ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
Suspension for injection
Pandemic influenza vaccine (whole virion, Vero cell derived, inactivated)
Whole virion influenza vaccine, inactivated containing antigen of pandemic strain*:
A/Vietnam/1203/2004 (H5N1)
7.5 micrograms**
per 0.5 ml dose
* propagated in Vero cells (continuous cell line of mammalian origin)
** expressed in micrograms haemagglutinin.
This vaccine complies with the WHO recommendation and EU decision for the pandemic.
This is a multidose container. See section 6.5 for the number of doses per vial.
For a full list of excipients, see section 6.1.
3.
Suspension for injection.
The vaccine is an off-white, opalescent, translucent suspension.
4.
Prophylaxis of influenza in an officially declared pandemic situation. Pandemic influenza vaccine
should be used in accordance with official guidance.
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER has been evaluated in adults 18-59 years of
age and in elderly 60 years of age and above.
Adults: first dose of 0.5 ml at an elected date.
A second dose of vaccine should be given after an interval of at least 3 weeks.
There is no data on PANDEMIC INFLUENZA VACCINE H5N1 BAXTER vaccination dose and
schedule for subjects under 18 years old and for subjects with co-morbidities (e.g. immunosuppressed
subjects). In a pandemic situation administration of the vaccine in those populations shall follow
national recommendations.
For further information, see section 5.1.
Immunization should be carried out by intramuscular injection into the deltoid muscle.
2
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues
(e.g. formaldehyde, benzonase, sucrose) of this vaccine. However, in a pandemic situation, it may be
appropriate to give the vaccine, provided that facilities for resuscitation are immediately available in
case of need.
See section 4.4.
Caution is needed when administrating this vaccine to persons with a known hypersensitivity (other
than anaphylactic reaction) to the active substance(s), to any of the excipients and to trace residues e.g.
formaldehyde, benzonase, or sucrose.
As with all injectable vaccines, appropriate medical treatment and supervision should always be
readily available in case of a rare anaphylactic event following the administration of the vaccine.
If the pandemic situation allows, immunisation shall be postponed in patients with severe febrile
illness or acute infection.
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER should under no circumstances be
administered intravascularly.
There are no data with PANDEMIC INFLUENZA VACCINE H5N1 BAXTER using the
subcutaneous route. Therefore, healthcare providers need to assess the benefits and potential risks of
administering the vaccine in individuals with thrombocytopenia or any bleeding disorder that would
contraindicate intramuscular injection unless the potential benefit outweighs the risk of bleedings.
Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient.
A protective response may not be induced in all vaccinees (see section 5.1).
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER should not be given at the same time as other
vaccines. However, if co-administration with another vaccine is indicated, immunisation should be
carried out on separate limbs. It should be noted that the adverse reactions may be intensified.
Immunoglobulin is not to be given with PANDEMIC INFLUENZA VACCINE H5N1 BAXTER. If it
is necessary to provide immediate protection, PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
may be given at the same time as normal or specific immunoglobulin. Injections of PANDEMIC
INFLUENZA VACCINE H5N1 BAXTER and immunoglobulin should be made into separate limbs.
The immunological response may be diminished if the patient is undergoing immunosuppressant
treatment.
Following influenza vaccination, false positive results in serology tests using the ELISA method to
detect antibodies against HIV1, Hepatitis C and especially HTLV1 have been observed. The Western
Blot technique disproves the results. The transient false positive reactions could be due to the IgM
response by the vaccine.
3
4.6
Data from vaccinations with interpandemic trivalent vaccines in pregnant women do not indicate that
adverse foetal and maternal outcomes were attributable to the vaccine. Therefore, for pregnant women,
administration of the pandemic influenza vaccine is recommended, irrespective of their stage of
pregnancy.
The vaccine PANDEMIC INFLUENZA VACCINE H5N1 BAXTER may be used during lactation.
Some undesirable effects mentioned under section 4.8 such as dizziness and vertigo may affect the
ability to drive or use machines.
In clinical trials with the mock-up vaccine (see section 5.1) in 606 subjects (326 between 18 and 59
years old, and 280 aged 60 and above), the following adverse reactions were assessed as at least
possibly related by the investigator. Most of the reactions were mild in nature, of short duration and
qualitatively similar to those induced by influenza vaccines. There were fewer reactions after the
second dose of the vaccine compared with the first dose. The most frequently occurring adverse
reaction was injection site pain, which was usually mild.
Adverse reactions are listed according to the following frequency. Within each frequency grouping,
adverse reactions are presented in the order of decreasing seriousness.
Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000).
