until all the powder has dissolved completely.
•
The contents is poured into a drinking glass, the jar a second and third time filled with
water and the contents transferred into the drinking glass, so that approximately 30 ml of
test solution is obtained.
6.
The patient should drink this test solution immediately. The time of intake must be noted.
38
7.
30 minutes after the test solution has been taken (point 6), the “30-minute-value” samples are
collected in both containers, which remain in the pack (labelled “sampling time: 30-minute-
value”) as described under points 3 and 4.
The bar-code labels marked “30-minute-value” must be used for these samples.
8.
The corresponding bar-code label must be put on the data sheet for patient documentation. All
breath samples containers should be placed back into the original packaging. This packaging
should be sealed with the remaining sticker.
9.
The package must be sent to a qualified laboratory for analysis.
If you take more Helicobacter Test INFAI than you should
Because only 75 mg
13
C-urea is provided overdose is not to be expected.
4.
POSSIBLE SIDE EFFECTS
No side effects are known.
5.
HOW TO STORE HELICOBACTER TEST INFAI
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the label and carton.
Do not store above 25°C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Helicobacter Test INFAI contains
-
The active substance is
13
C-urea.
One jar contains 75 mg
13
C-urea.
-
There are no other ingredients.
What Helicobacter Test INFAI looks like and contents of the pack
Helicobacter Test INFAI is a clear, colourless powder for oral solution.
39
Content of the Test Kit:
No.
Component
Quantity
1
Jar (10 ml volume, polystyrene with polyethylene snap cap)
containing 75 mg
13
C-urea powder for oral solution
1
2
Labelled sample glass- or plastic- containers for sampling, storing
and transporting the breath samples for analysis:
Sampling time: 00-minute-value
Sampling time: 30-minute-value
2
2
3
Bendable straw for collection of the breath samples into the
corresponding sample containers
1
4
Data sheet for patient documentation
1
5
Package leaflet
1
6
Page of barcode labels and sticker
1
Marketing Authorisation Holder and Manufacturer
INFAI, Institut für Biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Germany
40
For any information about this medicinal product, please contact the local representative of the
Marketing Authorisation Holder.
België/Belgique/Belgien
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tél/Tel: +49 234 971130
Luxembourg/Luxemburg
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tél/Tel: +49 234 971130
България
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Teл.: +49 234 971130
Magyarország
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel.: +49 234 971130
Česká republika
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Malta
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Denmark
BioCare Nordic ApS
Langebjergvaenget 8A
DK-4000 Roskilde
Tlf: +45 4646 1191
Nederland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Deutschland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Norge
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tlf: +49 234 971130
Eesti
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Österreich
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Ελλ
ά
δα
Faran Laboratories s.a.
Αχαϊας και Τροιζηνίας
GR-14564 Νέα Κηφισιά
Τηλ: +30 210 626 9200
Polska
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel.: +49 234 971130
España
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Portugal
Goldfarma Lda
Rua Professor Francisco Gentil N
o
22-F
P-2620-097 Povoa de Santo Adrião
Tel: +351 219383280
41
France
Bioprojet Pharma
9, rue Rameau
F-75002 Paris
Tél: +33 1 470 366 33
România
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Ireland
INFAI UK Ltd.
York Science Park
(Innovation Centre)
University Road, Heslington
GB-York YO10 5DG
Tel: +44 1904 435 228
Slovenija
PLIVA Ljubljana d.o.o.
Pot k sejmišču 35
SI-1231 Ljubljana-Črnuče
Tel: +386 1 58 90 390
Ísland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Sími: +49 234 971130
Slovenská republika
ALLMEDICAL s.r.o.
Popradská 7
SK-040 01 Košice
Tel: +421 57 44 50030
Italia
INFAI Italia S.r.l.
via Borgogna 2
I-20112 Milano
Tel.: +39 0481 790350
Suomi/Finland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Puh/Tel: +49 234 971130
Κύπρος
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Τηλ: +49 234 971130
Sverige
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Latvija
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
United Kingdom
INFAI UK Ltd.
York Science Park
(Innovation Centre)
University Road, Heslington
GB-York YO10 5DG
Tel.: +44 1904 435 228
Lietuva
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
This leaflet was last approved in MM/YYYY
--------------------------------------------------------------------------------------------------------------------------------
The following information is intended for medical or healthcare professionals only:
Analysis of breath samples and testing specification for laboratories
The breath samples, collected in 10 l glass, plastic sample tubes are analysed by isotope ratio mass
spectrometry (IRMS).
42
The analysis of the
13
C/
12
C-ratio in carbon dioxide of breath is an integrated part of the diagnostic test
Helicobacter Test INFAI. The accuracy of the test strongly depends on the quality of the breath
analysis. The specification of breath analysis parameters like linearity, stability (reference gas
precision), and precision of measurement are fundamental for the accuracy of the system.
