Foclivia

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Foclivia suspension for injection in pre-filled syringe 
Pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain: 
 
A/Vietnam/1194/2004 (H5N1) 7.5 micrograms** 
per 0.5 ml dose 
 
* propagated in fertilised hens’ eggs from healthy chicken flocks 
** expressed in microgram haemagglutinin. 
 
Adjuvant MF59C.1 containing: 
Squalene 9.75 milligrams 
Polysorbate 80 1.175 milligrams 
Sorbitan trioleate 1.175 milligrams 
Sodium citrate 0.66 milligrams 
Citric acid 0.04 milligrams 
 
This vaccine complies with the WHO recommendations and EU decision for the pandemic. 
 
Excipient with known effect: 
The vaccine contains 1.899 milligrams of sodium and 0.081 milligrams of potassium per 0.5 ml dose.  
 
Foclivia may contain trace residues of egg and chicken proteins, ovalbumin, kanamycin sulphate, 
neomycin sulphate, formaldehyde and cetyltrimethylammonium bromide which are used during the 
manufacturing process (see section 4.3). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in pre-filled syringe. 
Milky-white liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Prophylaxis of influenza in an officially declared pandemic situation. 
Foclivia should be used in accordance with Official Guidance. 
 
4.2 Posology and method of administration 
 
Posology 
Adults and elderly (18 years of age and above): 0.5 ml at an elected date. 
A second dose of vaccine should be given after an interval of at least 3 weeks. 
 
Foclivia was evaluated in adults (aged 18 to 60 years old) and elderly (over 60 years old) following 
a 1, 22 day primary vaccination schedule. 
 



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Data on a third dose (booster) administered 6 months after the first dose are limited 
(see sections 4.8 and 5.1). 
 
Paediatric population 
The safety and efficacy of Foclivia in subjects under 18 years of age have not yet been established. 
Currently available data in subjects aged 6 months to 18 years of age are described in section 5.1 but 
no recommendation on a posology can be made. 
 
No data are available in children aged less than 6 months. 
 
Method of administration 
Immunisation should be carried out by intramuscular injection into the deltoid muscle or anterolateral 
thigh (depending on the muscle mass). 
 
4.3 Contraindications 
 
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues 
(eggs, chicken proteins, ovalbumin, kanamycin sulphate, neomycin sulphate, formaldehyde and 
cetyltrimethylammonium bromide) of this vaccine. 
 
However, in a pandemic situation, it may be appropriate to give this vaccine to individuals with a 
history of anaphylaxis as defined above, provided that facilities for resuscitation are immediately 
available in case of need. See section 4.4. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Caution is needed when administrating this vaccine to persons with a known hypersensitivity to the 
active substance, to any of the excipients listed in section 6.1 and to residues (eggs, chicken proteins, 
ovalbumin, kanamycin sulphate, neomycin sulphate, formaldehyde and cetyltrimethylammonium 
bromide). 
 
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 should be postponed in patients with febrile illness 
until the fever is resolved. 
 
The vaccine should under no circumstances be administered intravascularly or intradermally. There 
are no data with Foclivia using the subcutaneous route of administration. 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 bleeding. 
 
Protection against influenza 
There is no immune correlate of protection established for influenza A (H5N1).  
A protective immune response may not be elicited in all vaccine recipients. In addition, antibody 
responses in patients with endogenous or iatrogenic immunosuppression may be insufficient to 
provide protection. 
 
Some degree of cross-reactive immunity has been observed against H5N1 viruses of clades different to 
that of the vaccine strain. However, the degree of protection that may be elicited to H5N1 strains of 
other clades is unknown (see section 5.1). 
 



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Since a second dose is recommended, it should be noted that there are no safety, immunogenicity or 
efficacy data to support interchangeability of Foclivia with other H5N1 monovalent vaccines. 
 
While no data are available from the use of Foclivia, cases of convulsion with and without fever have 
been reported in subjects vaccinated with Focetria, an MF59.1 adjuvanted H1N1 pandemic vaccine 
similar to Foclivia. 
 
The majority of febrile convulsions occurred in paediatric subjects. Some cases were observed in 
subjects with a history of epilepsy. Particular attention should be given to subjects suffering from 
epilepsy and the physician should inform the subjects (or parents) about the possibility to experience 
convulsion. (see section 4.8). 
 
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response 
to the needle injection. This can be accompanied by several neurological signs such as transient visual 
disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that 
procedures are in place to avoid injury from faints. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Foclivia may be co-administered with non-adjuvanted seasonal influenza vaccines, and immunisation 
should be carried out on separate limbs. 
 
There are no data on co-administration of Foclivia with vaccines other than non-adjuvanted seasonal 
influenza vaccines. If co-administration with another vaccine is considered, immunisation should be 
carried out on separate limbs. It should be noted that the adverse reactions may be intensified. 
 
The immunological response may be diminished if the patient is undergoing immunosuppressant treatment. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Limited data obtained from women who became pregnant during the course of clinical trials with 
Foclivia or other pandemic vaccines adjuvanted with MF59C.1 were insufficient to inform vaccine-
associated risks in pregnancy. 
 
However, it is estimated that during the 2009 H1N1 pandemic more than 90,000 women were 
vaccinated during pregnancy with Focetria (an H1N1 pandemic vaccine similar to Foclivia) which 
contains the same amount of MF59C.1 as Foclivia. Post-marketing spontaneously reported adverse 
events and an interventional study do not suggest direct or indirect harmful effects of Focetria 
exposure on pregnancy. In addition, two large observational studies designed to assess the safety of 
Focetria exposure in pregnancy showed no increase in the rates of gestational diabetes, preeclampsia, 
abortions, stillbirth, low birth weight, prematurity, neonatal deaths, and congenital malformations 
among almost 10,000 vaccinated pregnant women and their offspring compared with unvaccinated 
controls. 
 
Health care providers need to assess the benefits and potential risks of administering Foclivia vaccine 
to pregnant women, taking into consideration official recommendations. 
 
Breast-feeding 
There are no data regarding the use of Foclivia during breast-feeding. The potential benefits and risks 
to the mother and infant should be considered before administering Foclivia. 
 
Fertility 
There are no data concerning human fertility. A study in female rabbits did not indicate reproductive 
or developmental toxicity of Foclivia. Male fertility has not been assessed in animals (see section 5.3). 
 



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4.7 Effects on ability to drive and use machines 
 
Some of the effects mentioned under section 4.8 may affect the ability to drive or use machines. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
• Clinical trials 
 
Adverse reactions from clinical trial in adults and elderly (above 18 years old) 
The incidence of adverse reactions has been evaluated in seven clinical trials in healthy subjects 
involving over 4300 adults and elderly receiving H5N1 vaccine combined with MF59C.1 adjuvant (at 
least 7.5 µg haemagglutinin, HA) containing either the A/turkey/Turkey/1/2005 or the 
A/Vietnam/1194/2004 strain. There were 3872 subjects 18-60 years of age, 365 subjects 61-70 years 
of age, and 89 subjects greater than 70 years of age. The safety profile across clinical trials using 
H5N1 vaccine containing either the A/turkey/Turkey/1/2005 or the A/Vietnam/1194/2004 strain is 
comparable (see section 5.1). Clinical trials in 80 subjects receiving adjuvanted vaccine with an H5N3 
or an H9N2 strain showed a similar safety profile. 
 
Across all trials, there was a general trend towards decreased reports of solicited local adverse 
reactions after the second vaccination compared with the first.  
 
Irrespective of antigen dose, almost all solicited systemic adverse reactions were reported on the day 
of vaccination (day 1) or during the 3 days immediately following. 
 
Data on safety of a booster dose are limited to three trials performed with H5N1 MF59C.1 adjuvanted 
vaccine containing A/Vietnam/1194/2004 (V87P1, V87P2) or A/turkey/Turkey/1/2005 (V87P1E1) 
that included 116 adults (18-60 years) and 56 elderly subjects (≥61 years). No increase in solicited 
adverse reactions was reported when a booster dose was administered 6 or 18 months after the initial 
dosing series. A slight increase in solicited adverse reactions in adults was reported when a booster 
dose was administered 18 months after the initial dosing series. In the elderly, the reported solicited 
adverse reactions increased with the third booster dose only when compared with the second dose. 
 
Tabulated list of adverse reactions 
 
The adverse reaction rates reported after any vaccination dose (i.e. 1st, 2nd or booster) were similar 
and are listed according to the following MedDRA frequency convention and system organ class: 
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). 
 

MedDRA System 
Organ class 

Very common 
(≥1/10) 

Common 
(≥1/100 to <1/10) 

Rare 
(≥1/10,000 to 
˂1/1,000) 

Nervous system 
disorders 

Headache   

Gastrointestinal 
disorders 

 Nausea  

Skin and 
subcutaneous tissue 
disorders 

 Sweating  

Musculoskeletal 
and connective 
tissue disorders 

Myalgia Arthralgia  



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General disorders 
and administration 
site conditions 

Injection site 
swelling, Injection 
site pain, Injection 
site induration, 
Injection site redness, 
Fatigue, Chills, 
Malaise 

Injection site 
ecchymosis, Fever  

Anaphylaxis 

 
The majority of these reactions usually disappear within 1-2 days without treatment. 
 
Clinical trials in special populations 
 
Adverse reactions in special populations have been evaluated in two clinical trials, V87_25 and 
V87_26, involving adult (18-60 years) and elderly (≥ 61 years) subjects who were either healthy or 
with underlying medical conditions or immunosuppressive conditions. 
 
