Summary of medicine characteristics - Pandemic Influenza Vaccine H5N1 Baxter AG
1. NAME OF THE MEDICINAL PRODUCT
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER
Suspension for injection
Pandemic influenza vaccine (H5N1) (whole virion, inactivated, prepared in cell culture)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Influenza vaccine (whole virion, inactivated) containing antigen * of:
A/Vietnam/1203/2004 (H5N1) 7.5 micrograms**per
0.5 ml dose
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* produced in Vero cells
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* * haemagglutinin
This vaccine complies with the WHO recommendation and EU decision for the pandemic.
The vaccine is available in a multidose container (see section 6.5 for the number of doses per vial).
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Suspension for injection.
The vaccine is an off-white, opalescent, translucent suspension.
4. CLINICAL PARTICULARS4.1 Therapeutic indications
Prophylaxis of influenza in an officially declared pandemic situation. Pandemic influenza vaccine should be used in accordance with official guidance.
4.2 Posology and method of administration
Posology
Adults and children from 6 months onwards:
One 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.
Method of administration
Immunization should be carried out by intramuscular injection into the deltoid muscle or anterolateral thigh, depending on the muscle mass.
For further information, see section 5.1.
4.3 Contraindications
History of an anaphylactic (i.e. life-threatening) reaction to the active substance, to any of the excipients listed in section 6.1 or to 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.
4.4 Special warnings and precautions for use
- • Hypersensitivity reactions, including anaphylaxis, have been reported following use of a similar whole virion, Vero cell derived H1N1 influenza vaccine administered during a pandemic period. Such reactions occurred both in patients with a history of multiple allergies and in patients with no known allergy.
- • Caution is needed when administering this vaccine to persons with a known hypersensitivity (other than anaphylactic reaction) to the active substance, 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).
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4.5 Interactions with other medicinal products and other forms of interaction
- • 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.
4.6 Fertility, pregnancy and lactation
The safety of PANDEMIC INFLUENZA VACCINE H5N1 BAXTER in pregnancy and lactation has not been assessed in clinical trials. Data from pregnant women vaccinated with different inactivated non-adjuvanted seasonal vaccines do not suggest malformations or foetal or neonatal toxicity.
Animal reproductive and developmental toxicity studies with H5N1 strain vaccines (A/Vietnam/1203/2004 and A/Indonesia/05/2005) do not indicate direct or indirect harmful effects with respect to female fertility, pregnancy, embryonal/foetal development, parturition or post-natal development (see section 5.3).
The use of PANDEMIC INFLUENZA VACCINE H5N1 BAXTER may be considered during pregnancy if this is thought to be necessary, taking into account official recommendations. PANDEMIC INFLUENZA VACCINE H5N1 BAXTER may be used in lactating women.
Health care providers should carefully consider the potential risks and benefits for each specific patient before administering PANDEMIC INFLUENZA VACCINE H5N1 BAXTER.
4.7 Effects on ability to drive and use machines
Some undesirable effects mentioned under section 4.8 such as dizziness and vertigo may affect the ability to drive or use machines.
4.8 Undesirable effects
Summary of safety profile
Adults, older people and special risk groups
Clinical trials were conducted with this H5N1 vaccine (see section 5.1 for more information on the H5N1 vaccines) in approximately 3500 subjects (ranging in age groups from 18 to 59 years and 60 years and above) and special risk groups of approximately 300 subjects each, consisting of immunocompromised subjects and patients with chronic disease conditions.
The safety profile in immunocompromised subjects and patients with chronic disease conditions is similar to the safety profile in healthy adults and older subjects.
Infants, children, and adolescents
Children and adolescents aged 3 to 17 years:
In a clinical trial 300 adolescents aged 9 to 17 years and 153 children aged 3 to 8 years were administered the H5N1 vaccine. The incidence and nature of symptoms after the first and second vaccination were similar to those observed in the healthy adults and older subjects.
Infants and children aged 6 to 35 months:
In a clinical trial the H5N1 vaccine was administered to 36 infants and children aged 6 to 35 months.
Adverse reactions are listed according to the following frequency below.