It has to be ensured that the analysis is carried out by a qualified laboratory. The method validated in
the application is as follows:
•
Sample preparation for (IRMS)
To determine the
13
C/
12
C-ratio of carbon dioxide in breath by mass spectrometric analysis the carbon
dioxide must be separated from the breath and introduced into the mass spectrometer. The automatic
preparation system for isotope mass spectrometers which is dedicated for breath test analysis is based
on a gas-chromatographic continuous flow separation technique.
Water is removed from the sample by means of a Nafion water trap or the gas-chromatographic
preparation system that separates the individual gases in a gas chromatographic column with Helium
as eluent. Passing the column the separated gas species of breath are detected by an ionisation
detector. The fraction of carbon dioxide gas, identified by its characteristic retention time, is
introduced into mass spectrometer.
•
Mass spectrometric analysis
To analyse the separated carbon dioxide sample gas its molecules must be ionised, formed into a
beam, accelerated by an electric field, deflected in a magnetic field, and finally detected. These five
processes take place in the analyser of a mass spectrometer, which consists of three separate sections:
the source, flight tube, and collector. Ionisation, beam formation and acceleration all occur in the
source, magnetic deflection takes place in the flight tube and detection takes place in the collector.
•
Sample inlet
For introduction of the carbon dioxide into the analyser many sample inlet systems are available. For
breath test analysis the individual balancing of the carbon dioxide of the sample to a reference
standard gas is essential. This ensures the high accuracy of this system, as calculation of the isotopic
content in carbon dioxide is done with respect to an independent standard.
•
Specifications for determining
13
C/
12
C-ratios
The breath test concept relies on the administration of a specifically
13
C-labelled urea whose
metabolite utilisation is monitored by measuring
13
CO
2
in the expired breath gas.
The mass spectrometer must be capable of:
Multiple replicate analyses:
Minimum of 3 replicate analyses on the same sample during operation
Security access:
Storing of operating parameters and of results under security access to
avoid later manipulation
Adjustment:
13
C/
12
C-ratio with respect to Pee Dee Beliminate (PDB)
Sample loop:
< 200 µl
The principal tests to verify the specifications are linearity, stability (reference gas precision), and
precision of measurement.
All mass spectrometers for breath analysis must comply with the following specifications:
43
Linearity:
≤ 0.5 ‰ for breath samples varying between 1 % and 7 %
CO
2
-concentration
Stability:
≤ 0.2 ‰ on 10 consecutive pulses
Precision of measurement: ≤ 0.3 ‰ for
13
C at natural abundance using a 10 ml breath sample
container with 3 % CO
2
breath concentration
Helicobacter pylori
infection is present if the difference in
13
C/
12
C of baseline-value and 30-minute-
value exceeds 4.0 ‰
.
Alternatively, any other suitable-validated method may be used, carried out by any objectively
qualified laboratory.
44
MINIMUM PARTICULARS TO APPEAR ON
DATA SHEET FOR PATIENT DOCUMENTATION
1.
Helicobacter Test INFAI
2.
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
3.
EXPIRY DATE
4.
BATCH NUMBER
5.
OTHER
Date of test
Patient´s full name
Date of birth
Barcode
Doctor/Hospital Address
45
PACKAGE LEAFLET: INFORMATION FOR THE USER
Helicobacter Test INFAI 75 mg powder for oral solution
13
C-urea
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for. Do not pass it on to others. It may harm them, even if
their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1.
What Helicobacter Test INFAI is and what it is used for
2.
Before you take Helicobacter Test INFAI
3.
How to take Helicobacter Test INFAI
5
How to store Helicobacter Test INFAI
6.
Further information
1.
WHAT HELICOBACTER TEST INFAI IS AND WHAT IT IS USED FOR
Helicobacter Test INFAI is for diagnostic use only.
Helicobacter Test INFAI is a breath test that can be used for adolescents from the age of 12 and older
and adults to determine whether or not you have an infection in the stomach caused by the bacterium
Helicobacter pylori
.
Why do you need to take the Helicobacter Test INFAI?
You may have a gastric infection caused by a bacterium called
Helicobacter pylori
. Your doctor has
recommended that you have a Helicobacter Test INFAI for one of the following reasons:
¾
Your doctor wants to confirm whether you are suffering from
Helicobacter pylori
infection to
help diagnose your condition.
¾
You have already been diagnosed has being infected with
Helicobacter pylori
and have been
taking medication aimed to clear up the infection. Your doctor now wishes to find out if the
treatment has been successful.
How does the test work?
All foods contain a substance called
13
Carbon (1 %
13
C). This
13
Carbon can be detected in the carbon
dioxide you breathe out of your lungs. The actual amount of
13
Carbon in the breath will depend on the
kind of food that you have eaten. You will be asked to drink the “test meal”. Following the meal,
samples of your breath will be taken (see “Special Instructions for use”).
These samples will be analysed to measure the “normal” amount of
13
Carbon content in the carbon
dioxide in your breath.
You will then be asked to drink a solution of
13
Carbon-urea.