 H5N1 MF59C.1 adjuvanted A/turkey/Turkey/1/2005 vaccine 
 Study V87_25 Study V87_26 
 Medical conditions Healthy Immunocompromi

sed Healthy 

 
Adults 
(20-60 
years)* 

Elderly 
(61-84 
years)* 

Adults 
(19-60 
years)* 

Elderly 
(61-79 
years)* 

Adults 
(20-60 
years)* 

Elderly 
(61-84 
years)* 

Adults 
(18-59 
years)* 

Elderly 
(61-91 
years)*  

No. of 
subjects N=145 N=149 N=59 N=58 N=147 N=148 N=58 N=62 

*actual age range of population enrolled 
 
Across studies V87_25 and V87_26, the safety of H5N1 A/turkey/Turkey/1/2005 in healthy adult and 
elderly subjects was consistent with existing safety data from previous clinical trials. However, in 
immunocompromised subjects 18 through 60 years of age, slightly higher rates of nausea (13.0%) 
were reported. In addition, higher rates of arthralgia (up to 23.3%) were reported in both adult and 
elderly subjects, who were immunocompromised or with underlying medical conditions. 
 
The following solicited adverse reactions were additionally collected in these two studies and reported 
with the following frequencies across subjects who received H5N1 A/turkey/Turkey/1/2005 
irrespective of age or health status: diarrhoea (up to 11.9%), loss of appetite (up to 10.9%) and 
vomiting (up to 1.7%). In both studies, subjects with underlying medical and immunosuppressive 
conditions reported higher frequencies of diarrhoea, loss of appetite and vomiting compared to healthy 
subjects (irrespective of age). 
 
Adverse reactions from clinical trial in children aged 6 months to 17 years 
A clinical trial (Study V87P6) was conducted with a H5N1 A/Vietnam/1194/2004 vaccine combined 
with MF59C.1 adjuvant (N=334) vs seasonal influenza vaccine (N=137). 
 
Regardless of age, reactogencity was higher after the first dose than after the second vaccination. 
Reactogenicity after the third dose, administered 12 months following the second dose, was higher 
than after both first and second doses. The percentages of subjects reporting local adverse reactions 
were higher in the older age groups, mainly due to the higher reports for pain. In toddlers, erythema 
and tenderness were the most frequently reported solicited local adverse reactions; irritability and 
unusual crying were the most frequently reported solicited systemic adverse reactions. In children and 
adolescents, pain was the most frequently reported solicited local adverse reaction, and fatigue and 
headache were the most frequently reported solicited systemic adverse reactions. Across all ages, the 
frequency of fever after any dose was not more than 6%.  
 



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 Study V87P6  
H5N1 MF59C.1 adjuvanted A/Vietnam/1194/2004 vaccine  

 First dose Second dose (21 days 
after first dose) 

Third dose (12 months 
after second dose) 

Toddlers (6 to 35  months) N=145 N=138 N=124 
Any 76% 68% 80% 
Local 47% 46% 60% 
Systemic 59% 51% 54% 
Fever ≥ 38°C (≥ 40°C) 0% 0% 0%  
Any Other Adverse Event 54% 49% 35% 

Children (3 to 8 years) N=96 N=93 N=85 
Any 72% 68% 79% 
Local 66% 58% 74% 
Systemic 32% 33% 45% 
Fever ≥ 38°C (≥ 40°C) 4%  2%  6%  
Any Other Adverse Event 36% 31% 19% 
Adolescents(9 to 17 years) N=93 N=91 N=83 
Any 91% 82% 89% 
Local 81% 70% 81% 
Systemic 69% 52% 69% 
Fever ≥ 38°C (≥ 40°C) 0%  1%  2%  
Any Other Adverse Event 30% 27% 22% 

 
Focetria (an MF59.1 adjuvanted H1N1 pandemic vaccine similar to Foclivia). 
 
Adverse reactions in the week following vaccination with Focetria H1N1v from 77 children 3-8 years 
old and 80 children and adolescents 9-17 years old receiving the 7.5 µg formulation were reported 
as follows: 
 

 Injection 1 Injection 2 
Children (3 to 8 years of age) N= 77 N= 75 

Any adverse reaction  74%  69% 
Local  62%  56% 
Systemic  39%  35% 
Fever ≥ 38°C to 38.9°C  4% 1% 
Fever 39°C to 39.9°C 0% 1% 
Fever ≥ 40° C 0% 0% 
Any other AE  14%  17% 

Adolescents (9 to 17 years of age) N= 80 N= 79 
Any adverse reaction  79%  66% 
Local  70%  58% 
Systemic  45%  30% 
Fever ≥ 38°C to 38.9°C  3% 1% 
Fever 39°C to 39.9°C 0% 0% 
Fever ≥ 40° C 0% 0% 
Any other AE  13%  10% 

 
Data in children and adolescents 3-17 years suggest a slight decrease in reactogenicity after the second 
dose, with no increase in rates of fever. 
 
Very common reactions reported in children and adolescents 3 to 17 years of age: 
Pain, induration and erythema, malaise, myalgia, headache and fatigue. 
 



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Adverse reactions in the week following vaccination with Focetria H1N1v from 
73 infants 6-11 months old and 73 toddlers 12-35 months old, receiving the 7.5 µg formulation were 
reported as follows: 
 

 Injection 1 Injection 2 
Infants (6 to 11 months of age) N= 73 N= 68 

Any adverse reaction 79% 65% 
Local 44%  26% 
Systemic  70%  56% 
Fever ≥ 38°C to 38.9°C   11%  9% 
Fever 39°C to 39.9°C  3% 4% 
Fever ≥ 40° C 0% 0% 
Any other AE  32%  31% 

Toddlers (12 to 35 months of age) N= 73 N= 71 
Any adverse reaction 70%  71% 
Local  51%  49% 
Systemic  60%  49% 
Fever ≥ 38°C to 38.9°C  10% 11% 
Fever 39°C to 39.9°C 4% 1% 
Fever ≥ 40° C 1% 0% 
Any other AE 21%  24% 

 
Data in infants and toddlers 6-35 months of age suggest a slight decrease in reactogenicity after the 
second dose, with no increase in rates of fever. 
 
Very common reactions reported in 146 infants and toddlers 6 to 35 months of age: 
Tenderness, erythema, irritability, unusual crying, sleepiness, diarrhoea, vomiting and change in eating 
habits. Induration and ecchymosis were very common reactions in toddlers but were less common in 
infants. 
 
• Post-marketing surveillance 
 
No post-marketing surveillance data are available following Foclivia administration. 
 
The following adverse events were reported from post-marketing surveillance with Focetria (an H1N1 
pandemic vaccine similar to Foclivia) which contains the same amount of adjuvant MF59C.1 as 
Foclivia, approved for use in children 6 months of age and above, adults and the elderly: 
 
Blood and lymphatic system disorders 
Lymphadenopathy. 
 
Immune system disorders 
Allergic reactions, anaphylaxis including dyspnoea, bronchospasm, laryngeal oedema, in rare cases 
leading to shock, angioedema. 
 
Nervous system disorders 
Headache, dizziness, somnolence, syncope. Neurological disorders, such as neuralgia, paraesthesia, 
convulsions and neuritis. 
 
Cardiac disorders 
Palpitation, tachycardia. 
 
Respiratory disorders 
Cough. 



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Gastrointestinal disorders 
Gastrointestinal disorders such as nausea, vomiting, abdominal pain and diarrhoea.  
 
Skin and subcutaneous tissue disorders 
Generalised skin reactions including pruritus, urticaria or non-specific rash. 
 
Musculoskeletal, connective tissue and bone disorders 
Muscular weakness, pain in extremities. 
 
General disorders and administration site conditions 
Asthenia. 
 
The following additional adverse events were reported from post-marketing surveillance with seasonal 
non-adjuvanted trivalent vaccines in all age groups and a seasonal trivalent MF59-adjuvanted subunit 
influenza vaccine approved for use in elderly subjects 65 years of age and older: 
 
Blood and lymphatic system disorders 
Thrombocytopenia (in some cases reversible platelet counts less than 5000 mm3). 
 
Nervous system disorders 
Neurological disorders, such as encephalomyelitis  and Guillain Barré syndrome. 
 
Vascular disorders 
Vasculitis which may be associated with transient renal involvement. 
 
Skin and subcutaneous tissue disorders 
Erythema multiforme. 
 
General disorders and administration site conditions 
Extensive swelling of injected limb lasting more than one week, injection-site cellulitis-like reaction 
(some cases of swelling, pain, and redness extending more than 10 cm and lasting more than 1 week). 
 
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 Appendix V 
 
4.9 Overdose 
 
No case of overdose has been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02 
 
Clinical efficacy and safety 
 
Pandemic preparedness 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 a pandemic preparedness vaccine will support a vaccination strategy that is likely to be 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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used for the pandemic vaccine: clinical efficacy and safety data obtained with pandemic preparedness 
vaccines are relevant for the pandemic vaccines. 
 
Immune response to H5N1 vaccine combined with MF59C.1 adjuvant containing 
A/Vietnam/1194/2004 or A/turkey/Turkey/1/2005 strain. 
 
Adults (18-60 years) 
 
A Phase II clinical trial (V87P1) was conducted with H5N1  MF59C.1 adjuvanted vaccine containing 
A/Vietnam/1194/2004 in 312 healthy adults. Two doses of vaccine containing 7.5 µg 
Haemagglutinin(HA)/dose were administered three weeks apart to 156 subjects. Immunogenicity was 
assessed in 149 subjects. 
 
In a phase III clinical trial (V87P13), 2693  adult subjects were enrolled and 2566 received two doses of 
H5N1 MF59C.1 adjuvanted vaccine containing A/Vietnam/1194/2004 7.5 µg HA/dose administered 
three weeks apart. Immunogenicity was assessed in a subset (N=197) of subjects. 
 
In a third clinical trial (V87P11) 194 adult subjects received two doses of H5N1 MF59C.1 adjuvanted 
vaccine containing A/turkey/Turkey/1/2005 7.5 µg HA/dose administered three weeks apart. 
Immunogenicity was assessed in 182 subjects. 
 
The seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA 
antibody to H5N1 A/Vietnam/1194/2004 and to H5N1 A/turkey/Turkey/1/2005 in the adults measured 
by Single Radial Haemolysis (SRH) assay was as follows: 
 

Anti-HA antibody 
(SRH) 

Study V87P1 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=149 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=197 

Study V87P11 
A/turkey/Turkey/1/2005 

21 days after 2nd dose 
N=182 

Seroprotection rate 
(95%CI)* 

85% (79-91) 91% (87-95) 91% (85-94) 

Seroconversion rate 
(95%CI)** 

85% (78-90) 78% (72-84) 85% (79-90) 

Seroconversion factor 
(95%CI)*** 

7.74 (6.6-9.07) 4.03 (3.54-4.59) 6 (5.2-6.93) 

 

Anti-HA antibody (SRH) 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=69 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=128 

- 

Baseline Serostatus < 4 mm2 ≥ 4 mm2 - 
Seroprotection rate 
(95%CI)* 

87% (77-94) 94% (88-97) - 

Seroconversion rate 
(95%CI)** 

87% (77-94) 73% (65-81) - 

Seroconversion factor 
(95%CI)*** 

8.87 (7.09-11) 2.71 (2.38-3.08) - 

* Seroprotection: SRH area ≥25 mm2 
** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 

area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** geometric mean ratios (GMRs) of SRH 
 
MicroNeutralization (MN) results against A/Vietnam/1194/2004 (Studies V87P1 and V87P13) 
indicate a seroprotection and seroconversion rate ranging from 67% (60-74) to 85% (78-90) and 65% 
(58-72) to 83% (77-89), respectively. Immune response to vaccination assessed by MN assay is in line 
with results obtained with SRH. 
 



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In Study V87P11 MN results against homologous A/turkey/Turkey/1/2005 indicate a seroprotection 
and seroconversion rate of 85% (79-90) and 93% (89-96), respectively. Immune response to 
vaccination assessed by MN assay is in line with results obtained with SRH. 
 
Persistence of antibodies after primary vaccination in this population was assessed by 
Hemagglutination Inhibition (HI), SRH, and MN assays. Compared to the antibody levels obtained at 
day 43 after completion of primary vaccination schedules, antibody levels at day 202 were reduced 
by 1/5 to 1/2 from their prior levels. 
 
Elderly (≥61 years) 
 
The seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA 
antibody to H5N1 MF59C.1 adjuvanted vaccine (A/Vietnam/1194/2004 and A/turkey/Turkey/1/2005) 
in subjects aged 61 years and older (limited number of subjects were above 70 years of age; N=123) 
measured by SRH assay assessed in two clinical studies were as follows: 
 

Anti-HA antibody 
(SRH) 

Study V87P1 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=84a 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=210b 

Study V87P11 
A/turkey/Turkey/1/2005 

21 days after 2nd dose 
N=132c 

Seroprotection rate 
(95%CI)* 

80% (70-88) 82% (76-87) 82% (74-88) 

Seroconversion rate 
(95%CI)** 

70% (59-80) 63% (56-69) 70% (61-77) 

Seroconversion factor 
(95%CI)*** 

4.96 (3.87-6.37) 2.9 (2.53-3.31) 3.97 (3.36-4.69) 

 

Anti-HA antibody (SRH) 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=66 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=143 
Baseline Serostatus < 4 mm2 ≥ 4 mm2 
Seroprotection rate (95%CI)* 82% (70-90) 82% (75-88) 
Seroconversion rate (95%CI)** 82% (70-90) 54% (45-62) 
Seroconversion factor (95%CI)*** 8.58 (6.57-11) 1.91 (1.72-2.12) 

a  Ages 62-88 years; b Ages 61-68 years; c Ages 61-89 years 
* Seroprotection: SRH area ≥25 mm2 
** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 

area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
 
MN results against A/Vietnam/1194/2004 (Studies V87P1 and V87P13) indicate a seroprotection and 
seroconversion rate ranging from 57% (50-64) to 79% (68-87) and 55% (48-62) to 58% (47-69) 
respectively. MN results, similar to SRH results, demonstrated strong immune response after 
completion of priming vaccination series in a population of elderly subjects. 
 
In Study V87P11, MN results against homologous A/turkey/Turkey/1/2005 indicate a seroprotection 
and seroconversion rate of 68% (59-75) and 81% (74-87), respectively. Immune response to 
vaccination assessed by MN assay is similar to SRH results. 
 
Persistence of antibodies after primary vaccination in this population as assessed by HI, SRH, and MN 
tests reduced from 1/2 to 1/5 of their post-vaccination level at day 202 as compared to day 43 after 
completion of primary schedules as assessed by HI, SRH, and MN tests. Up to 50% (N=33) of the 
elderly subjects aged 62 to 88 years immunised with H5N1 MF59C.1 adjuvanted vaccine containing 
A/Vietnam/1194/2004 in trial V87P1 were seroprotected at six months. 



12 

 
A third (booster) dose of H5N1 vaccine combined with MF59C.1 was administered 6 months after the 
primary vaccination series. Results are shown by SRH. 
 
The seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA 
antibody to H5N1 A/Vietnam/1194/2004 measured by SRH assays were as follows: 
 

 Study V87P1 Adults 
A/Vietnam/1194/2004 
booster after 2nd dose 

Study V87P2 Adults 
A/Vietnam/1194/2004 
booster after 2nd dose 

Study V87P1 Elderly 
A/Vietnam/1194/2004 
booster after 2nd dose 

SRH N=71 N=13 N=38 
Seroprotection rate 
(95%CI)* 

89% (79-95) 85% (55-98) 84% (69-94) 

Seroconversion rate 
(95%CI)** 

83% (72-91) 69% (39-91) 63% (46-78) 

Seroconversion factor 
(95%CI)*** 

5.96 (4.72-7.53) 2.49 (1.56-3.98) 5.15 (3.46-7.66) 

* Seroprotection: SRH area ≥25 mm2 
** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 

area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
 
• Supportive data in adult and elderly populations 
 
In two dose finding studies 80 adults received an adjuvanted pandemic preparedness vaccine (H5N3 or 
H9N2). Two doses of vaccine with H5N3 (A/Duck/Singapore/97) strain at 3 different dosages 
(7.5, 15 and 30 µg HA/dose) were administered three weeks apart. 
 
Serum samples were tested against the original H5N3 and also a number of H5N1 isolates. 
 
Serologic responses obtained with the SRH assay showed that 100% of subjects achieved 
seroprotection and 100% seroconverted after two 7.5 µg injections. The adjuvanted vaccine was also 
found to induce antibodies that cross-protected against the H5N1 strains isolated in 2003 and 2004, 
which exhibit some antigenic drift compared to the original strains. 
 
Two doses of vaccine containing H9N2 (A/chicken/Hong Kong/G9/97) strain at 4 different dosages 
(3.75, 7.5, 15 and 30 µg HA/dose), were administered four weeks apart. Serologic responses obtained 
with the HI assay showed that 92% of subjects achieved seroprotection and 75% seroconverted after 
two 7.5 µg injections. 
 
Cross reactivity 
 

Cross-reactive immune response elicited by H5N1 A/Vietnam/1194/2004 against 
A/turkey/Turkey/1/2005 and A/Indonesia/5/2005 

 
Adults (18-60 years) 
 
Some heterologous immune response against A/turkey/Turkey/1/2005 (NIBRG23; clade 2.2.1) and 
A/Indonesia/5/2005 (clade 2.1) was detectable both after the second and third vaccinations, indicating 
cross-reactivity of the clade 1 vaccine against clade 2 strains. 
 



13 

Seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA antibodies 
to H5N1 A/turkey/Turkey/1/2005 after the 2nd dose in adults 18-60 years of age, measured by SRH 
and HI assays were as follows: 
 

 Anti-HA 
antibody 

Study V87P1 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose  
N=70 

Study V87P12 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose 
N=60 

Study V87P3 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose 
N=30 

Study V87P13 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose 
N=197 

SR
H 

Seroprotectio
n rate 
(95%CI)* 

70% (58-80) 65% (52-77) 90% (73-98) 59% (52-66) 

Seroconversio
n rate 
(95%CI)** 

NAǂ 65% (52-77) 86% (68-96) 49% (42-56) 

Seroconversio
n 
factor(95%CI)
*** 

NAǂ 4.51 (3.63-5.61) 7.67 (6.09-9.67) 2.37 (2.1-2.67) 

  N=69 N=60 N=30 N=197 
HI Seroprotectio

n rate 
(95%CI)° 

36% (25-49) 28% (17-41) 24% (10-44) 23% (18-30) 

Seroconversio
n rate 
(95%CI)° 

NAǂ 28% (17-41) 21% (8-40) 19% (14-25) 

Seroconversio
n factor 
(95%CI)°° 

NAǂ 2.3 (1.67-3.16) 1.98 (1.22-3.21) 1.92 (1.64-2.25) 

* Seroprotection: SRH area ≥25 mm2 

** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 
area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
ǂ In V87P1: baseline not tested 
° measured by HI assay ≥40 
°° GMRs of HI 
 
MN results for the clinical studies V87P12, V87P3 and V87P13 in the Table above revealed a 
seroprotection rate and seroconversion rate against A/turkey/Turkey/2005 ranging from 10% (2-27) 
to 39% (32-46) and 10% (2-27) to 36% (29-43) respectively. MN results yielded a GMR against 
A/turkey/Turkey/2005 ranging from 1.59 to 2.95. 
 
Elderly (≥61 years) 
 
Seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibodies 
to H5N1 A/turkey/Turkey/05 after the 2nd dose in elderly subjects ≥61 years of age, measured by SRH 
and HI assays were as follows: 
 

 Anti-HA antibody 

Study V87P1 
A/Vietnam/1194/2004 
 
21 days after 2nd dose 
N=37 

Study V87P13 
A/Vietnam/1194/2004 
 
21 days after 2nd dose 
N=207 

SRH Seroprotection rate (95%CI)* 57% (39-73) 20% (18-23) 
Seroconversion rate (95%CI)* NA*** 48% (41-55) 



14 

Seroconversion factor (95%CI)** NA*** 1.74 (1.57-1.94) 
  N=36 N=208 

HI 
Seroprotection rate (95%CI)° 36% (21-54) 25% (19-32) 
Seroconversion rate (95%CI)° NA*** 19% (14-25) 
Seroconversion factor (95%CI)°° NA*** 1.79 (1.56-2.06) 

* measured by SRH assay ≥25 mm2 
** geometric mean ratios of SRH 
° measured by HI assay ≥40 
°° geometric mean ratios of HI 
*** In V87P1: baseline not tested 
 
MN results for the clinical studies in the Table above revealed a seroprotection rate against 
A/turkey/Turkey/05 ranging from 11% (3-25) (study V87P1) to 30% (24-37) (study V87P13) and 
seroconversion rate of 25% (19-31) for study V87P13. MN results in study V87P13 yielded a GMR 
against A/turkey/Turkey/05 of 2.01 (1.78-2.26). 
 