Not known (cannot be estimated from the available data)
Infections and infestations
Common: nasopharyngitis
Blood and the lymphatic system disorders
Uncommon: lymphadenopathy
Psychiatric disorders
Uncommon: insomnia, restlessness
Nervous system disorders
Common: headache, dizziness
Uncommon: somnolence, dysaesthesia,
Eye disorders
Uncommon: conjunctivitis
Ear and labyrinth disorders
Common: vertigo
Uncommon: sudden hearing loss
4
Vascular disorders
Uncommon: hypotension
Respiratory, thoracic and mediastinal disorders
Common: pharyngolaryngeal pain
Uncommon: dyspnoea, cough, rhinorrhoea, nasal congestion
Gastrointestinal disorders
Uncommon: gastro-intestinal symptoms (such as nausea, vomiting, diarrhoea and upper abdominal
pain)
Skin and subcutaneous tissue disorders
Common: hyperhidrosis
Uncommon: rash, pruritus
Musculoskeletal and connective tissue disorders
Common: arthralgia, myalgia
General disorders and administration site conditions
Very common: injection site pain
Common: pyrexia, chills, fatigue, malaise, induration, erythema, swelling and haemorrhage at the
injection site
Uncommon: injection site irritation
Post-marketing surveillance
For cell-based influenza vaccines, post-marketing surveillance data are not yet available. From post-
marketing surveillance with egg-derived interpandemic trivalent vaccines, the following serious
adverse reactions have been reported:
Uncommon:
Generalised skin reactions including pruritus, urticaria, and non-specific rash.
Rare
:
Neuralgia, paraesthesia, convulsions, transient thrombocytopenia.
Allergic reactions, in rare cases leading to shock, have been reported.
Very rare
:
Vasculitis with transient renal involvement.
Neurological disorders, such as encephalomyelitis, neuritis and Guillain Barré syndrome.
No case of overdose has been reported.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Influenza vaccines, ATC Code J07BB01
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER has been authorised under “exceptional
circumstances”. This means that for scientific reasons, it has not been possible to obtain complete
information on this medicinal product. The European Medicines Agency (EMEA) will review any new
information which may become available every year and this SPC will be updated as necessary.
5
This section describes the clinical experience with the mock-up vaccine following a two-dose
administration.
Mock-up vaccines contain influenza antigens that are different from those in the currently circulating
influenza viruses. These antigens can be considered as ‘novel’ antigens and simulate a situation where
the target population for vaccination is immunologically naïve. Data obtained with the mock-up
vaccine will support a vaccination strategy that is likely to be used for the pandemic vaccine: clinical
immunogenicity, safety and reactogenicity data obtained with mock-up vaccines are relevant for the
pandemic vaccines.
Immune response against the vaccine strain contained in PANDEMIC INFLUENZA VACCINE
H5N1 BAXTER (A/Vietnam/1203/2004)
The immunogenicity of the 7.5 µg non-adjuvanted formulation of PANDEMIC INFLUENZA
VACCINE H5N1 BAXTER (strain A/Vietnam/1203/2004) has been evaluated in two clinical studies
in adults aged 18 – 59 years (N=312) and in elderly subjects aged 60 years and older (N=272)
following a 0, 21 day schedule.
After primary vaccination the seroprotection rate, seroconversion rate and seroconversion factor for
anti-HA antibody as measured by single radial haemolysis (SRH) in adults aged 18 to 59 years and in
elderly subjects aged 60 years and above were as follows:
SRH Assay
18 – 59 years
60 years and above
21 Days After
21 Days After
1
st
Dose
2
nd
Dose
1
st
Dose
2
nd
Dose
Seroprotection rate*
55.5%
65.4%
57.9%
67.7%
Seroconversion rate**
51.3%
62.1%
52.4%
62.4%
Seroconversion
factor***
3.7
4.8
3.6
4.6
*
SRH area
>
25 mm²
**
either SRH area ≥ 25 mm
2
if baseline sample negative or 50% increase in SRH area if baseline sample
>4 mm²
***
geometric mean increase
After primary vaccination the rate of subjects with neutralizing antibody titres
>
20, seroconversion
rate and seroconversion factor as measured by microneutralisation assay (MN) in adults aged 18 to 59
years and in elderly subjects aged 60 years and above were as follows:
Microneutralisation
assay
18 – 59 years
60 years and above
21 Days After
21 Days After
1
st
Dose
2
nd
Dose
1
st
Dose
2
nd
Dose
Seroneutralisation
rate*
49.4%
73.0%
54.4%
74.1%
Seroconversion rate**
39.1%
61.9%
14.3%
26.7%
Seroconversion
factor***
3.4
4.7
2.1
2.8
*
MN titre
>
20
**
>
4-fold increase in MN titre
***
geometric mean increase
6
Cross-reactive Immune Response Against Related H5N1 Strains
In the phase 3 study in adults (N=265) and elderly subjects (N=270) after vaccination with the
A/Vietnam/1203/2004 strain vaccine the rate of subjects with cross-neutralising antibodies as
measured by MN (titre
>
20) was as follows:
18 – 59 years
60 years and above
Day 42
a
Day 180
Day 42
a
Day 180
Tested against
Strain A/Indonesia/05/2005
Seroneutralisation rate*
35.1%
14.4%
54.8%
28.0%
*
21 days after 2
nd
dose
In a dose-finding study in adults aged 18 – 45 years investigating various dose levels of adjuvanted
and non-adjuvanted formulations of the A/Vietnam/1203/2004 strain vaccine the rates of subjects with
neutralising antibody titres
>
20, seroconversion rates and seroconversion factor for cross-neutralising
antibodies as measured by MN in subjects who received the 7.5 µg non-adjuvanted formulation
(N=42) were as follows:
Tested against
Strain A/Indonesia/05/2005
Day 42
a
Day 180
Seroneutralisation rate*
45.2%
33.3%
Seroconversion rate**
31.0%
21.4%
Seroconversion
factor***
3.2
2.5
*
MN titre
>
20
**
>
4-fold increase in MN titre
***
geometric mean increase
a
21 days after 2
nd
dose
Antibody Persistence and Booster Vaccination with Homologous and Heterologous Vaccine Strains
Antibody persistence after vaccination with the 7.5 µg non-adjuvanted formulation of PANDEMIC
INFLUENZA VACCINE H5N1 BAXTER (strain A/Vietnam/1203/2004) has been evaluated in two
clinical studies in adults aged 18 – 59 years (N=285) and in one clinical study in elderly subjects aged
60 years and above (N=258) up to 6 months after the start of the primary vaccination series. The
results indicate an overall decline in antibody levels over time. Data on later time points (months 12
and 24) are not yet available.