Further samples of your breath will then be taken 30 minutes later and the amount of
13
Carbon in the
samples measured as before. The results will be compared and a significant increase in the amount of
13
Carbon in the second set of samples will suggest your doctor that
Helicobacter pylori
are present.
46
4.
Possible side effects
2.
BEFORE YOU TAKE HELICOBACTER TEST INFAI
Please tell your doctor if you suffer from any medical condition that you think may affect, or be
affected by the test. It is also important that you tell your doctor if any of the following circumstances
apply to you:
Do not take Helicobacter Test INFAI
-
if you have or if it is suspected that you have a gastric infection or an atrophic gastritis (special
form of gastritis), because this might interfere with the urea breath test.
Take special care with Helicobacter Test INFAI
Even if the result of Helicobacter Test INFAI is positive, further tests might be necessary before a
treatment of a
Helicobacter pylori
infection (eradication therapy) may be started. Various diagnostic
tests, including invasive endoscopic tests, could be required to check for the presence of any other
complications, such as gastric ulcer, infection of the gastric mucosa caused by an autoimmune
reaction, and tumours.
There is insufficient data on the diagnostic reliability of the Helicobacter Test INFAI for
recommending its use in patients with gastrectomy.
-
In individual cases of A-gastritis (atrophic gastritis), the breath test can lead to false positive
results; other tests may therefore be necessary to confirm the presence of
Helicobacter pylori
.
-
If the patient vomits during the test procedure, necessitating the repetition of the test, this should
be done in fasted condition and not before the following day.
Taking other medicines
Helicobacter Test INFAI is influenced by all medicines related to
Helicobacter pylori
or urease
activity.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Pregnancy and breast-feeding
Ask your doctor or pharmacist for advice before taking any medicine.
It is not expected that performing the breath test during pregnancy and lactation has a damaging effect.
If you are a patient taking a medicine for eradication therapy it is recommended to check the patient
information leaflet of that drug with respect to the details on pregnancy and lactation.
Driving and using machines
Helicobacter Test INFAI has no influence on the ability to drive or to use machines.
3.
HOW TO TAKE HELICOBACTER TEST INFAI
Always take Helicobacter Test INFAI exactly as your doctor has told you. You should check with
your doctor or pharmacist if you are not sure.
You should perform the test in the presence of your doctor or another qualified person.
Dosage
The following information applies, unless your doctor has otherwise prescribed Helicobacter Test
INFAI. Please follow the instructions for use, as otherwise the Helicobacter Test INFAI may not work
properly.
47
How much Helicobacter Test INFAI should be used and how often?
Patients from the age of 12 must take the content of one jar with 75 mg for one test.
How and when should Helicobacter Test INFAI be used?
You must have fasted for 6 hours before application, preferably overnight. If fasting is a problem, for
example for diabetic patients, please tell your doctor.
The test procedure lasts approximately 40 minutes.
The test should be performed following at least four weeks without antibacterial therapy and two
weeks after the last administration of an antisecretory medication. Both of these substances could
influence the results of the Helicobacter Test INFAI. This is particularly true after Helicobacter
eradication therapy. It is important to follow the instructions for use exactly, otherwise the result may
be questionable.
Essential items not supplied with Helicobacter Test INFAI
Before the breath test is performed a liquid test meal is taken to delay stomach emptying. The test
meal is not provided with the kit. Pure orange juice (200 ml) or a solution of citric acid (1 g in 200 ml
of water) can be used as a test meal. If there is a medical (or other) reason why you cannot take either
of these test meals, please tell your doctor, who will suggest an alternative. A drinking vessel and tap
water is required to dissolve the
13
C-urea powder. If the test needs to be repeated, this should not be
done until the following day.
Special Instructions for use (for infrared spectroscopy)
The test is to be performed after instruction by a healthcare professional and under appropriate medical
supervision. Each patient should be documented using the provided data sheet. It is recommended that
you take the test in a resting position.
1.
The test should be carried out after having fasted 6 hours before application, preferably
overnight. If the test needs to be carried out later in the day, only a light meal like tea and toast
is recommended.
2.
The test begins with the collection of samples for determining the baseline values:
•
The straw and one breath bag labelled “sampling time: 00-minute-value” are taken from
the test set.
•
The stopper is removed from one of the breath bags, the straw unwrapped and placed into
the container.
•
Now the patient breathes gently through the straw into the breath bag.
•
The patient must continue to breathe through the straw while removing it from the breath
bag, and then immediately seal the breath bag with its stopper. (If the breath bag remains
open for more than 30 seconds, the test result might be falsified.)
•
The breath bag should be held upright and the bar-code label marked 00-minute-value
will be stuck on the breath bag.
3.
Then the patient must drink the recommended test meal (200 ml 100 % orange juice or 1 g citric
acid in 200 ml water).
4.
Now the preparation of the test solution follows.
•
The jar labelled “
13
C-urea powder” is removed from the test set, opened, and filled up to
about three quarters with tap water.