Cross-reactive immune response elicited by A/turkey/Turkey/1/2005 against 
A/Indonesia/5/2005 and A/Vietnam/1194/2004 

 
Heterologous immune response against A/Indonesia/5/2005 (clade 2.1) was detectable in Study 
V87P11 after the second vaccination, indicating cross-reactivity of the clade 2.2.1 vaccine against 
clade 2.1 strains. 
 
Seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA antibodies 
to H5N1 A/Indonesia/5/2005 and A/Vietnam/1194/2004 after the 2nd dose in adults (18-60 years) and 
elderly (> 61years), measured by SRH and HI assays were as follows: 
 

Anti-HA 
antibody 

 V87P11 Adults (18-60 years) 
N=186 

V87P11 Elderly (>61-89 years)a 
N=142 

  A/Indonesia/ 
5/2005 

A/Vietnam/ 
1194/2004 

A/Indonesia/ 
5/2005 

A/Vietnam/ 
1194/2004 

SRH Seroprotection 
rate (95%CI)* 

83 
(77-88) 

62 
(54-69) 

61 
(52-69) 

45 
(37-54) 

 Seroconversion 
rate (95%CI)** 

79 
(72-85) 

60 
(53-68) 

64 
(56-73) 

44 
(35-53) 

 Seroconversion 
factor 
(95%CI)*** 

6.24 
(5.44-7.16) 

4.45 
(3.85-5.14) 

3.87 
(3.31-4.53) 

3.03 
(2.56-3.58) 

  N=194 N=148 
HI Seroprotection 

rate (95%CI) ° 
50 

(43-57) 
47 

(40-55) 
34 

(26-42) 
39 

(31-48) 
 Seroconversion 

rate (95%CI) ° 
49 

(42-56) 
44 

(37-51) 
32 

(25-41) 
34 

(26-42) 
 Seroconversion 

factor (95%CI) °° 
4.71 

(3.74-5.93) 
4.25 

(3.36-5.37) 
2.69 

(2.18-3.32) 
2.8 

(2.2-3.55) 
a  actual age range of population enrolled 
* Seroprotection: SRH area ≥25 mm2 

** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 
area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
° measured by HI assay ≥40 
°° GMRs of HI 
 
MN results for A/Indonesia/5/2005 revealed a seroprotection rate of 38% (31-45) in adults 
(18-60 years) and 14% (8-20) in elderly (>61 years); a seroconversion rate of 58% (50-65) in adults 
and 30% (23-38) in elderly and finally a GMR of 4.67 (3.95-5.56) in adults and 2.19 (1.86-2.58) 
in elderly. 



15 

 
MN results for A/Vietnam/1194/2004 revealed a seroprotection rate of 10% (6-16) in adults 
(18-60 years) and 6% (3-11) in elderly (>61 years); a seroconversion rate of 19% (13-25) in adults 
and 7% (4-13) in elderly and finally a GMR of 1.86 (1.63-2.12) in adults and 1.33 (1.17-1.51) 
in elderly. 
 
Long term booster immune memory: 
 
A single vaccination with H5N1 MF59C.1 adjuvanted A/Vietnam/1194/2004 vaccine induced high 
and rapid serological response in subjects primed 6-8 years previously with two doses of a different 
vaccine, having the same formulation but using the H5N3 strain. 
 
In a phase I clinical trial (V87P3) adult subjects aged 18-65 years primed 6-8 years previously with 2 
doses of MF59-adjuvanted H5N3 vaccine/A/Duck/Singapore/97, were administered 2 booster doses of  
H5N1 MF59C.1 adjuvanted A/Vietnam/1194/2004 vaccine. SRH results after the first dose, that 
mimic prepandemic priming plus single heterologous booster dose, revealed seroprotection and 
seroconversion rates of 100% (74- 100) and an 18-fold increase in SRH area (GMR).   
 
Alternative vaccination schedules: 
 
In a clinical trial evaluating 4 different vaccination schedules in 240 subjects 18 to 60 years of age, 
where the second dose occurred either 1, 2, 3 or 6 weeks after the first dose of H5N1 MF59C.1 
adjuvanted A/Vietnam/1194/2004 vaccine, all vaccine schedule groups after 3 weeks from the 2nd 
vaccination achieved high levels of antibodies as evaluated with SRH. SRH seroprotection rates 
ranged from 86% to 98%, seroconversion rates from 64% to 90%, and GMR ranged from 2.92 to 4.57. 
The magnitude of immune response was lower in the group who received the 2nd dose 1 week later and 
higher in the groups with longer interval schedules. 
 
Subjects with underlying medical or immunosuppressive conditions: 
 
Immunogenicity of H5N1 A/turkey/Turkey/1/2005 in adults (18 to 60 years) and elderly (>61 years) 
subjects with underlying medical conditions (Study V87_25) or immunosuppressive conditions 
(mainly HIV-infected subjects) (Study V87_26) in comparison to healthy adults (18-60 years) and 
elderly (>61 years), was evaluated in two randomised, phase III controlled clinical trials (with a 
seasonal trivalent inactivated MF59-adjuvanted subunit influenza vaccine approved for use in elderly 
subjects 65 years of age and older as a comparator). In trial V87_25 and V87_26, 96 and 67 subjects, 
respectively, were over the age of 70 years. In both trials, immunogenicity of 
H5N1 A/turkey/Turkey/1/2005 was shown by HI, SRH and MN assays following both the first and 
second dose.  
 
Geometric mean area*, seroprotection rate*, seroconversion rate* and the seroconversion factor** for 
anti-HA antibody to H5N1 A/turkey/Turkey/1/2005 measured by SRH assays 21 days after the 2nd 
dose were as follows: 

Study V87_25 

 
Adults 

 (20- 60 years)a  
Adults  

(19- 60 years)a 
Elderly  

(61-84 years)a 
 

Elderly 
(61-79 years)a 

 

Anti-HA antibody 
(SRH) 

Medical 
Conditions 

N=140 

Healthy 
N=57 

Medical 
Conditions 

N=143 

Healthy 
N=57 

Geometric Mean 
Area (95%CI)* 

31.07 
(27.43-35.19) 

58.02 
(48.74-69.06) 

29.34 
(26.07-33.01) 

27.78 
(22.57-34.18) 

Seroprotection rate 
(95%CI)* 

65.00 
(56.5-72.9) 

89.47 
(78.5-96) 

58.74 
(50.2-66.9) 

57.89 
(44.1-70.9) 

Seroconversion rate 
(95%CI)* 

72.86 
(64.7-80) 

98.25 
(90.6-99.96) 

64.34 
(55.9-72.2) 

66.67 
(52.9-78.6) 



16 

a  actual age range of population enrolled 
*  measured by SRH assay seroprotection: SRH area ≥25 mm2, seroconversion: SRH area ≥25 mm2 for subjects with a 

baseline SRH area ≤4 mm2 or a minimum 50% increase in SRH area for subjects with >4 mm2. 
** geometric mean ratios of SRH 

 
HI results for the two clinical studies revealed lower values than those reported in previous studies. 
Seroconversion rates against homologous A/turkey/Turkey/1/2005 ranged from 37.50% to 43.10% in 
healthy adults, and from 19.18% to 26.47% in adults with immunosuppressive or underlying medical 
conditions, respectively; seroconversion rates ranged from 21.43% to 30.65% in healthy elderly 
subjects, and from 24.49% to 27.86% in elderly subjects with immunosuppressive or underlying 
medical conditions. Similar trends were observed for seroprotection rates in both studies. 
 
MN results against homologous A/turkey/Turkey/1/2005 indicate a seroconversion rate of 66.67% in 
healthy adults, and ranging from 33.57% to 54.14% in adults with immunosuppressive or underlying 
medical conditions, respectively; seroconversion rates ranged from 24.39% to 29.03% in healthy 
elderly subjects, and from 31.65% to 39.42% in elderly subjects with immunosuppressive or 
underlying medical conditions. Similar trends were observed for seroprotection rates in both studies. 
 
In both studies V87_25 and V87_26, the lower levels of antibodies (as measured by HI, SRH and MN 
assays) and reduced seroprotection rates in adults and elderly (≥ 61 years old) subjects with underlying 
medical or immunosuppressive conditions, suggest that H5N1 A/turkey/Turkey/1/2005 may not elicit 
the same level of protection against A/H5N1 strain as compared to healthy adults (see section 4.4). 
These studies provided limited immunogenicity data in subjects with some underlying medical (in 
particular, renal impairment and peripheral cardiovascular disease) and immunosuppressive conditions 
(in particular, transplant recipients and patients under cancer treatment). In these trials, lower levels of 
antibodies and reduced seroprotection rates against homologous H5N1 A/turkey/Turkey/1/2005 were 
also measured in healthy elderly subjects, as compared to healthy adults, though previous studies 
showed induction of sufficiently immunogenic responses against H5N1 strains (see above for 
information on elderly). 
 

Available data in paediatric populations 
 
A clinical trial (V87P6) was conducted with a H5N1 A/Vietnam/1194/2004 vaccine combined with 
MF59C.1 adjuvant in 471 children from 6 months to 17 years of age. Two doses of 7.5 µg were 
administered three weeks apart and a third dose 12 months following the first dose. After 3 weeks 
from the 2nd vaccination (day 43) all age groups (i.e. 6-35 months, 3-8 years and 9-17 years) achieved 
high levels of antibodies to A/Vietnam/1194/2004 as evaluated with SRH and HI assays as presented 
in table below. In this trial no vaccine related SAEs were observed. 