Seroprotection*/
18 – 59 years
60 years and above
Seroneutralisation rate**
SRH Assay
MN Assay
SRH Assay
MN Assay
Month 6
28.1%
37.9%
26.7%
40.5%
*
SRH area
>
25 mm²
**
MN titre
>
20
To date a booster vaccination with homologous and heterologous vaccine strains has been
administered in the phase 3 study 6 months after primary vaccination with two doses of the
A/Vietnam/1203/2004 strain vaccine. Two dose levels (3.75 µg and 7.5 µg) of both the
A/Vietnam/1203/2004 and A/Indonesia/05/2005 strain vaccines were investigated for the booster
vaccination.
Seroprotective titres as determined by SRH assay against the homologous vaccine strain
(A/Vietnam/1203/2004) were observed in 65.5% of subjects aged 18 – 59 years and in 59.4% of
subjects aged 60 years and older at 21 days after a booster vaccination with the 7.5 μg dose of the
A/Vietnam strain vaccine. Twenty-one days after a booster vaccination with the 7.5 μg dose of the
7
a
MN titre
>
20
A/Indonesia/05/2005 strain vaccine a cross reactive response against the A/Vietnam strain was
obtained in 69.0% of subjects aged 18 – 59 years and in 40.6% of subjects aged 60 years and older.
Antibody responses as measured by MN 21 days after the booster vaccination were generally slightly
higher with the A/Indonesia/05/2005 than with the A/Vietnam/1203/2004 strain vaccine.
Seroneutralisation rates (MN titre
>
20) at 21 days after a booster vaccination with the 7.5 µg dose of
the A/Vietnam and A/Indonesia vaccines, tested against both the homologous and heterologous strains
were as follows:
6-Month Booster
18 – 59 years
60 years and above
Vaccination with 7.5 µg strain A/Vietnam
Tested against
A/Vietnam
A/Indonesia
A/Vietnam
A/Indonesia
Seroneutralisation rate*
86.2%
65.5%
64.5%
54.8%
Vaccination with 7.5 µg strain A/Indonesia
Seroneutralisation rate*
86.2%
93.1%
65.6%
71.9%
*
MN titer
>
1:20
Another study investigated a booster vaccination with 7.5 μg of the heterologous A/Indonesia/05/2005
vaccine strain administered 12 – 15 months after an initial 2-dose priming with various dose levels of
adjuvanted and non-adjuvanted formulations of the A/Vietnam/1203/2004 strain vaccine in subjects
aged 18 – 45 years. In subjects who received the 7.5 μg non-adjuvanted formulation for primary
vaccination (N = 12) seroprotection rates as measured by SRH 21 days after the booster vaccination
were 66.7% and 83.3%, and 100% and 91.7% of subjects achieved neutralising antibody titres
>
20
when tested against the homologous A/Indonesia and the heterologous A/Vietnam strain, respectively.
No clinical data have been generated in subjects below 18 years of age.
Information from non-clinical studies
The protective efficacy of PANDEMIC INFLUENZA VACCINE H5N1 BAXTER against morbidity
and mortality induced by the infection with lethal doses of highly pathogenic avian Influenza H5N1
virus was assessed non-clinically in a ferret challenge model. Two studies have been performed using
either the H5N1 A/Vietnam/1203/2004 or the A/Indonesia/05/2005 vaccine.
In one study, sixteen ferrets were divided into two cohorts and were vaccinated on days 0 and 21 with
7.5 µg of the A/Vietnam/1203/2004 vaccine or were sham vaccinated. All ferrets were challenged
intranasally on day 35 with a high dose of the highly virulent H5N1 virus strain A/Vietnam/1203/2004
and monitored for 14 days. Ferrets vaccinated with the 7.5 µg dose of the A/Vietnam/1203/2004
vaccine demonstrated a high rate of seroconversion. The A/Vietnam/1203/2004 vaccine afforded
protection against homologous challenge as evidenced by full survivorship, reduced weight loss, a less
pronounced and shorter increase in temperature, a less marked reduction in lymphocyte counts and in
reduction of inflammation and necrosis in brain and olfactory bulb in the vaccinated cohorts as
compared to control animals. All controls animals succumbed to the infection.