•
The jar is closed and carefully shaken until all the powder has dissolved completely.
•
The contents is poured into a drinking glass, the jar a second and third time filled with
water and the contents transferred into the drinking glass, so that approximately 30 ml of
test solution is obtained.
5.
The patient should drink this test solution immediately. The time of intake must be noted.
6.
30 minutes after the test solution has been taken (point 5), the “30-minute-value” samples are
collected in one breath bag, which remains in the pack (labelled “sampling time: 30-minute-
value”) as described above.
The bar-code labels marked “30-minute-value” must be used for these samples.
48
7.
The corresponding bar-code label must be put on the data sheet for patient documentation. All
breath bags should be placed back into the original packaging. This packaging should be sealed
with the remaining sticker.
8.
The package must be sent to a qualified laboratory for analysis.
If you take more Helicobacter Test INFAI than you should
Because only 75 mg
13
C-urea is provided overdose is not to be expected.
4.
POSSIBLE SIDE EFFECTS
No side effects are known.
5.
HOW TO STORE HELICOBACTER TEST INFAI
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the label and carton.
Do not store above 25°C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6. FURTHER INFORMATION
What Helicobacter Test INFAI contains
-
The active substance is
13
C-urea.
One jar contains 75 mg
13
C-urea.
-
There are no other ingredients.
What Helicobacter Test INFAI looks like and contents of the pack
Helicobacter Test INFAI is a clear, colourless powder for oral solution.
Content of the Test Kit with 1 jar:
No.
Component
Quantity
1
Jar (10 ml volume, polystyrene with polyethylene snap cap)
containing 75 mg
13
C-urea powder for oral solution
1
2
Labelled sample breath bags for sampling, storing and transporting
the breath samples for analysis:
breath bags:
Sampling time: 00-minute-value
Sampling time: 30-minute-value
1
1
Bendable straw for collection of the breath samples into the
corresponding sample tubes
3
1
4
Data sheet for patient documentation
1
5
Package leaflet
1
6
Page of barcode labels and sticker
1
49
Content of the Test Kit with 50 jars:
No.
Component
Quantity
Jar (10 ml volume, polystyrene with polyethylene snap cap)
containing 75 mg
13
C-urea powder for oral solution
1
50
2
Breath bags:
Sampling time: 00-minute-value
Sampling time: 30-minute-value
50
50
Bendable straw for collection of the breath samples into the
corresponding sample containers
3
50
4
Data sheet for patient documentation
50
5
Package leaflet
50
6
Page of barcode labels and sticker
50
Marketing Authorisation Holder and Manufacturer
INFAI, Institut für Biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Germany
50
For any information about this medicinal product, please contact the local representative of the
Marketing Authorisation Holder.
België/Belgique/Belgien
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tél/Tel: +49 234 971130
Luxembourg/Luxemburg
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tél/Tel: +49 234 971130
България
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Teл.: +49 234 971130
Magyarország
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel.: +49 234 971130
Česká republika
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Malta
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Denmark
BioCare Nordic ApS
Langebjergvaenget 8A
DK-4000 Roskilde
Tlf: +45 4646 1191
Nederland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Deutschland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Norge
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tlf: +49 234 971130
Eesti
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Österreich
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Ελλ
ά
δα
Faran Laboratories s.a.
Αχαϊας και Τροιζηνίας
GR-14564 Νέα Κηφισιά
Τηλ: +30 210 626 9200
Polska
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel.: +49 234 971130
España
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Portugal
Goldfarma Lda
Rua Professor Francisco Gentil N
o
22-F
P-2620-097 Povoa de Santo Adrião
Tel: +351 219383280
51
France
Bioprojet Pharma
9, rue Rameau
F-75002 Paris
Tél: +33 1 470 366 33
România
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Ireland
INFAI UK Ltd.
York Science Park
(Innovation Centre)
University Road, Heslington
GB-York YO10 5DG
Tel: +44 1904 435 228
Slovenija
PLIVA Ljubljana d.o.o.
Pot k sejmišču 35
SI-1231 Ljubljana-Črnuče
Tel: +386 1 58 90 390
Ísland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Sími: +49 234 971130
Slovenská republika
ALLMEDICAL s.r.o.
Popradská 7
SK-040 01 Košice
Tel: +421 57 44 50030
Italia
INFAI Italia S.r.l.
via Borgogna 2
I-20112 Milano
Tel.: +39 0481 790350
Suomi/Finland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Puh/Tel: +49 234 971130
Κύπρος
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Τηλ: +49 234 971130
Sverige
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Latvija
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
United Kingdom
INFAI UK Ltd.
York Science Park
(Innovation Centre)
University Road, Heslington
GB-York YO10 5DG
Tel.: +44 1904 435 228
Lietuva
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
This leaflet was last approved in MM/YYYY
--------------------------------------------------------------------------------------------------------------------------------
The following information is intended for medical or healthcare professionals only:
Analysis of breath samples and testing specification for laboratories
The breath samples, collected in breath bags are analysed by non-dispersive infrared spectroscopy
(NDIR).