Seroconversion 
factor (95%CI)** 

3.33 
(2.94-3.77) 

6.58 
(5.53-7.83) 

2.37 
(2.10-2.66) 

2.96 
(2.41-3.64) 

Study V87_26 

 
Adults  

(20- 60 years)a   
Adults 

(18-59 years)a 
Elderly  

(61-84 years)a 
 

Elderly  
(61-91 years)a 

 

Anti-HA antibody 
(SRH) 

Immuno- 
compromised 

N=143 

Healthy 
N=57 

Immuno- 
compromised 

N=139 

Healthy 
N=62 

Geometric Mean 
Area (95%CI)* 

26.50 
(22.49-31.22) 

48.58 
(40.01-58.99) 

26.85 
(23.01-31.33) 

23.91 
(18.89-30.26) 

Seroprotection rate 
(95%CI)* 

60.84 
(52.3-68.9) 

87.72 
(76.3-94.9) 

58.99 
(50.3-67.3) 

53.23 
(40.1-66) 

Seroconversion rate 
(95%CI)* 

61.54 
(53-69.5) 

89.47 
(78.5-96) 

64.75 
(56.2-72.7) 

56.45 
(43.3-69) 

Seroconversion 
factor (95%CI)** 

3.16 
(2.69-3.73) 

7.10 
(5.85-8.62) 

3.15 
(2.70-3.68) 

2.83 
(2.24-3.58) 



17 

 
 Toddlers (6 to 

35 months) 
Children  

(3 to 8 years) 
Adolescents (9 to 

17 years) 
N=134 N=91 N=89 

HI 

Seroprotection rate 
(95% CI) 
Day 43 

97% 
(92-99) 

97% 
(91-99) 

89% 
(80-94) 

Seroconversion 
factor (95% CI) 
Day 43 to Day 1 

129 
(109-151) 

117 
(97-142) 

67 
(51-88) 

Seroconversion 
rate (95% CI) 

Day 43 

97% 
(92-99) 

97% 
(91-99) 

89% 
(80-94) 

SRH 

 N=133 N=91 N=90 
Seroprotection rate 

(95% CI) 
Day 43 

100% 
(97-100) 

100% 
(96-100) 

100% 
(96-100) 

Seroconversion 
factor (95% CI) 
Day 43 to Day 1 

16 
(14-18) 

15 
(13-17) 

14 
(12-16) 

Seroconversion 
rate (95% CI) 

Day 43 

98% 
(95-100) 

100% 
(96-100) 

99% 
(94-100) 

  
MN results against a A/Vietnam/1194/2004 indicate a seroprotection rate of 99% (95%CI: 94-100), 
a seroconversion rate ranging from 97% (95%CI: 91-99) to 99% (95%CI: 96-100) and a GMR ranging 
from 29 (95%CI: 25-35) to 50 (95%CI: 44-58). 
 
Immunogenicity results with Focetria H1N1v (Study V111_03): 
The seroprotection rate and seroconversion rate measured by HI assay and the seroconversion factor 
expressed as geometric mean ratio of HI for anti-HA antibody to H1N1 after administration of one and 
two 7.5 µg doses of Focetria was evaluated in 70 children and adolescents (9-17 years), 60 children 
(3-8 years), 58 children (12-35 months) and 49 infants (6-11 months). CHMP immunogenicity criteria 
set for adults (18-60 years) were met both after the 1st and the 2nd dose in all the above age strata (both 
in the overall population and in the subset seronegative at baseline). 
 
The European medicines Agency has deferred the obligation to submit the results of studies with 
Foclivia in one or more subsets of the paediatric populations in active immunisation against 
H5N1 subtype of Influenza A virus. See section 4.2 for information on paediatric use. 
 
Foclivia 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. 
 
5.2 Pharmacokinetic properties 
 
Not applicable. 
 
5.3 Preclinical safety data 
 
Non-clinical data obtained with Foclivia and with seasonal influenza vaccine containing 
MF59C.1 adjuvant reveal no special hazard for humans based on conventional studies of repeated 
dose toxicity, local tolerance, female fertility, and reproductive and developmental toxicity (through 
the end of the lactation period). 
 
 



18 

6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride, 
Potassium chloride, 
Potassium dihydrogen phosphate, 
Disodium phosphate dihydrate, 
Magnesium chloride hexahydrate, 
Calcium chloride dihydrate, 
 
Water for injections. 
 
For the adjuvant, see section 2. 
 
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. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. Discard if the vaccine has been frozen. Store in the 
original package in order to protect from light. 
 
6.5 Nature and contents of container 
 
0.5 ml in pre-filled syringe (type I glass) with plunger-stopper (bromo-butyl rubber). Packs of 1 and 10 
with or without needle. Syringes without needle are fitted with a Luer Lock system. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Gently shake before use. 
 
After shaking, the normal appearance of Foclivia is a milky-white suspension. 
 
Visually inspect the suspension prior to administration. In case of any particles and/or abnormal 
appearance, the vaccine should be discarded. 
 
When using a pre-filled syringe without needle supplied with a Luer Lock system, remove the tip cap 
by unscrewing it in a counter-clockwise direction. Once the tip cap is removed, attach a needle to the 
syringe by screwing it on in a clockwise direction until it locks. Once the needle is locked in place, 
remove the needle protector and administer the vaccine. 
 
Any unused vaccine or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Seqirus S.r.l. 
Via del Pozzo 3/A, S. Martino 
53035 Monteriggioni (SI) 



19 

Italy 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/577/001-002 
EU/1/09/577/005-006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 October 2009 
Date of latest renewal: 19 October 2014 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/. 
 

http://www.ema.europa.eu/


20 

1. NAME OF THE MEDICINAL PRODUCT 
 
Foclivia suspension for injection 
Pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain: 
 
A/Vietnam/1194/2004 (H5N1) 7.5 micrograms** 
per 0.5 ml dose 
 
* propagated in fertilised hens’ eggs from healthy chicken flocks 
** expressed in microgram haemagglutinin. 
 
Adjuvant MF59C.1 containing: 
Squalene 9.75 milligrams 
Polysorbate 80 1.175 milligrams 
Sorbitan trioleate 1.175 milligrams 
Sodium citrate 0.66 milligrams 
Citric acid 0.04 milligrams 
 
This vaccine complies with the WHO recommendations and EU decision for the pandemic. 
 
Excipient with known effect: 
The vaccine contains 1.899 milligrams of sodium and 0.081 milligrams of potassium per 0.5 ml dose.  
 
Foclivia may contain trace residues of egg and chicken proteins, ovalbumin, kanamycin sulphate, 
neomycin sulphate, formaldehyde and cetyltrimethylammonium bromide which are used during the 
manufacturing process (see section 4.3). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection. 
Milky-white liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Prophylaxis of influenza in an officially declared pandemic situation. 
Foclivia should be used in accordance with Official Guidance. 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults and elderly (18 years of age and above): 0.5 ml at an elected date. 
A second dose of vaccine should be given after an interval of at least 3 weeks. 
 
Foclivia was evaluated in adults (aged 18 to 60 years old) and elderly (over 60 years old) following 
a 1, 22 day primary vaccination schedule. 



21 

 
Data on a third dose (booster) administered 6 months after the first dose are limited (see 
sections 4.8 and 5.1). 
 
Paediatric population 
The safety and efficacy of Foclivia in subjects under 18 years of age have not yet been established. 
Currently available data in subjects aged 6 months to 18 years of age are described in section 5.1 but 
no recommendation on a posology can be made. 
 
No data are available in children aged less than 6 months. 
 
Method of administration 
Immunisation should be carried out by intramuscular injection into the deltoid muscle or anterolateral 
thigh (depending on the muscle mass). 
 
4.3 Contraindications 
 
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues 
(eggs, chicken proteins, ovalbumin, kanamycin sulphate, neomycin sulphate, formaldehyde and 
cetyltrimethylammonium bromide) of this vaccine. However, in a pandemic situation, it may be 
appropriate to give this vaccine to individuals with a history of anaphylaxis as defined above, provided 
that facilities for resuscitation are immediately available in case of need. See section 4.4. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Caution is needed when administrating this vaccine to persons with a known hypersensitivity to the 
active substance, to any of the excipients listed in section 6.1 and to residues (eggs, chicken proteins, 
ovalbumin, kanamycin sulphate, neomycin sulphate, formaldehyde and cetyltrimethylammonium 
bromide). 
 
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 should be postponed in patients with febrile illness 
until the fever is resolved. 
 
The vaccine should under no circumstances be administered intravascularly or intradermally. There 
are no data with Foclivia using the subcutaneous route of administration. 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 bleeding. 
 
Protection against influenza 
There is no immune correlate of protection established for influenza A (H5N1).  
A protective immune response may not be elicited in all vaccine recipients. In addition, antibody 
responses in patients with endogenous or iatrogenic immunosuppression may be insufficient to 
provide protection. 
 
Some degree of cross-reactive immunity has been observed against H5N1 viruses of clades different to 
that of the vaccine strain. However, the degree of protection that may be elicited to H5N1 strains of 
other clades is unknown (see section 5.1). 
 



22 

Since a second dose is recommended, it should be noted that there are no safety, immunogenicity 
or efficacy data to support interchangeability of Foclivia with other H5N1 monovalent vaccines. 
 
While no data are available from the use of Foclivia, cases of convulsion with and without fever have 
been reported in subjects vaccinated with Focetria, an MF59.1 adjuvanted H1N1 pandemic vaccine 
similar to Foclivia. 
 
The majority of febrile convulsions occurred in paediatric subjects. Some cases were observed in 
subjects with a history of epilepsy. Particular attention should be given to subjects suffering from 
epilepsy and the physician should inform the subjects (or parents) about the possibility to experience 
convulsion. (see section 4.8). 
 
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to 
the needle injection. This can be accompanied by several neurological signs such as transient visual 
disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that 
procedures are in place to avoid injury from faints. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Foclivia may be co-administered with non-adjuvanted seasonal influenza vaccines, and immunisation 
should be carried out on separate limbs. 
 