In a second study, sixty-six ferrets were divided into 6 cohorts of 11 ferrets and were immunized on
days 0 and 21 with 3.75 µg or 7.5 µg of the Indonesia vaccine or were sham vaccinated. The ferrets
were challenged intranasally on day 35 with a high dose of either the clade 2 H5N1 virus
A/Indonesia/05/2005 or the clade 1 H5N1 virus A/Vietnam/1203/2004 and monitored for 14 days. The
A/lndonesia/05/2005 vaccine was shown to be efficacious with 100% survival, reduced incidence of
fever, reduced weight loss, reduced virus burden, and reduced haematological (leukopenia and
lymphopenia) changes in the vaccinated cohorts following homologous challenge. Similarly, the
A/lndonesia/05/2005 vaccine was efficacious against a heterologous challenge, showing a vaccine
dose dependent survivorship in the vaccinated cohorts as compared to the control cohort. Similar to
the homologous challenge, vaccination against a heterologous challenge reduced virus burden, and
reduced haematological (leukopenia) changes associated with highly pathogenic avian influenza
infection.
8
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Non-Clinical studies demonstrated alterations in liver enzymes and calcium levels in repeat dose
toxicity studies in rats. Such alterations in liver function have not been seen to date in human clinical
studies. Alterations in calcium metabolism have not been examined in human clinical studies.
As of yet data from non-clinical studies concerning reproduction and development are not available.
6.1 List of excipients
Trometamol
Sodium chloride
Water for injections
Polysorbate 80
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.
6.3 Shelf-life
1 year
After first opening, the product should be used immediately. However, chemical and physical in-use
stability has been demonstrated for 3 hours at room temperature.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C).
Do not freeze.
Store in the original package in order to protect from light.
6.5 Nature and contents of the container
One pack of 20 multidose vials (type I glass) of 5 ml suspension (10 x 0.5 ml doses) with a stopper
(bromobutyl rubber)
6.6 Special precautions for disposal and other handling
The vaccine should be allowed to reach room temperature before use. Shake before use.
Each vaccine dose of 0.5 ml is withdrawn into a syringe for injection.
Any unused vaccine or waste material should be disposed of in accordance with local requirements.
9
7.
MARKETING AUTHORIZATION HOLDER
Baxter AG
Industriestrasse 67
A-1221 Vienna
Austria
8.
9.
Detailed information on this product is available on the website of the European Medicines Agency
(EMEA):
http://www.emea.europa.eu/
10
ANNEX II
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE
SUBSTANCE AND MANUFACTURING AUTHORISATION
HOLDER RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING
AUTHORISATION
C.
11
A.
MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturers of the biological active substance
Baxter BioScience s.r.o.
Jevany Bohumil 138
CZ-281 63 Kostelec nad Cernymi lesy
Czech Republic
Baxter AG
Uferstrasse 15
A-2304 Orth/Donau
Austria
Name and address of the manufacturer responsible for batch release
Baxter AG
Uferstrasse 15
A-2304 Orth/Donau
Austria
B.
CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to medical prescription.
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER can only be marketed when there is an
official WHO/EU declaration of an influenza pandemic, on the condition that the Marketing
Authorisation Holder for PANDEMIC INFLUENZA VACCINE H5N1 BAXTER takes due account
of the officially declared pandemic strain.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
•
OTHER CONDITIONS
Official batch release
In accordance with Article 114 Directive 2001/83/EC as amended, the official batch release will be
undertaken by a state laboratory or a laboratory designated for that purpose.
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, as described in version 1.15 (26 June
2009) presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and
functioning before and whilst the product is on the market.
12
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in version 003 (15 April 2009) of the Risk Management Plan
(RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent
updates of the RMP agreed by the CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the
updated RMP should be submitted at the same time as the next Periodic Safety Update Report
(PSUR).
In addition, an updated RMP should be submitted
•
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
•
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
•
At the request of the EMEA
Periodic Safety Update Reports
Outside of the pandemic period, the normal PSUR periodicity and format will be maintained, with a
specific review of AESI and possible adverse events related to adjuvants. This should include data
from ongoing studies, or actual use if applicable, of the ‘mock-up’ strains and any safety data relevant
to the adjuvant system.
During a pandemic situation, the resources must be concentrated on a timely and effective monitoring
of the safety profile of the influenza vaccines used during the pandemic. Moreover, a 6-monthly cycle
may be too long to allow assessment of the safety of a vaccine for which high levels of exposure are
expected within a short period of time. Therefore, 6-monthly or annual PSURs falling within the
pandemic period will be replaced by monthly “simplified PSURs” (S-PSUR) accompanied by a
summary of vaccine distribution.