52
The analysis of the
13
C/
12
C-ratio in carbon dioxide of breath is an integrated part of the diagnostic test
Helicobacter Test INFAI. The accuracy of the test strongly depends on the quality of the breath
analysis. The specification of breath analysis parameters like linearity, stability (reference gas
precision), and precision of measurement are fundamental for the accuracy of the system.
It has to be ensured that the analysis is carried out by a qualified laboratory. It is recommended to
measure as soon as possible after the breath collection, in any case not later than 4 weeks.
The method validated in the application is as follows:
•
Sample preparation for Infrared Spectroscopy (NDIR)
The determination of
13
C/
12
C-ratio in the carbon dioxide of the breath samples is carried out directly in
the breath. The breath from the bags will be introduced into the NDIR spectrometer using a variable
gas pump. The water content of the breath sample will be kept mostly constant through Nafion water
trap. For calibration and measurement necessary CO
2
-free air (zero-gas) will be produced via an
integrated CO
2
-absorber in the analysator.
•
Infrared spectroscopic analysis
To analyse the carbon dioxide in breath a broad band infrared radiation bunch emitted by an infrared
radiation source is alternately sent through the measuring chamber and a reference chamber by means
of a beam chopper. The modulated infrared beams then enter the infrared detectors, which are double
layer transmission detectors with a front, and a rear chamber each filled with one of the isotopicly pure
gases (
13
CO
2
or
12
CO
2
, respectively) to be measured. The infrared radiation in the measuring chamber
is weakened by the gas component to be measured. Thus the radiation equilibrium between measuring
and comparative beam is disturbed. In consequence there is a temperature fluctuation, which in its turn
causes a fluctuating pressure in the front chamber of the infrared detector. A membrane capacitor
connected with this chamber, which is exposed to a high resistance direct voltage, transforms these
pressure fluctuations into an alternating voltage, which is a measure of the isotopic composition of
breath carbon dioxide.
•
Sample Inlet
A semi-automatic sample inlet system injects the measuring gas in definite amounts into the zero gas
circulating in the gas circuit of the infrared spectrometer. This enables measurement of the
13
C/
12
C
ratio at any CO
2
concentration above 1%.
•
Specifications for determining
13
C/
12
C-ratios
The breath test concept is based upon the oral administration of
13
C-labelled urea whose enzymatic
hydrolysis is monitored by measuring
13
CO
2
in breath using non-dispersive infrared spectrometry.
Infrared spectrometers for breath analysis must comply with the following specifications:
Multiple replicate analyses: Minimum of 3 replicate analyses of one and the same sample during
operation
Security access:
Storing of operating parameters and results under security access to
avoid later manipulation
For verifying the specifications linearity, stability, and precision of measurement have to be tested.
Zero point adjustment of the detectors by means of the zero gas generated in the spectrometer. End-
point adjustment of the detectors by means of calibration gases of precisely known concentration.
53
Linearity:
≤ 0.5 ‰ for breath samples varying between 1 % and 7 % CO
2
-
concentration
Stability:
≤ 0.3‰ at 10 consecutive pulses
Precision of measurement: ≤ 0.5 ‰ for
13
C at natural abundance using a 100 ml breath bag with
3 % CO
2
breath concentration
Helicobacter pylori
infection is present if the difference in
13
C/
12
C of baseline-value and 30-minute-
value exceeds 4.0 ‰
.
Alternatively, any other suitably validated method may be used, carried out by any objectively
qualified laboratory.
54
MINIMUM PARTICULARS TO APPEAR ON
DATA SHEET FOR PATIENT DOCUMENTATION
1.
Helicobacter Test INFAI
2.
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
3.
EXPIRY DATE
4.
BATCH NUMBER
5.
OTHER
Date of test
Patient´s full name
Date of birth
Barcode
Doctor/Hospital Address
55
PACKAGE LEAFLET: INFORMATION FOR THE USER
Helicobacter Test INFAI for children of the age 3-11 45 mg powder for oral solution
13
C-urea
Read all of this leaflet carefully before you start taking this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
if their symptoms are the same as yours.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
:
1.
What Helicobacter Test INFAI for children of the age 3-11 years is and what it is used for
2.
Before you take Helicobacter Test INFAI for children of the age 3-11
3.
How to take Helicobacter Test INFAI for children of the age 3-11
5
How to store Helicobacter Test INFAI for children of the age 3-11
6.
Further information
1.
WHAT HELICOBACTER TEST INFAI FOR CHILDREN AGED 3 TO 11 YEARS IS
AND WHAT IT IS USED FOR
Helicobacter Test INFAI for children of the age 3-11 is for diagnostic use only.
Helicobacter Test INFAI for children aged 3-11 years is a breath test, which can be used to determine
if there is an infection in the stomach or duodenum caused by the bacteria
Helicobacter pylori
.