There are no data on co-administration of Foclivia with vaccines other than non-adjuvanted seasonal 
influenza vaccines. If co-administration with another vaccine is considered, immunisation should be 
carried out on separate limbs. It should be noted that the adverse reactions may be intensified. 
 
The immunological response may be diminished if the patient is undergoing immunosuppressant 
treatment. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Limited data obtained from women who became pregnant during the course of clinical trials with 
Foclivia or other pandemic vaccines adjuvanted with MF59C.1 were insufficient to inform vaccine-
associated risks in pregnancy. 
 
However, it is estimated that during the 2009 H1N1 pandemic more than 90,000 women were 
vaccinated during pregnancy with Focetria (an H1N1 pandemic vaccine similar to Foclivia) which 
contains the same amount of MF59C.1 as Foclivia. Post-marketing spontaneously reported adverse 
events and an interventional study do not suggest direct or indirect harmful effects of Focetria 
exposure on pregnancy. In addition, two large observational studies designed to assess the safety of 
Focetria exposure in pregnancy showed no increase in the rates of gestational diabetes, preeclampsia, 
abortions, stillbirth, low birth weight, prematurity, neonatal deaths, and congenital malformations 
among almost 10,000 vaccinated pregnant women and their offspring compared with unvaccinated 
controls. 
 
Health care providers need to assess the benefits and potential risks of administering Foclivia vaccine 
to pregnant women, taking into consideration official recommendations. 
 
Breast-feeding 
There are no data regarding the use of Foclivia during breast-feeding. The potential benefits and risks 
to the mother and infant should be considered before administering Foclivia. 
 
Fertility 
There are no data concerning human fertility. A study in female rabbits did not indicate reproductive 
or developmental toxicity of Foclivia. Male fertility has not been assessed in animals (see section 5.3). 
 



23 

4.7 Effects on ability to drive and use machines 
 
Some of the effects mentioned under section 4.8  may affect the ability to drive 
or use machines. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
• Clinical trials 
 
Adverse reactions from clinical trial in adults and elderly (above 18 years old) 
The incidence of adverse reactions has been evaluated in seven clinical trials in healthy subjects 
involving over 4300 adults and elderly receiving H5N1 vaccine combined with MF59C.1 adjuvant (at 
least 7.5 µg haemagglutinin, HA) containing either the A/turkey/Turkey/1/2005 or the 
A/Vietnam/1194/2004 strain. There were 3872 subjects 18-60 years of age, 365 subjects 61-70 years 
of age, and 89 subjects greater than 70 years of age. The safety profile across clinical trials using 
H5N1 vaccine containing either the A/turkey/Turkey/1/2005 or the A/Vietnam/1194/2004 strain is 
comparable (see section 5.1). Clinical trials in 80 subjects receiving adjuvanted vaccine with an H5N3 
or an H9N2 strain showed a similar safety profile. 
 
Across all trials, there was a general trend towards decreased reports of solicited local adverse 
reactions after the second vaccination compared with the first.  
 
Irrespective of antigen dose, almost all solicited systemic adverse reactions were reported on the day 
of vaccination (day 1) or during the 3 days immediately following. 
 
Data on safety of a booster dose are limited to three trials performed with H5N1 MF59C.1 adjuvanted 
vaccine containing A/Vietnam/1194/2004 (V87P1, V87P2) or A/turkey/Turkey/1/2005  (V87P1E1) 
that included 116 adults (18-60 years) and 56 elderly subjects (≥61 years). No increase in solicited 
adverse reactions was reported when a booster dose was administered 6 or 18 months, after the initial 
dosing series. A slight increase in solicited adverse reactions in adults was reported when a booster 
dose was administered 18 months after the initial dosing series. In the elderly, the reported solicited 
adverse reactions increased with the third booster dose only when compared with the second dose. 
 
Tabulated list of adverse reactions 
 
The adverse reaction rates reported after any vaccination dose (i.e. 1st, 2nd or booster) were similar 
and are listed according to the following MedDRA frequency convention and system organ class: 
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). 
 

MedDRA System 
Organ class 

Very common 
(≥1/10) 

Common 
(≥1/100 to <1/10) 

Rare 
(≥1/10,000 to 
˂1/1,000) 

Nervous system 
disorders 

Headache   

Gastrointestinal 
disorders 

 Nausea  

Skin and 
subcutaneous tissue 
disorders 

 Sweating  



24 

Musculoskeletal 
and connective 
tissue disorders 

Myalgia Arthralgia  

General disorders 
and administration 
site conditions 

Injection site 
swelling, Injection 
site pain, Injection 
site induration, 
Injection site redness, 
Fatigue, Chills, 
Malaise 

Injection site 
ecchymosis, Fever  

Anaphylaxis 

 
The majority of these reactions usually disappear within 1-2 days without treatment. 
 
Clinical trials in special populations 
 
Adverse reactions in special populations have been evaluated in two clinical trials, V87_25 and 
V87_26, involving adult (18-60 years) and elderly (≥ 61 years) subjects who were either healthy or 
with underlying medical conditions or immunosuppressive conditions. 
 
 H5N1 MF59C.1 adjuvanted A/turkey/Turkey/1/2005 vaccine 
 Study V87_25 Study V87_26 
 Medical conditions Healthy Immunocompromi

sed Healthy 

 
Adults 
(20-60 
years)* 

Elderly 
(61-84 
years)* 

Adults 
(19-60 
years)* 

Elderly 
(61-79 
years)* 

Adults 
(20-60 
years)* 

Elderly 
(61-84 
years)* 

Adults 
(18-59 
years)* 

Elderly 
(61-91 
years)*  

No. of 
subjects N=145 N=149 N=59 N=58 N=147 N=148 N=58 N=62 

*actual age range of population enrolled 
 
Across studies V87_25 and V87_26, the safety of H5N1 A/turkey/Turkey/1/2005 in healthy adult and 
elderly subjects was consistent with existing safety data from previous clinical trials. However, in 
immunocompromised subjects 18 through 60 years of age, slightly higher rates of nausea (13.0%) 
were reported. In addition, higher rates of arthralgia (up to 23.3%) were reported in both adult and 
elderly subjects, who were immunocompromised or with underlying medical conditions. 
 
The following solicited adverse reactions were additionally collected in these two studies and reported 
with the following frequencies across subjects who received H5N1 A/turkey/Turkey/1/2005 
irrespective of age or health status: diarrhoea (up to 11.9%), loss of appetite (up to 10.9%) and 
vomiting (up to 1.7%). In both studies, subjects with underlying medical and immunosuppressive 
conditions reported higher frequencies of diarrhoea, loss of appetite and vomiting compared to healthy 
subjects (irrespective of age). 
 
Adverse reactions from clinical trial in children aged 6 months to 17 years 
A clinical trial (Study V87P6) was conducted with a H5N1 A/Vietnam/1194/2004 vaccine combined 
with MF59C.1 adjuvant (N=334) vs seasonal influenza vaccine (N=137). 
 
Regardless  of age, reactogencity was higher after the first dose than after the second vaccination. 
Reactogenicity after the third dose, administered 12 months following the second dose, was higher 
than after both first and second doses. The percentages of subjects reporting local adverse reactions 
were higher in the older age groups, mainly due to the higher reports for pain. In toddlers, erythema 
and tenderness were the most frequently reported solicited local adverse reactions; irritability and 
unusual crying were the most frequently reported solicited systemic adverse reactions. In children and 
adolescents, pain was the most frequently reported solicited local adverse reaction, and fatigue and 
headache were the most frequently reported solicited systemic adverse reactions. Across all ages, the 
frequency of fever after any dose was not more than 6%.  



25 

 

 Study V87P6  
H5N1 MF59C.1 adjuvanted A/Vietnam/1194/2004 vaccine 

 First dose 
Second dose 

(21 days after first 
dose) 

Third dose 
(12 months after 

second dose) 
Toddlers (6 to 

35 months) 
N=145 N=138 N=124 

Any 76% 68% 80% 
Local 47% 46% 60% 
Systemic 59% 51% 54% 
Fever ≥ 38°C (≥ 40°C) 0% 0% 0%  
Any Other Adverse Event 54% 49% 35% 

Children (3 to 8 years) N=96 N=93 N=85 
Any 72% 68% 79% 
Local 66% 58% 74% 
Systemic 32% 33% 45% 
Fever ≥ 38°C (≥ 40°C) 4%  2%  6%  
Any Other Adverse Event 36% 31% 19% 

Adolescents(9 to 
17 years) 

N=93 N=91 N=83 

Any 91% 82% 89% 
Local 81% 70% 81% 
Systemic 69% 52% 69% 
Fever ≥ 38°C (≥ 40°C) 0%  1%  2%  
Any Other Adverse Event 30% 27% 22% 

 
Focetria (an MF59.1 adjuvanted H1N1 pandemic vaccine similar to Foclivia). 
 
Adverse reactions in the week following vaccination with Focetria H1N1v from 77 children 3-8 years 
old and 80 children and adolescents 9-17 years old receiving the 7.5 µg formulation were reported as 
follows: 
 

 Injection 1 Injection 2 
Children (3 to 8 years of age) N= 77 N= 75 

Any adverse reaction  74%  69% 
Local  62%  56% 
Systemic  39%  35% 
Fever ≥ 38°C to 38.9°C  4% 1% 
Fever 39°C to 39.9°C 0% 1% 
Fever ≥ 40° C 0% 0% 
Any other AE  14%  17% 
Adolescents (9 to 17 years of age) N= 80 N= 79 

Any adverse reaction  79%  66% 
Local  70%  58% 
Systemic  45%  30% 
Fever ≥ 38°C to 38.9°C  3% 1% 
Fever 39°C to 39.9°C 0% 0% 
Fever ≥ 40° C 0% 0% 
Any other AE  13%  10% 

 
Data in children and adolescents 3-17 years suggest a slight decrease in reactogenicity after the second 
dose, with no increase in rates of fever. 
 
Very common reactions reported in children and adolescents 3 to 17 years of age: 



26 

Pain, induration and erythema, malaise, myalgia, headache and fatigue. 
 