Frequency of submission
-
The clock should start from the first Monday after shipment of the first batch of vaccine.
-
First data-lock point is 30 days later.
-
S-PSUR submission to the Rapporteur and CHMP members on Day 45.
-
Rapporteur’s assessment report is circulated to CHMP members on Day 50.
-
CHMP report is circulated to the vaccine manufacturer on Day 55.
-
Reporting to be monthly for the first 6 months.
-
Periodicity should be reviewed by the MAH and the (Co-)Rapporteur at 6 monthly intervals.
When it has been agreed by the CHMP that the S-PSUR is no longer necessary, a full PSUR covering
the period since the data lock point of the last routine PSUR will be submitted within a time frame to
be agreed with the Rapporteur.
Format of the simplified PSUR
Only spontaneously reported data should be included in the PSUR. The report should include the
following Tables of aggregate data (using the pre-defined templates attached in Annex 2).
1.
An overview for all spontaneous cases per country, stratified according to type of report
(medically confirmed or non-medically confirmed) and seriousness, for the period covered by
the report and cumulatively.
2.
An overview for all spontaneous adverse reactions by SOC, High Level Term (HLT) and
Preferred Term (PT), stratified according to type of report (medically confirmed or non-
medically confirmed) and including the number of fatal reports, for the period covered by the
report and cumulatively.
13
3.
Adverse Events of Special Interest stratified according to type of report (medically confirmed
or non-medically confirmed). AESIs will be defined as follows:
-
Neuritis: PT “Neuritis”
-
Convulsion: narrow SMQ “Convulsions”
-
Anaphylaxis: narrow SMQ “Anaphylactic reaction” and narrow SMQ
“Angioedema”
-
Encephalitis: narrow SMQ “Non-infectious encephalitis”
-
Vasculitis: narrow SMQ “Vasculitis”
-
Guillain-Barré syndrome: narrow SMQ “Guillain-Barré syndrome”
-
Demyelination:
narrow SMQ “Demyelination” (as GBS is also included in
this SMQ, there will be an overlap in the number of cases for
these two categories).
-
Bell’s palsy:
PT “Bell’s palsy”
-
Vaccination failure:
PT “Vaccination failure”.
4.
Serious unlisted adverse reactions (SOC, HLT, PTs) stratified according to type of report
(medically confirmed or non-medically confirmed), for the period covered by the report and
cumulatively.
5.
All spontaneous adverse reactions by age group, per SOC, HLT and PT, stratified according to
type of report (medically confirmed or non-medically confirmed), for the period covered by
the report and cumulatively. The following age groups will be used: < 2 years, 2-8 years,
>
9
years.
6.
All spontaneous adverse reactions (SOC, HLT, PT) occurring in pregnant women, stratified
according to type of report (medically confirmed or non-medically confirmed), for the period
covered by the report and cumulatively.
The following principles should be followed when compiling the data:
-
Except for Table 1, all tables will be based on number of reactions (presented on PT level,
sorted by System Organ Class [SOC] and High Level Term [HLT]) and not number of cases.
-
be evaluated during signal work-up.
-
“Cumulatively” means since the use of the vaccine; events not reported during the period of
interest should not be presented in the tables.
-
All non-medically confirmed events are those that have been entered into the database by the
data-lock point. Those which have not yet been entered should be reported in the following S-
PSUR.
-
-
A line listing of fatal cases will be provided in an Annex.
A short summary should be provided in which validated signals and areas of concern are highlighted,
taking into account information arising from the prospective cohort study described in 4.5. In the
event of multiple signals, signal work-up may be prioritised and appropriate timelines for submission
of a full signal evaluation report should be provided.
Vaccine distribution report
1
Based on the assumption that product name will not be provided in a significant proportion of cases.
14
To put the safety report into context, a summary of vaccine distribution should be included and should
provide details of the number of doses of vaccine distributed in
i)
EU member states for the reporting period by batch number,
ii)
EU member states cumulatively and
iii)
the rest of the world.
C.
SPECIFIC OBLIGATIONS TO BE FULFILLED BY THE MARKETING
AUTHORISATION HOLDER
The Marketing Authorisation Holder shall complete the following programme of studies within the
specified time frame, the results of which shall form the basis of the annual reassessment of the
benefit/risk profile in case the Pandemic will be declared.
Area
Description
Due date
Clinical
During the pandemic, the applicant will
collect clinical safety and effectiveness data of
the pandemic vaccine and submit this
information to the CHMP for evaluation.
Depending on and after
implementation of vaccine
when first pandemic will
take place.
Pharmacovigilance During the pandemic, the applicant will
conduct a prospective cohort study as
identified in the Pharmacovigilance plan.
Depending on and after
implementation of vaccine
when first pandemic will
take place.
15
ANNEX III
LABELLING AND PACKAGE LEAFLET
16
A. LABELLING
17
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON
1.