Why do you need to take the Helicobacter Test INFAI for children of the age 3-11?
You may have a gastric infection caused by a bacterium called
Helicobacter pylori
. Your doctor has
recommended that you have a Helicobacter Test INFAI for children of the age 3-11 for one of the
following reasons:
¾
Your doctor wants to confirm whether you are suffering from
Helicobacter pylori
infection to
help diagnose your condition.
¾
You have already been diagnosed has being infected with
Helicobacter pylori
and have been
taking medication aimed to clear up the infection. Your doctor now wishes to find out if the
treatment has been successful.
How does the test work?
All foods contain a substance called
13
Carbon (1 %
13
C). This
13
Carbon can be detected in the carbon
dioxide you breathe out of your lungs. The actual amount of
13
Carbon in the breath will depend on the
kind of food that you have eaten. You will be asked to drink the “test meal”. Following the meal,
samples of your breath will be taken (see “Special Instructions for use”).
These samples will be analysed to measure the “normal” amount of
13
Carbon content in the carbon
dioxide in your breath.
You will then be asked to drink a solution of
13
Carbon-urea.
Further samples of your breath will then be taken 30 minutes later and the amount of
13
Carbon in the
samples measured as before. The results will be compared and a significant increase in the amount of
13
Carbon in the second set of samples will suggest your doctor that
Helicobacter pylori
are present.
56
4.
Possible side effects
2.
BEFORE YOU TAKE HELICOBACTER TEST INFAI FOR CHILDREN OF THE AGE
3-11
Please tell your doctor if you suffer from any medical condition that you think may affect, or be
affected by the test. It is also important that you tell your doctor if any of the following circumstances
apply to you:
Do not take Helicobacter Test INFAI for children of the age 3-11
- if you have or if it is suspected that you have a gastric infection or an atrophic gastritis (special
form of gastritits), because this might interfere with the urea breath test.
Take special care with Helicobacter Test INFAI for children of the age 3-11
Even if the result of Helicobacter Test INFAI is positive, further tests might be necessary before a
treatment of a
Helicobacter pylori
infection (eradication therapy) may be started. Various diagnostic
tests, including invasive endoscopic tests, could be required to check for the presence of any other
complications, such as gastric ulcer, infection of the gastric mucosa caused by an autoimmune
reaction, and tumours.
There is insufficient data on the diagnostic reliability of the Helicobacter Test INFAI for children of
the age 3-11 for recommending its use in patients with gastrectomy.
-
In individual cases of A-gastritis (atrophic gastritis), the breath test can lead to false positive
results; other tests may therefore be necessary to confirm the presence of
Helicobacter pylori
.
-
If the patient vomits during the test procedure, necessitating the repetition of the test, this should
be done in fasted condition and not before the following day.
Taking other medicines
Helicobacter Test INFAI for children of the age 3-11 is influenced by all medicines related to
Helicobacter pylori
or urease activity.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
3.
HOW TO TAKE HELICOBACTER TEST INFAI FOR CHILDREN OF THE AGE 3-11
Always take Helicobacter Test INFAI for children of the age 3-11 exactly as your doctor has told you.
You should check with your doctor or pharmacist if you are not sure.
You should perform the test in the presence of your doctor or another qualified person.
Dosage
The following information applies, unless your doctor has otherwise prescribed Helicobacter Test
INFAI for children of the age 3-11. Please follow the instructions for use, as otherwise the
Helicobacter Test INFAI for children of the age 3-11 years may not work properly.
How much Helicobacter Test INFAI for children of the age 3-11 should be used and how often?
Patients from the age of 3-11 must take the content of one jar with 45 mg for one test.
How and when should Helicobacter Test INFAI for children of the age 3-11 be used?
You must have fasted for 6 hours before application, preferably overnight. If fasting is a problem, for
example for diabetic patients, please tell your doctor.
The test procedure lasts approximately 40 minutes.
57
The test should be performed following at least four weeks without antibacterial therapy and two
weeks after the last administration of an antisecretory medication. Both of these substances could
influence the results of the Helicobacter Test INFAI for children of the age 3-11. This is particularly
true after Helicobacter eradication therapy. It is important to follow the instructions for use exactly,
otherwise the result may be questionable.
Essential items not supplied with Helicobacter Test INFAI for children of the age 3-11
Before the breath test is performed a liquid test meal is taken to delay stomach emptying. The test
meal is not provided with the kit. Pure orange juice (100 ml) can be used as a test meal. If there is a
medical (or other) reason why you cannot take either of these test meals, please tell your doctor, who
will suggest an alternative. A drinking vessel and tap water is required to dissolve the
13
C-urea
powder. If the test needs to be repeated, this should not be done until the following day.
Special Instructions for use (for mass spectrometry)
The test is to be performed after instruction by a healthcare professional and under appropriate medical
supervision. Each patient should be documented using the provided data sheet. It is recommended that
you take the test in a resting position.