Adverse reactions in the week following vaccination with Focetria H1N1v from 
73 infants 6-11 months old and 73 toddlers 12-35 months old, receiving the 7.5 µg formulation were 
reported as follows: 
 

 Injection 1 Injection 2 
Infants (6 to 11 months of age) N= 73 N= 68 

Any adverse reaction 79% 65% 
Local 44%  26% 
Systemic  70%  56% 
Fever ≥ 38°C to 38.9°C  11%  9% 
Fever 39°C to 39.9°C  3% 4% 
Fever ≥ 40° C 0% 0% 
Any other AE  32%  31% 
Toddlers (12 to 35 months of age) N= 73 N= 71 

Any adverse reaction 70%  71% 
Local  51%  49% 
Systemic  60%  49% 
Fever ≥ 38°C to 38.9°C  10% 11% 
Fever 39°C to 39.9°C 4% 1% 
Fever ≥ 40° C 1% 0% 
Any other AE 21%  24% 

 
Data in infants and toddlers 6-35 months of age suggest a slight decrease in reactogenicity after the 
second dose, with no increase in rates of fever. 
 
Very common reactions reported in 146 infants and toddlers 6 to 35 months of age: 
Tenderness, erythema, irritability, unusual crying, sleepiness, diarrhoea, vomiting and change in eating 
habits. Induration and ecchymosis were very common reactions in toddlers but were less common in 
infants. 
 
• Post-marketing surveillance 
 
No post-marketing surveillance data are available following Foclivia administration. 
 
The following adverse events were reported from post-marketing surveillance with Focetria (an H1N1 
pandemic vaccine similar to Foclivia) which contains the same amount of adjuvant MF59C.1 as 
Foclivia, approved for use in children 6 months of age and above, adults and the elderly: 
 
Blood and lymphatic system disorders 
Lymphadenopathy. 
 
Immune system disorders 
Allergic reactions, anaphylaxis including dyspnoea, bronchospasm, laryngeal oedema, in rare cases 
leading to shock, angioedema. 
 
Nervous system disorders 
Headache, dizziness, somnolence, syncope. Neurological disorders, such as neuralgia, paraesthesia, 
convulsions and neuritis. 
 
Cardiac disorders 
Palpitation, tachycardia. 
 
Respiratory disorders 
Cough. 



27 

 
Gastrointestinal disorders 
Gastrointestinal disorders such as nausea, vomiting, abdominal pain and diarrhoea.  
 
Skin and subcutaneous tissue disorders 
Generalised skin reactions including pruritus, urticaria or non-specific rash. 
 
Musculoskeletal, connective tissue and bone disorders 
Muscular weakness, pain in extremities. 
 
General disorders and administration site conditions 
Asthenia. 
 
The following additional adverse events were reported from post-marketing surveillance with seasonal 
non-adjuvanted trivalent vaccines in all age groups and a seasonal trivalent MF59-adjuvanted subunit 
influenza vaccine approved for use in elderly subjects 65 years of age and older: 
 
Blood and lymphatic system disorders 
Thrombocytopenia (in some cases reversible platelet counts less than 5000 mm3). 
 
Nervous system disorders 
Neurological disorders, such as encephalomyelitis and Guillain Barré syndrome. 
 
Vascular disorders 
Vasculitis which may be associated with transient renal involvement. 
 
Skin and subcutaneous tissue disorders 
Erythema multiforme. 
 
General disorders and administration site conditions 
Extensive swelling of injected limb lasting more than one week, injection-site cellulitis-like reaction 
(some cases of swelling, pain, and redness extending more than 10 cm and lasting more than 1 week). 
 
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 Appendix V 
 
4.9 Overdose 
 
No case of overdose has been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02 
 
Clinical efficacy and safety 
 
Pandemic preparedness 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 a pandemic preparedness vaccine will support a vaccination strategy that is likely to be 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


28 

used for the pandemic vaccine: clinical efficacy and safety data obtained with pandemic preparedness 
vaccines are relevant for the pandemic vaccines. 
 
Immune response to H5N1 vaccine combined with MF59C.1 adjuvant containing 
A/Vietnam/1194/2004 or A/turkey/Turkey/1/2005 strain. 
 
Adults (18-60 years) 
 
A Phase II clinical trial (V87P1) was conducted with  H5N1  MF59C.1 
adjuvanted  vaccine  containing A/Vietnam/1194/2004 in 312 healthy adults. Two doses of vaccine co
ntaining  7.5 µg Haemagglutinin(HA)/dose were administered three weeks apart to 156 subjects. 
Immunogenicity was assessed in 149 subjects. 
 
In a phase III clinical trial (V87P13), 2693  adult subjects were enrolled and 2566 received two doses 
of H5N1 MF59C.1 adjuvanted vaccine containing A/Vietnam/1194/2004 7.5 µg   HA/dose 
administered three weeks apart. Immunogenicity was assessed in a subset (N=197) of subjects. 
 
In a third clinical trial (V87P11) 194 adult subjects received two doses of H5N1 MF59C.1 adjuvanted 
vaccine containing A/turkey/Turkey/1/2005 7.5 µg HA/dose administered three weeks apart. 
Immunogenicity was assessed in 182 subjects. 
 
The seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA 
antibody to H5N1 A/Vietnam/1194/2004 and to H5N1 A/turkey/Turkey/1/2005 in the adults measured 
by Single Radial Haemolysis (SRH) assay was as follows: 
 

Anti-HA 
antibody 
(SRH) 

Study V87P1 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=149 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=197 

Study V87P11 
A/turkey/Turkey/1/2005 

21 days after 2nd dose 
N=182 

Seroprotection 
rate (95%CI)* 

85% (79-91) 91% (87-95) 91% (85-94) 

Seroconversion 
rate 
(95%CI)** 

85% (78-90) 78% (72-84) 85% (79-90) 

Seroconversion 
factor 
(95%CI)*** 

7.74 (6.6-9.07) 4.03 (3.54-4.59) 6 (5.2-6.93) 

 

Anti-HA antibody (SRH) 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=69 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=128 

 
- 

Baseline Serostatus < 4 mm2 ≥ 4 mm2 - 
Seroprotection rate 
(95%CI)* 

87% (77-94) 94% (88-97) - 

Seroconversion rate 
(95%CI)** 

87% (77-94) 73% (65-81) - 

Seroconversion factor 
(95%CI)*** 

8.87 (7.09-11) 2.71 (2.38-3.08) - 

* Seroprotection: SRH area ≥25 mm2 
** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 

area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

***  geometric mean ratios (GMRs) of SRH 
 



29 

MicroNeutralization (MN) results against A/Vietnam/1194/2004 (Studies V87P1 and V87P13) 
indicate a seroprotection and seroconversion rate ranging from 67% (60-74) to 85% (78-90) and 65% 
(58-72) to 83% (77-89), respectively. Immune response to vaccination assessed by MN assay is in line 
with results obtained with SRH. 
 
In Study V87P11 MN results against homologous A/turkey/Turkey/1/2005 indicate a seroprotection 
and seroconversion rate of 85% (79-90) and 93% (89-96), respectively. Immune response to 
vaccination assessed by MN assay is in line with results obtained with SRH. 
 
Persistence of antibodies after primary vaccination in this population was assessed by 
Hemagglutination Inhibition (HI), SRH, and MN assays. Compared to the antibody levels obtained at 
day 43 after completion of primary vaccination schedules, antibody levels at day 202 were reduced 
by 1/5 to 1/2 from their prior levels. 
 
Elderly (≥61 years) 
 
The seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA 
antibody to H5N1 MF59C.1 adjuvanted vaccine (A/Vietnam/1194/2004 and A/turkey/Turkey/1/2005) 
in subjects aged 61 years and older (limited number of subjects were above 70 years of age; N=123) 
measured by SRH assay assessed in two clinical studies were as follows: 
 

Anti-HA antibody 
(SRH) 

Study V87P1 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=84a 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=210b 

Study V87P11 
A/turkey/Turkey/1/2005 

21 days after 2nd dose 
N=132c 

Seroprotection rate 
(95%CI)* 

80% (70-88) 82% (76-87) 82% (74-88) 

Seroconversion rate 
(95%CI)** 

70% (59-80) 63% (56-69) 70% (61-77) 

Seroconversion factor 
(95%CI)*** 

4.96 (3.87-6.37) 2.9 (2.53-3.31) 3.97 (3.36-4.69) 

 

Anti-HA antibody (SRH) 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=66 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=143 
Baseline Serostatus < 4 mm2 ≥ 4 mm2 
Seroprotection rate (95%CI)* 82% (70-90) 82% (75-88) 
Seroconversion rate (95%CI)** 82% (70-90) 54% (45-62) 
Seroconversion factor (95%CI)*** 8.58 (6.57-11) 1.91 (1.72-2.12) 

a  Ages 62-88 years; b Ages 61-68 years; c Ages 61-89 years 
* Seroprotection: SRH area ≥25 mm2 
** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 

area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
 
MN results against A/Vietnam/1194/2004 (Studies V87P1 and V87P13) indicate a seroprotection and 
seroconversion rate ranging from 57% (50-64) to 79% (68-87) and 55% (48-62) to 58% (47-69) 
respectively. MN results, similar to SRH results, demonstrated strong immune response after 
completion of priming vaccination series in a population of elderly subjects. 
 
In Study V87P11, MN results against homologous A/turkey/Turkey/1/2005 indicate a seroprotection 
and seroconversion rate of 68% (59-75) and 81% (74-87), respectively. Immune response to 
vaccination assessed by MN assay is similar to SRH results. 
 
Persistence of antibodies after primary vaccination in this population as assessed by HI, SRH, and MN 
tests reduced from 1/2 to 1/5 of their post-vaccination level at day 202 as compared to day 43 after 



30 

completion of primary schedules as assessed by HI, SRH, and MN tests. Up to 50% (N=33) of the 
elderly subjects aged 62 to 88 years immunised with H5N1  MF59C.1 adjuvanted vaccine containing 
A/Vietnam/1194/2004 in trial V87P1 were seroprotected at six months. 
 