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER, suspension for injection
Pandemic influenza vaccine (whole virion, Vero cell derived, inactivated)
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Whole virus influenza vaccine, inactivated containing antigen of pandemic strain*:
A/Vietnam/1203/2004 (H5N1)
7.5 microgram**
per 0.5 ml dose
* propagated in Vero cells (continuous cell line of mammalian origin)
** expressed in micrograms haemagglutinin
3.
LIST OF EXCIPIENTS
Trometamol,
sodium chloride,
water for injections,
polysorbate 80
4.
Suspension for injection.
20 multidose vials (10 doses per vial – 0.5 ml per dose)
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Intramuscular use.
The vaccine should be allowed to reach room temperature before use.
Shake before use.
After first opening, the vial is to be used within a maximum of 3 hours.
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.
18
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
Do not inject intravascularly.
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Store in refrigerator.
Do not freeze.
Store in the original package in order to protect from light.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Dispose of in accordance with local requirements.
Baxter AG
Industriestrasse 67
A-1221 Vienna
Austria
EU/0/00/000/000
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Justification for not including Braille accepted.
19
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
LABEL FOR 10-DOSE VIAL
1.
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER suspension for injection
Pandemic influenza vaccine (whole virion, Vero cell derived, inactivated)
I.M.
2.
METHOD OF ADMINISTRATION
Shake before use
3.
EXPIRY DATE
EXP
4.
BATCH NUMBER
Lot
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
Multidose vial (10 doses of 0.5 ml per vial)
6.
OTHER
After first opening, the vial is to be used within a maximum of 3 hours.
BAXTER AG
A-1221 Vienna
Austria
20
B. PACKAGE LEAFLET
21
PACKAGE LEAFLET: INFORMATION FOR THE USER
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
suspension for injection
Pandemic influenza vaccine (whole virion, Vero cell derived, inactivated)
Read all of this leaflet carefully before you start receiving this vaccine.
-
Keep this leaflet. You may need to read it again.
-
If you have any further questions, ask your doctor or pharmacist.
This vaccine has been prescribed for you. Do not pass it on to others.
-
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 PANDEMIC INFLUENZA VACCINE H5N1 BAXTER is and what it is used for
2.
Before you receive PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
3.
How PANDEMIC INFLUENZA VACCINE H5N1 BAXTER is given
4.
Possible side effects
5.
How to store PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
6.
Further information
1.
WHAT PANDEMIC INFLUENZA VACCINE H5N1 BAXTER IS AND WHAT IT IS
USED FOR
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER is a vaccine used in adults of 18 years of age
and older. It is used to prevent influenza (flu) in an officially declared pandemic.
Pandemic flu is a type of influenza that occurs every few decades and which spreads rapidly to affect
most countries and regions around the world. The symptoms (signs) of pandemic flu are similar to
those of an “ordinary” flu but are usually more severe.
The vaccine works by helping the body to produce its own protection (antibodies) against the disease.
2.
BEFORE YOU RECEIVE PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
Do not use PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
•
if you previously had a serious allergic reaction (i.e. life-threatening) to PANDEMIC
INFLUENZA VACCINE H5N1 BAXTER.
•
if you are allergic to any of the ingredients or trace residues (formaldehyde, benzonase, sucrose)
contained in the vaccine. The active substance and other ingredients in PANDEMIC
INFLUENZA VACCINE H5N1 BAXTER are listed in Section 6 at the end of the leaflet. Signs
of an allergic reaction may include itchy skin rash, shortness of breath and swelling of the face
or tongue. However, in a pandemic situation, your doctor may recommend to give the vaccine.
Take special care with PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
You should tell your doctor before vaccination
•
if you have a severe infection with a high temperature (over 38°C). If this applies to you then
your vaccination will usually be postponed until you are feeling better. A minor infection such
22
as a cold should not be problem, but your doctor should advise whether you could still be
vaccinated with PANDEMIC INFLUENZA VACCINE H5N1 BAXTER.
•
if you have a poor immune response (as for example because of immunosuppressive therapy,
e.g. corticosteroid treatments or chemotherapy for cancer);
•
if you are having a blood test to look for evidence of infection with certain viruses. In the first
few weeks after vaccination with PANDEMIC INFLUENZA VACCINE H5N1 BAXTER the
results of these tests may not be correct. Tell the doctor requesting these tests that you have
recently received PANDEMIC INFLUENZA VACCINE H5N1 BAXTER;
•
If you have a bleeding problem or bruise easily.
There is no information on the use of PANDEMIC INFLUENZA VACCINE H5N1 BAXTER below
18 years of age. In case of pandemic national recommendations will be followed.
Taking other medicines
•
Please tell your doctor if you are taking or have recently taken any other medicines, including
medicines obtained without a prescription or have recently received any other vaccine.
•
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER should not be given at the same time as
other vaccines. However, if this cannot be avoided, the other vaccine should be injected into the
other limb. You should be aware that the side effects may be intensified.
•
If you take any medicines that reduce immunity to infections or have any other type of
treatment (such as radiotherapy) that affects the immune system, PANDEMIC INFLUENZA
VACCINE H5N1 BAXTER can still be given but your response to the vaccine may be poor.