1.
The test should be carried out after having fasted 6 hours before application, preferably
overnight. If the test needs to be carried out later in the day, only a light meal like tea and toast
is recommended.
2.
The test begins with the collection of samples for determining the baseline values:
•
The straw and sample tubes labelled “sampling time: 00-minute-value” are taken from the
test set.
•
The stopper is removed from one of the sample containers, the straw unwrapped and
placed into the container.
•
Now the patient breathes gently through the straw into the sample tube until the inside of
the sample tube steams up.
•
The patient must continue to breathe through the straw while removing it from the sample
tube and then immediately seal the tube with its stopper. (If the sample tube remains open
for more than 30 seconds, the test result might be falsified.)
•
The sample container should be held upright and the bar-code label marked 00-minute-
value will be stuck round the sample container so that the lines of bar code are horizontal.
3.
Now the second sample container (labelled “sampling time: 00-minute-value”) has to be filled
up with breath in the same way as described above.
4.
Then the patient must drink the recommended test meal (100 ml 100 % orange juice).
5.
Now the preparation of the test solution follows.
•
The jar labelled “
13
C-urea powder” is removed from the test set, opened, and filled up to
about three quarters with tap water.
•
The jar is closed and carefully shaken until all the powder has dissolved completely.
•
The contents is poured into a drinking glass, the jar a second and third time filled with
water and the contents transferred into the drinking glass, so that approximately 30 ml of
test solution is obtained.
6. The patient should drink this test solution immediately. The time of intake must be noted.
7. 30 minutes after the test solution has been taken (point 6), the “30-minute-value” samples are
collected in both containers, which remains in the pack (labelled “sampling time: 30-minute-
value”) as described above.
The bar-code labels marked “30-minute-value” must be used for these samples.
8.
The corresponding bar-code label must be put on the data sheet for patient documentation. All
breath samples containers should be placed back into the original packaging. This packaging
should be sealed with the remaining sticker.
9.
The package must be sent to a qualified laboratory for analysis.
If you take more Helicobacter Test INFAI for children of the age 3-11 than you should
Because only 45 mg
13
C-urea is provided overdose is not to be expected.
58
4.
POSSIBLE SIDE EFFECTS
No side effects are known.
5.
HOW TO STORE HELICOBACTER TEST INFAI FOR CHILDREN OF THE AGE 3-11
Keep out of the reach and sight of children.
Do not use after the expiry date which is stated on the label and carton.
Do not store above 25°C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help to protect the environment.
6.
FURTHER INFORMATION
What Helicobacter Test INFAI for children of the age 3-11contains
-
The active substance is
13
C-urea.
One jar contains 45 mg
13
C-urea.
-
There are no other ingredients.
What Helicobacter Test INFAI for children of the age 3-11 looks like and contents of the pack
Helicobacter Test INFAI for children of the age 3-11 years is a clear, colourless powder for oral
solution.
Content of the Test Kit:
No.
Component
Quantity
1
Jar (10 ml volume, polystyrene with polyethylene snap cap)
containing 45 mg
13
C-urea powder for oral solution
1
2
Labelled sample glass- or plastic containers for sampling, storing
and transporting the breath samples for analysis:
Sampling time: 00-minute-value
Sampling time: 30-minute-value
2
2
3
Bendable straw for collection of the breath samples into the
corresponding sample tubes
1
4
Data sheet for patient documentation
1
5
Package leaflet
1
6
Page of barcode labels and sticker
1
Marketing Authorisation Holder and Manufacturer
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Germany
59
For any information about this medicinal product, please contact the local representative of the
Marketing Authorisation Holder.
België/Belgique/Belgien
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tél/Tel: +49 234 971130
Luxembourg/Luxemburg
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tél/Tel: +49 234 971130
България
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Teл.: +49 234 971130
Magyarország
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel.: +49 234 971130
Česká republika
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Malta
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Denmark
BioCare Nordic ApS
Langebjergvaenget 8A
DK-4000 Roskilde
Tlf: +45 4646 1191
Nederland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Deutschland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Norge
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tlf: +49 234 971130
Eesti
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Österreich
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Ελλ
ά
δα
Faran Laboratories s.a.
Αχαϊας και Τροιζηνίας
GR-14564 Νέα Κηφισιά
Τηλ: +30 210 626 9200
Polska
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel.: +49 234 971130
España
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Portugal
Goldfarma Lda
Rua Professor Francisco Gentil N
o
22-F
P-2620-097 Povoa de Santo Adrião
Tel: +351 219383280
60
France
Bioprojet Pharma
9, rue Rameau
F-75002 Paris
Tél: +33 1 470 366 33
România
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Ireland
INFAI UK Ltd.
York Science Park
(Innovation Centre)
University Road, Heslington
GB-York YO10 5DG
Tel: +44 1904 435 228
Slovenija
PLIVA Ljubljana d.o.o.