Summary of adverse reactions
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)
Adults and older people:
| Adverse Reactions (Adults and Older People) | ||
| System Organ Class (SOC) | Preferred MedDRA Term | Frequency |
| INFECTIONS AND INFESTATIONS | Nasopharyngitis | Common |
| BLOOD AND LYMPHATIC SYSTEM DISORDERS | Lymphadenopathy | Uncommon |
| PSYCHIATRIC DISORDERS | Insomnia | Uncommon |
| NERVOUS SYSTEM DISORDERS | Headache Dizziness Somnolence Sensory disturbance (paresthesia, dysesthesia, oral dysesthesia, hypoesthesia, dysgeusia, and burning sensation) Syncope | Very common Uncommon Uncommon Common Uncommon |
| EYE DISORDERS | Conjunctivitis Eye irritation | Uncommon Uncommon |
| EAR AND LABYRINTH DISORDERS | Vertigo Ear pain Sudden hearing loss | Common Uncommon Uncommon |
| VASCULAR DISORDERS | Hypotension | Uncommon |
| RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS | Oropharyngeal pain Cough Dyspnea Nasal congestion Rhinorrhea Dry throat | Common Common Uncommon Uncommon Uncommon Uncommon |
| GASTROINTESTINAL DISORDERS | Diarrhea Vomiting Nausea Abdominal pain Dyspepsia | Common Uncommon Uncommon Uncommon Uncommon |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | Hyperhidrosis Pruritis Rash Urticaria | Common Common Uncommon Uncommon |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | Arthralgia Myalgia | Common Common |
| GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS | Fatigue Pyrexia Chills Malaise Influenza-like illness Chest discomfort Injection Site Reactions
| Very Common Common Common Common Uncommon Uncommon Very Common Common Common Common Common Uncommon Uncommon Uncommon |
Infants, children and adolescents :
| Adverse Reactions (Infants, Children and Adolescents) | ||||
| System Organ Class (SOC) | Preferred MedDRA Term | Frequency | ||
| 6 – 35 months | 3 – 8 years | 9 – 17 years | ||
| INFECTIONS AND INFESTATIONS | Nasopharyngitis | Common | Common | Common |
| METABOLISM AND NUTRITION DISORDERS | Decreased appetite | Common | Uncommon | Uncommon |
| PSYCHIATRIC | Insomnia | – | – | Uncommon |
| DISORDERS | Sleep disorder | Common | – | – |
| NERVOUS SYSTEM | Dizziness | – | – | Uncommon |
| DISORDERS | Headache | – | Common | Very Common |
| Crying | Common | – | – | |
| Somnolence | Very Common | – | – | |
| Hypoaesthesia | – | – | Uncommon | |
| EYE DISORDERS | Eye irritation | – | Uncommon | – |
| EAR AND LABYRINTH DISORDERS | Vertigo | – | – | Uncommon |
| RESPIRATORY, | Cough | – | Uncommon | Uncommon |
| THORACIC AND | Oropharyngeal pain | – | Common | Common |
| MEDIASTINAL DISORDERS | Rhinorrhoea | – | Uncommon | Uncommon |
| GASTROINTESTINAL | Abdominal pain | – | – | Common |
| DISORDERS | Nausea | Common | Common | Common |
| Vomiting | Common | Common | Common | |
| Diarrhoea | Common | Uncommon | Uncommon | |
| SKIN AND | Hyperhidrosis | Common | Uncommon | Common |
| SUBCUTANEOUS TISSUE DISORDERS | Pruritus | – | – | Uncommon |
| MUSCULOSKELETAL | Arthralgia | – | Common | Common |
| AND CONNECTIVE | Myalgia | – | Common | Common |
| TISSUE DISORDERS | Pain in extremity | – | – | Uncommon |
| GENERAL DISORDERS | Injection site pain | Very common | Very common | Very common |
| AND ADMINISTRATION | Injection site induration | Common | Common | Common |
| SITE CONDITIONS | Injection site erythema | Common | Common | Common |
| Injection site swelling | Common | Common | Common | |
| Injection site hemorrhage | Common | Common | Uncommon | |
| Injection site pruritus | – | Uncommon | Uncommon | |
| Axillary pain | – | Uncommon | Uncommon | |
| Fatigue | – | Common | Common | |
| Pyrexia | Very Common | Common | Uncommon | |
| Chills | – | – | Common | |
| Irritability | Very Common | – | – | |
| Malaise | – | Common | Common | |
| Feeling Cold | – | Uncommon | Uncommon | |
Post-marketing surveillance
For PANDEMIC INFLUENZA VACCINE H5N1 BAXTER post-marketing surveillance data are not yet available.