•
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER should not be given at the same time as
immunoglobulins. However, if this cannot be avoided, the immunoglobulins should be injected
into the other limb.
Pregnancy and breast-feeding
Tell your doctor if you are pregnant, think you may be pregnant, plan to become pregnant, or are
breast-feeding. Your doctor will decide if you should receive PANDEMIC INFLUENZA VACCINE
H5N1 BAXTER.
Driving and using machines
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER may make you feel dizzy or sick which may
affect your ability to drive or use machines.
3. HOW PANDEMIC INFLUENZA VACCINE H5N1 BAXTER IS GIVEN
Adults from the age of 18 years and older will receive two injections of PANDEMIC INFLUENZA
VACCINE H5N1 BAXTER. The time period between the first and the second injection must be at
least three weeks.
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER is given as an injection into the muscle
(usually in the upper arm).
The vaccine should never be given into a vein.
If you have any further questions on the use of this product, ask your doctor or pharmacist.
23
4.
POSSIBLE SIDE EFFECTS
Like all medicines, PANDEMIC INFLUENZA VACCINE H5N1 BAXTER can cause side effects,
although not everybody gets them.
In the clinical studies with PANDEMIC INFLUENZA VACCINE H5N1 BAXTER, most side effects
were mild in nature and short term. The side-effects are generally similar to those related to the
influenza vaccine. There were fewer side effects after the second vaccination compared with the first.
The most frequently occurring side effect was injection site pain, which was usually mild.
The following side effects have been reported in clinical studies.
The frequency of possible side effects listed below is defined using the following convention:
very common (affects more than 1 user in 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
rare (affects 1 to 10 users in 10,000)
very rare (affects less than 1 user in 10,000)
not known (frequency cannot be estimated from the available data).
Very common
:
•
pain at the injection site
Common
:
•
runny nose and sore throat,
•
headache, dizziness, vertigo (motion sickness)
•
sweating more than usual,
•
joint or muscle pain,
•
chills, fatigue (feeling tired), malaise (generally feeling unwell), fever,
•
tissue hardening, redness, swelling or bruising at the injection site
Uncommon
:
•
swollen glands,
•
insomnia (difficulty sleeping), restlessness,
•
impaired perception of touch, pain, heat and cold, sleepiness,
•
conjunctivitis (an inflammation of the eye),
•
sudden hearing loss,
•
reduced blood pressure,
•
shortness of breath, cough, congestion of the nose,
•
nausea, vomiting, diarrhoea, stomach pain,
•
rash, itching,
•
irritation at the injection site
Other side effects which have occurred in the days or weeks after vaccination with flu vaccines
include:
Uncommon:
•
Generalized skin reactions such as itching, hives or rash
Rare:
•
Nerve pain (neuralgia)
•
Tingling and numbness
•
Fits
•
Transient low blood platelet count
24
•
Allergic reactions, in rare cases leading to shock (a dangerous decrease of blood pressure,
which, if untreated, may lead to collapse, coma and death)
Very rare:
•
Inflammation of blood vessels (vasculitis) with s transient kidney problems
•
Inflammation of the brain and spinal chord (encephalomyelitis)
•
Temporary inflammation of the nerves, causing pain, weakness and paralysis in the extremities
and often progressing to the chest and face
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.
5.
HOW TO STORE PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
Keep out of the reach and sight of children.
Do not use PANDEMIC INFLUENZA VACCINE H5N1 BAXTER after the expiry date which is
stated on the carton. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
Store in the original package in order to protect from light.
Do not freeze.
After first opening the vial is to be used within a maximum of 3 hours.
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 PANDEMIC INFLUENZA VACCINE H5N1 BAXTER contains
Active substance:
Whole virion influenza vaccine, inactivated, containing antigen of pandemic strain*:
A/Vietnam/1203/2004 (H5N1)
7.5 micrograms**
per 0.5 ml dose
* propagated in Vero cells (continuous cell line of mammalian origin)
** haemagglutinin
The other ingredients are: trometamol, sodium chloride, water for injections, polysorbate 80.
What PANDEMIC INFLUENZA VACCINE H5N1 BAXTER looks like and contents of the pack
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER is an off-white, opalescent, translucent liquid.
1 pack of PANDEMIC INFLUENZA VACCINE H5N1 BAXTER contains 20 multidose vials of 5 ml
suspension for injection for 10 doses.
25
Marketing Authorisation Holder:
Baxter AG
Industriestrasse 67
A-1221 Vienna
Austria
Manufacturer:
Baxter AG
Uferstrasse 15
A-2304 Orth/Donau
Austria
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder given below:
België/Belgique/Belgien
Baxter Belgium SPRL
Bd. de la Plaine/Pleinlaan 5
B-1050 Brussel/Bruxelles/Brüssel
Tél/Tel: + 32 2 650 1711
Luxembourg/Luxemburg
Baxter Belgium SPRL
Bd. de la Plaine/Pleinlaan 5
B-1050 Bruxelles/Brüssel
Tél/Tel: + 32 2 650 1711
България
ТП Бакстер АД
ул. Рачо Димчев 4
София 1000
тел.: + 359 2 9808482
Magyarország
Baxter Hungary Kft
Népfürdő u. 22.