Pot k sejmišču 35
SI-1231 Ljubljana-Črnuče
Tel: +386 1 58 90 390
Ísland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Sími: +49 234 971130
Slovenská republika
ALLMEDICAL s.r.o.
Popradská 7
SK-040 01 Košice
Tel: +421 57 44 50030
Italia
INFAI Italia S.r.l.
via Borgogna 2
I-20112 Milano
Tel.: +39 0481 790350
Suomi/Finland
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Puh/Tel: +49 234 971130
Κύπρος
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Τηλ: +49 234 971130
Sverige
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
Latvija
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
United Kingdom
INFAI UK Ltd.
York Science Park
(Innovation Centre)
University Road, Heslington
GB-York YO10 5DG
Tel.: +44 1904 435 228
Lietuva
INFAI, Institut für biomedizinische Analytik und
NMR-Imaging GmbH
Universitätsstraße 142
D-44799 Bochum
Tel: +49 234 971130
This leaflet was last approved in MM/YYYY
--------------------------------------------------------------------------------------------------------------------------------
The following information is intended for medical or healthcare professionals only:
Analysis of breath samples and testing specification for laboratories
The breath samples, collected in 10 ml glass- or plastic sample tubes, are analysed by isotope ratio
mass spectrometry (IRMS).
61
The analysis of the
13
C/
12
C-ratio in carbon dioxide of breath is an integrated part of the diagnostic test
Helicobacter Test INFAI. The accuracy of the test strongly depends on the quality of the breath
analysis. The specification of breath analysis parameters like linearity, stability (reference gas
precision), and precision of measurement are fundamental for the accuracy of the system.
It has to be ensured that the analysis is carried out by a qualified laboratory. The method validated in
the application is as follows:
•
Sample preparation for (IRMS)
To determine the
13
C/
12
C-ratio of carbon dioxide in breath by mass spectrometric analysis the carbon
dioxide must be separated from the breath and introduced into the mass spectrometer. The automatic
preparation system for isotope mass spectrometers which is dedicated for breath test analysis is based
on a gas-chromatographic continuous flow separation technique.
Water is removed from the sample by means of a Nafion water trap or the gas-chromatographic
preparation system that separates the individual gases in a gas chromatographic column with Helium
as eluent. Passing the column the separated gas species of breath are detected by an ionisation
detector. The fraction of carbon dioxide gas, identified by its characteristic retention time, is
introduced into mass spectrometer.
•
Mass spectrometric analysis
To analyse the separated carbon dioxide sample gas its molecules must be ionised, formed into a
beam, accelerated by an electric field, deflected in a magnetic field, and finally detected. These five
processes take place in the analyser of a mass spectrometer, which consists of three separate sections:
the source, flight tube, and collector. Ionisation, beam formation and acceleration all occur in the
source, magnetic deflection takes place in the flight tube and detection takes place in the collector.
•
Sample inlet
For introduction of the carbon dioxide into the analyser many sample inlet systems are available. For
breath test analysis the individual balancing of the carbon dioxide of the sample to a reference
standard gas is essential. This ensures the high accuracy of this system, as calculation of the isotopic
content in carbon dioxide is done with respect to an independent standard.
•
Specifications for determining
13
C/
12
C-ratios
The breath test concept relies on the administration of a specifically
13
C-labelled urea whose
metabolite utilisation is monitored by measuring
13
CO
2
in the expired breath gas.
The mass spectrometer must be capable of:
Multiple replicate analyses: Minimum of 3 replicate analyses on the same sample during operation
Security access:
Storing of operating parameters and of results under security access to
avoid later manipulation
Adjustment:
13
C/
12
C-ratio with respect to Pee Dee Beliminate (PDB)
Sample loop:
< 200 µl
The principle tests to verify the specifications are linearity, stability (reference gas precision), and
precision of measurement.
All mass spectrometers for breath analysis must comply with the following specifications:
62
Linearity:
≤ 0.5 ‰ for breath samples varying between 1 % and 7 % CO
2
-
concentration
Stability:
≤ 0.2 ‰ on 10 consecutive pulses
Precision of measurement: ≤ 0.3 ‰ for
13
C at natural abundance using a 10ml breath sample tube
with 3 % CO
2
breath concentration
Helicobacter pylori
infection is present if the difference in
13
C/
12
C of baseline-value and 30-minute-
value exceeds 4.0 ‰.
Alternatively, any other suitable-validated method may be used, carried out by any objectively
qualified laboratory.
63
MINIMUM PARTICULARS TO APPEAR ON
DATA SHEET FOR PATIENT DOCUMENTATION
1.
Helicobacter Test INFAI
2.
INFAI, Institut für biomedizinische Analytik und NMR-Imaging GmbH
Universitätsstr. 142
D-44799 Bochum
Germany
3.
EXPIRY DATE
4.
BATCH NUMBER
5.
OTHER
Date of test
Patient´s full name
Date of birth
Barcode
Doctor/Hospital Address
64
Source: European Medicines Agency
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