Class effects :
From post-marketing surveillance with a whole virion, Vero cell derived, H1N1 vaccine, the following adverse reactions have been reported (the frequency of these adverse reactions is not known as it cannot be estimated from the available data):
Immune system disorders: anaphylactic reaction, hypersensitivity
Nervous system disorders: convulsion
Skin and subcutaneous tissue disorders: angioedema
Musculoskeletal and connective tissue disorders: pain in extremity
Trivalent seasonal influenza vaccines
The following serious adverse reactions have been reported from post-marketing surveillance with egg-derived interpandemic trivalent vaccines:
Uncommon: generalised skin reactions
Rare: neuralgia, transient thrombocytopenia
Very rare: vasculitis with transient renal involvement. Neurological disorders, such as encephalomyelitis, neuritis and Guillain Barré syndrome
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in
4.9 Overdose
No case of overdose has been reported.
5. PHARMACOLOGICAL PROPERTIES5.1 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 (EMA) will review any new information which may become available every year and this SmPC will be updated as necessary.
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.
Adults, older people and special risk groups
Immune response against the vaccine strain contained in PANDEMIC INFLUENZA VACCINE H5N1 BAXTER (A/Vietnam/1203/2004)
The immunogenicity of PANDEMIC INFLUENZA VACCINE H5N1 BAXTER (strain A/Vietnam/1203/2004) has been evaluated in three clinical studies in adults aged 18 – 59 years (N=961) and in older subjects aged 60 years and older (N=391) following a 0, 21 day schedule.
In addition, the immunogenicity has also been evaluated in a Phase 3 study in specified risk groups of immunocompromised subjects (N=122) and patients with chronic disease conditions (N=123) following a 0, 21 day schedule.
Immunogenicity in adults aged 18 to 59 years (N=961) and in subjects aged 60 years and
older (N=391)
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 older subjects aged 60 years and above were as follows:
| SRH Assay | 18 – 59 years 21 Days After | 60 years and above 21 Days After | ||
| 1st Dose | 2nd Dose | 1st Dose | 2nd Dose | |
| Seroprotection rate* | 53.2% | 66.8% | 47.7% | 59.0% |
| Seroconversion rate | 39.8% | 53.7% | 41.9% | 52.2% |
| Seroconversion factor | 2.5 | 3.4 | 2.7 | 3.5 |
SRH area > 25 mm2
either SRH area > 25 mm2 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 neutralising antibody titres > 20, seroconversion rate and seroconversion factor as measured by microneutralisation assay (MN) in adults aged 18 to 59 years and in older subjects aged 60 years and above were as follows:
| Microneutralisation assay | 18 – 59 years 21 Days After | 60 years and above 21 Days After 1st Dose 2nd Dose | |
| 1st Dose | 2nd Dose | ||
| Seroneutralisation rate | 44.4% | 69.7% | 51.9% 69.2% |
| Seroconversion rate | 32.7% | 56.0% | 13.3% 23.9% |
| Seroconversion factor | 3.0 | 4.5 | 2.0 2.6 |
| * MN titre > 20 | |||
| > 4-fold increase in MN titre | |||
| geometric mean increase | |||
Immunogenicity in immunocompromised subjects (N=122) and in patients with chronic disease conditions (N=123)
After vaccination the rate of subjects with neutralising antibody titres > 20, seroconversion rate and seroconversion factor as measured by MN assay in immunocompromised subjects and patients with chronic disease conditions were as follows:
| Microneutralisation Assay | Immunocompromised subjects 21 Days After | Patients with chronic disease conditions 21 Days After | ||
| 1st Dose | 2nd Dose | 1st Dose | 2nd Dose | |
| Seroneutralisation rate* | 24.8% | 41.5% | 44.3% | 64.2% |
| Seroconversion rate | 9.1% | 32.2% | 17.2% | 35.0% |
| Seroconversion factor | 1.6 | 2.5 | 2.3 | 3.0 |
* MN titre > 20
> 4-fold increase in MN titre
geometric mean increase
Antibody persistence
Antibody persistence after vaccination with the 7.5 ^g non-adjuvanted formulation of
PANDEMIC INFLUENZA VACCINE H5N1 BAXTER (strain A/Vietnam/1203/2004) has been evaluated in a clinical study in adults aged 18 – 59 years and subjects aged 60 years and above at 6 months, 12 – 15 months and 24 months after the start of the primary vaccination series.