H-1138 Budapest
Tel.: +361 202 19 80
Česká republika
Baxter Czech spol.s r.o.
Opletalova 55
CZ-110 00 Praha 1
Tel.: +420 225774111
Malta
Baxter Healthcare Ltd
Wallingford Road, Compton Newbury
Berkshire RG20 7QW - UK
Tel.: + 44 1635 206345
Danmark
Baxter A/S
Gydevang 43
DK-3450 Allerød
Tlf: + 45 48 16 64 00
Nederland
Baxter B.V.
Kobaltweg 49
NL-3542 CE Utrecht
Tel: + 31 30 2488911
Deutschland
Baxter Deutschland GmbH
Edisonstraße 4
D-85716 Unterschleißheim
Tel: + 49 89 31701-0
Norge
Baxter AS
Gjerdrumsvei 11
N-0484 Oslo
Tlf: + 47 22 58 4800
Eesti
AS Oriola
Kungla 2
EE-76505 Saue
Tel.: + 372 6 515 100
Österreich
Baxter Vertriebs GmbH
Landstraβer Hauptstraβe 99 /Top 2A
A-1031 Wien
Tel.: +43 1 71120 0
26
Ελλάδα
Baxter (Hellas) Ε.Π.Ε.
Εθνάρχου Μακαρίου 34 & Αθηνοδώρου
Ηλιούπολη
GR-163 41 Αθήνα
Τηλ.: +30-210-99 87 000
Polska
Baxter Polska Sp. z o.o.
ul. Kruczkowskiego 8
PL-00-380 Warszawa
Tel.: + 48 22 4883 777
España
Baxter S.L.
Pouet de Camilo, 2
E- 46394 Ribarroja del Turia (Valencia)
Tel: + 34 96 2722800
Portugal
Baxter Médico Farmacêutica Lda
Sintra Business Park
Zona Industrial da Abrunheira, Edifício 10
P-2710-089 Sintra
Tel: + 351 21 925 25 00
France
Baxter SAS
6 Avenue Louis Pasteur
F-78310 Maurepas
Tél: + 33 1 3461 5050
România
FARMACEUTICA REMEDIA S.A.
78 Metalurgiei Blv., 4th district
041836 Bucharest, ROMANIA
Tel.: + 40-21-321 1640
Ireland
Baxter Healthcare Ltd
Unit 7 Deansgrange Industrial Estate
IRL-Blackrock, Dublin
Tel: + 44 1635 206345
Slovenija
Baxter d.o.o.
Železna cesta 14
1000 Ljubljana
Tel.: + 386 1 420 16 80
Ísland
Icepharma hf.
Lynghálsi 13
IS-110 Reykjavík
Sími: + 354 540 80-00
Slovenská republika
Baxter AG, o. z.
Dúbravská cesta 2
SK-841 04 Bratislava
Tel: + 421 2 59418455
Italia
Baxter S.p.A.
Piazzale dell’Industria, 20
I-00144 Roma
Tel: + 39 06 324911
Suomi/Finland
Baxter Oy
PL 270
Valimotie 15 A
FIN-00381 Helsinki
Puh/Tel: + 358 9 8621111
Κύπρος
Baxter (Hellas) Ε.Π.Ε.
Εθνάρχου Μακαρίου 34 & Αθηνοδώρου
Ηλιούπολη
GR-163 41 Αθήνα
Τηλ.: +30-210-99 87 000
Sverige
Baxter Medical AB
Torshamnsgatan 35
Box 63
S-164 94 Kista
Tel: + 46 8 6326400
Latvija
Baxter AG Latvijas filiāle
Dzelzavas iela 117
LV 1021 RĪGA
Tel.: +371 67784784
United Kingdom
Baxter Healthcare Ltd
Wallingford Road, Compton Newbury
Berkshire RG20 7QW - UK
Tel: + 44 1635 206345
27
Lietuva
UAB TAMRO atstovybė
S. Žukausko g. 29-1
LT-09129 Vilnius
Tel.: + 370 5 269 16 91
This leaflet was last approved
in
{MM/YYYY}.
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER has been authorised under “exceptional
circumstances”. This means that for scientific reasons, it has been impossible to get complete
information on this medicine. The European Agency (EMEA) will review any new information on the
medicine every year and this leaflet will be updated as necessary.
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web
---------------------------------------------------------------------------------------------------------------------------
The following information is intended for medical or health care professionals only:
Prior to administration, the vaccine should be allowed to reach room temperature and the vial should
be shaken well.
After first opening, the vial is to be used within a maximum of 3 hours.
Each vaccine dose of 0.5 ml is withdrawn into a syringe for injection.
The vaccine should not be administered intravascularly.
Any unused vaccine or waste material should be disposed of in accordance with local requirements.”
28
Source: European Medicines Agency
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