The results indicate an overall decline in antibody levels over time.
| Seroprotection*/ 18 – 59 years Seroneutralisation rate** SRH Assay MN Assay | 60 years and above SRH Assay MN Assay |
| Month 6 23.9% 35.0% Month 12–15 20.7% 34.2% Month 24 22.4% 18.4% | 26.7% 40.5% 18.9% 36.2% 12.3% 22.8% |
* SRH area > 25 mm2
** MN titre > 20
Cross-reactive immune response against related H5N1 strains
In a phase 3 study in adults (N=270) and older subjects (N=272) 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:
| Tested against | 18 – 59 years | 60 years and above | ||
| Day 42 a | Day 180 Strain A/Indo: | Day 42 a nesia/05/2005 | Day 180 | |
| Seroneutralisation rate* | 35.1% | 14.4% | 54.8% | 28.0% |
| * MN titre > 20 a 21 days after 2nd dose | ||||
Heterologous booster vaccinations
A booster vaccination with a 7.5 ^g heterologous A/Indonesia/05/2005 vaccine strain has been administered in a time window of 12 to 24 months after priming vaccination with two doses of the A/Vietnam/1203/2004 strain vaccine in three clinical studies in adults aged 18 to 59 years and in older people aged 60 years and above. A 12 to 24 months heterologous booster has also been administered in a phase 3 study in immunocompromised subjects and patients with chronic disease conditions.
Seroneutralisation rates (MN titre > 20) at 21 days after a 12 to 24 months booster vaccination with the 7.5 ^g dose of the A/Indonesia/05/2005 strain vaccine, tested against both the homologous and heterologous strains were as follows:
| Seroneutralisation rate* Tested against | 18 – 59 years A/Vietnam A/Indones: | 60 years and above ia A/Vietnam A/Indonesia |
| 12 – 24 months booster | 89.8% 86.9% | 82.9 % 75.3% |
| * MN titre > 20 | ||
| Seroneutralisation rate* Tested against | Immunocompromised subjects A/Vietnam A/Indonesia | Patients with chronic disease conditions A/Vietnam A/Indonesia |
| 12 – 24 months booster | 71.6% 65.7% | 77.5% 70.8% |
| * MN titre > 20 | ||
Infants, children, and adolescents
Immune response against A/Vietnam/1203/2004 (H5N1)
The immunogenicity of the A/Vietnam/1203/2004 strain vaccine has been evaluated in a clinical trial in children and adolescents aged 9 to 17 years (N=288), in children aged 3 to 8 years (N=146) and in infants and children aged 6 to 35 months (N=33) following a 0, 21 day schedule.
After vaccination, the seroprotection rate, seroconversion rate, and seroconversion factor for anti-HA antibody, as measured by SRH, in, infants, children, and adolescents aged 6 months to 17 years were as follows:
| SRH assay | 9 – 17 years 21 Days after 1st Dose 2nd Dose | 3 – 8 years 21 Days after | 6 – 35 months 21 Days after | ||
| 1st Dose | 2nd Dose | 1st Dose | 2nd Dose | ||
| Seroprotection rate* | 63.8% 75.1% | 46.1% | 75.4% | 13.8% | 63.0% |
| Seroconversion rate | 48.4% 63.5% | 43.3% | 78.3% | 13.8% | 77.8% |
| Seroconversion factor | 3.3 4.7 | 2.9 | 5.9 | 1.4 | 4.6 |
| * SRH area > 25 mm2 | |||||
either SRH area > 25 mm2 if baseline sample negative or 50% increase in SRH area if baseline sample >4 mm2
geometric mean increase
After vaccination, the rate of subjects with neutralizing antibody titers > 20, seroconversion rate and seroconversion factor, as measured by MN assay, in infants, children, and adolescents aged 6 months to 17 years were as follows:
| MN assay | 9 – 17 years 21 Days after 1st Dose 2nd Dose | 3 – 8 years 21 Days after | 6 – 35 months 21 Days after | ||
| 1st Dose | 2nd Dose | 1st Dose | 2nd Dose | ||
| Seroneutralization rate* | 52.6% 85.4% | 17.1% | 72.9% | 3.0% | 68.8% |
| Seroconversion rate | 9.1% 31.8% | 16.4% | 72.2% | 9.1% | 65.6% |
| Seroconversion factor | 1.6 3.1 | 2.1 | 6.3 | 1.4 | 6.8 |
|
| MN titer > 20 > 4-fold increase in MN titer |
| geometric mean increase |
Heterologous Booster Vaccinations
A heterologous booster vaccination with a 7.5 ^g non-adjuvanted formulation of the A/Indonesia/05/2005 strain vaccine has been administered 12 months after a priming vaccination with two doses of the A/Vietnam/1203/2004 strain vaccine in children and adolescents aged 9 to 17 years (N=196), children aged 3 to 8 years (N=79) and infants and children aged 6 months to 35 months (N=25).
Seroprotection rates (SRH area > 25 mm2) at 21 days after a 12 months booster vaccination with the 7.5 mcg dose of the A/Indonesia/05/2005 strain vaccine, tested against both the homologous and heterologous strains, were as follows:
| Seroprotection rate 9 – 17 years 3 – 8 years Tested against A/Vietnam A/Indonesia A/Vietnam A/Indonesia | 6 – 35 months A/Vietnam A/Indonesia |
| 12 Month Booster 81.6% 86.2% 87.5% 86.1% | 96.0% 96.0% |
SRH area > 25 mm2
Seroneutralization rates (MN titer > 20) at 21 days after a booster vaccination with the 7.5 ^g dose of the A/Indonesia/05/2005 strain vaccine, tested against both the homologous and heterologous strains, were as follows:
| Seroneutralization rate* Tested against | 9 – 17 A/Vietnam | years A/Indonesia | 3 – 8 years A/Vietnam A/Indonesia | 6 – 35 months A/Vietnam A/Indonesia |
| 12 Month Booster | 94.1% | 93.1% | 94.7% 97.2% | 100.0% 100.0% |
* MN titer > 20
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 ^g 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 ^g 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 control 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 ^g or 7.5 ^g 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.
5.2 Pharmacokinetic properties
Not applicable.
5.3 Preclinical safety data
Non-clinical studies demonstrated minor alterations in liver enzymes and calcium levels in a repeat dose toxicity study in rats. Clinically significant alterations in liver enzymes and calcium levels have not been seen to date in human clinical studies.
Animal reproductive and developmental toxicity studies do not indicate direct or indirect harmful effects with respect to female fertility, pregnancy, embryonal/ foetal development parturition or post natal development. Male fertility was not investigated in the reproductive and developmental toxicity studies, however there were no findings in the repeat-dose toxicity studies to indicate any vaccine-related changes to the tissues of the male reproductive tract.
6. PHARMACEUTICAL PARTICULARS6.1 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 medicinal 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.
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6.5 Nature and contents of the container
One pack of 20 multidose vials (type I glass) of 5 ml suspension (10 × 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.
After shaking, the vaccine is an off-white, opalescent, translucent suspension.
Prior to administration, visually inspect the suspension for any foreign particulate matter and/or abnormal physical appearance. In the event of either being observed, discard the vaccine.
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.
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7. MARKETING AUTHORIZATION HOLDER
Ology Bioservices Ireland LTD
Wilton Park House
Wilton Place
Dublin 2
D02P447
Ireland
8. MARKETING AUTHORISATION NUMBER
EU/1/09/571/001
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION
Date of first authorisation: 16 October 2009