A third (booster) dose of H5N1 vaccine combined with MF59C.1 was administered 6 months after the 
primary vaccination series. Results are shown by SRH. 
 
The seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA 
antibody to H5N1 A/Vietnam/1194/2004 measured by SRH assays were as follows: 
 

 
Study V87P1 Adults 

A/Vietnam/1194/2004 
booster after 2nd dose 

Study V87P2 Adults 
A/Vietnam/1194/2004 
booster after 2nd dose 

Study V87P1 Elderly 
A/Vietnam/1194/2004 
booster  after 2nd dose 

SRH N=71 N=13 N=38 
Seroprotection rate 
(95%CI)* 

89% (79-95) 85% (55-98) 84% (69-94) 

Seroconversion rate 
(95%CI)** 

83% (72-91) 69% (39-91) 63% (46-78) 

Seroconversion fact
or (95%CI)*** 

5.96 (4.72-7.53) 2.49 (1.56-3.98) 5.15 (3.46-7.66) 

* Seroprotection: SRH area ≥25 mm2 
** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 

area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
 
• Supportive data in adult and elderly populations 
 
In two dose finding studies 80 adults received an adjuvanted pandemic preparedness vaccine (H5N3 or 
H9N2). Two doses of vaccine with H5N3 (A/Duck/Singapore/97) strain at 3 different dosages 
(7.5, 15 and 30 µg HA/dose) were administered three weeks apart. 
 
Serum samples were tested against the original H5N3 and also a number of H5N1 isolates. 
 
Serologic responses obtained with the SRH assay showed that 100% of subjects achieved 
seroprotection and 100% seroconverted after two 7.5 µg injections. The adjuvanted vaccine was also 
found to induce antibodies that cross-protected against the H5N1 strains isolated in 2003 and 2004, 
which exhibit some antigenic drift compared to the original strains. 
 
Two doses of vaccine containing H9N2 (A/chicken/Hong Kong/G9/97) strain at 4 different dosages 
(3.75, 7.5, 15 and 30 µg HA/dose), were administered four weeks apart. Serologic responses obtained 
with the HI assay showed that 92% of subjects achieved seroprotection and 75% seroconverted after 
two 7.5 µg injections. 
 
Cross reactivity 
 

Cross-reactive immune response elicited by H5N1 A/Vietnam/1194/2004 against 
A/turkey/Turkey/1/2005 and A/Indonesia/5/2005 

 
Adults (18-60 years) 
 
Some heterologous immune response against A/turkey/Turkey/1/2005 (NIBRG23; clade 2.2.1) and 
A/Indonesia/5/2005 (clade 2.1) was detectable both after the second and third vaccinations, indicating 
cross-reactivity of the clade 1 vaccine against clade 2 strains. 
 



31 

Seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA antibodies 
to H5N1 A/turkey/Turkey/1/2005 after the 2nd dose in adults 18-60 years of age, measured by SRH 
and HI assays were as follows: 
 

 Anti-HA 
antibody 

Study V87P1 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose  
N=70 

Study V87P12 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose 
N=60 

Study V87P3 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose 
N=30 

Study V87P13 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose 
N=197 

SR
H 

Seroprotectio
n rate 
(95%CI)* 

70% (58-80) 65% (52-77) 90% (73-98) 59% (52-66) 

Seroconversio
n rate 
(95%CI)** 

NAǂ 65% (52-77) 86% (68-96) 49% (42-56) 

Seroconversio
n 
factor(95%CI)
*** 

NAǂ 4.51 (3.63-5.61) 7.67 (6.09-9.67) 2.37 (2.1-2.67) 

  N=69 N=60 N=30 N=197 
HI Seroprotectio

n rate 
(95%CI)° 

36% (25-49) 28% (17-41) 24% (10-44) 23% (18-30) 

Seroconversio
n rate 
(95%CI)° 

NAǂ 28% (17-41) 21% (8-40) 19% (14-25) 

Seroconversio
n factor 
(95%CI)°° 

NAǂ 2.3 (1.67-3.16) 1.98 (1.22-3.21) 1.92 (1.64-2.25) 

* Seroprotection: SRH area ≥25 mm2 

** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 
area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
ǂ In V87P1: baseline not tested 
° measured by HI assay ≥40 
°° GMRs of HI 
 
MN results for the clinical studies V87P12, V87P3 and V87P13 in the Table above revealed a 
seroprotection rate and seroconversion rate against A/turkey/Turkey/2005 ranging from 10% (2-27) 
to 39% (32-46) and 10% (2-27) to 36% (29-43) respectively. MN results yielded a GMR against 
A/turkey/Turkey/2005 ranging from 1.59 to 2.95. 
 
Elderly (≥61 years) 
 
Seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibodies 
to H5N1 A/turkey/Turkey/05 after the 2nd dose in elderly subjects ≥61 years of age, measured by SRH 
and HI assays were as follows: 
 

 Anti-HA antibody 

Study V87P1 
A/Vietnam/1194/2004 
 
21 days after 2nd dose 
N=37 

Study V87P13 
A/Vietnam/1194/2004 
 
21 days after 2nd dose 
N=207 

SRH Seroprotection rate (95%CI)* 57% (39-73) 20% (18-23) 
Seroconversion rate (95%CI)* NA*** 48% (41-55) 



32 

Seroconversion factor (95%CI)** NA*** 1.74 (1.57-1.94) 
  N=36 N=208 

HI 
Seroprotection rate (95%CI)° 36% (21-54) 25% (19-32) 
Seroconversion rate (95%CI)° NA*** 19% (14-25) 
Seroconversion factor (95%CI)°° NA*** 1.79 (1.56-2.06) 

* measured by SRH assay ≥25 mm2 
** geometric mean ratios of SRH 
° measured by HI assay ≥40 
°° geometric mean ratios of HI 
*** In V87P1: baseline not tested 
 
MN results for the clinical studies in the Table above revealed a seroprotection rate against 
A/turkey/Turkey/05 ranging from 11% (3-25) (study V87P1) to 30% (24-37) (study V87P13) and 
seroconversion rate of 25% (19-31) for study V87P13. MN results in study V87P13 yielded a GMR 
against A/turkey/Turkey/05 of 2.01 (1.78-2.26). 
 

Cross-reactive immune response elicited by A/turkey/Turkey/1/2005 against 
A/Indonesia/5/2005 and A/Vietnam/1194/2004 

 
Heterologous immune response against A/Indonesia/5/2005 (clade 2.1) was detectable in Study 
V87P11 after the second vaccination, indicating cross-reactivity of the clade 2.2.1 vaccine against 
clade 2.1 strains. 
 
Seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA antibodies 
to H5N1 A/Indonesia/5/2005 and A/Vietnam/1194/2004 after the 2nd dose in adults (18-60 years) and 
elderly (> 61years), measured by SRH and HI assays were as follows: 
 

Anti-HA 
antibody 

 V87P11 Adults (18-60 years) 
N=186 

V87P11 Elderly (>61-89 years)a 
N=142 

  A/Indonesia/ 
5/2005 

A/Vietnam/ 
1194/2004 

A/Indonesia/ 
5/2005 

A/Vietnam/ 
1194/2004 

SRH Seroprotection 
rate (95%CI)* 

83 
(77-88) 

62 
(54-69) 

61 
(52-69) 

45 
(37-54) 

 Seroconversion 
rate (95%CI)** 

79 
(72-85) 

60 
(53-68) 

64 
(56-73) 

44 
(35-53) 

 Seroconversion 
factor 
(95%CI)*** 

6.24 
(5.44-7.16) 

4.45 
(3.85-5.14) 

3.87 
(3.31-4.53) 

3.03 
(2.56-3.58) 

  N=194 N=148 
HI Seroprotection 

rate (95%CI) ° 
50 

(43-57) 
47 

(40-55) 
34 

(26-42) 
39 

(31-48) 
 Seroconversion 

rate (95%CI) ° 
49 

(42-56) 
44 

(37-51) 
32 

(25-41) 
34 

(26-42) 
 Seroconversion 

factor (95%CI) °° 
4.71 

(3.74-5.93) 
4.25 

(3.36-5.37) 
2.69 

(2.18-3.32) 
2.8 

(2.2-3.55) 
a  actual age range of population enrolled 
* Seroprotection: SRH area ≥25mm2 

** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 
area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
° measured by HI assay ≥40 
°° GMRs of HI 
 
MN results for A/Indonesia/5/2005 revealed a seroprotection rate of 38% (31-45) in adults 
(18-60 years) and 14% (8-20) in elderly (>61 years); a seroconversion rate of 58% (50-65) in adults 
and 30% (23-38) in elderly and finally a GMR of 4.67 (3.95-5.56) in adults and 2.19 (1.86-2.58) 
in elderly. 
 



33 

MN results for A/Vietnam/1194/2004 revealed a seroprotection rate of 10% (6-16) in adults 
(18-60 years) and 6% (3-11) in elderly (>61 years); a seroconversion rate of 19% (13-25) in adults 
and 7% (4-13) in elderly and finally a GMR of 1.86 (1.63-2.12) in adults and 1.33 (1.17-1.51) 
in elderly. 
 
Long term booster immune memory: 
 
A single vaccination with H5N1 MF59C.1 adjuvanted A/Vietnam/1194/2004 vaccine induced high 
and rapid serological response in subjects primed 6-8 years previously with two doses of a different 
vaccine, having the same formulation but using the H5N3 strain. 
 
In a phase I clinical trial (V87P3) adult subjects aged 18-65 years primed 6-8 years previously with 2 
doses of MF59-adjuvanted H5N3 vaccine/A/Duck/Singapore/97, were administered 2 booster doses of 
H5N1 MF59C.1 adjuvanted A/Vietnam/1194/2004 vaccine. SRH results after the first dose, that 
mimic prepandemic priming plus single heterologous booster dose, revealed seroprotection and 
seroconversion rates of 100% (74- 100) and an 18-fold increase in SRH area (GMR). 
 
Alternative vaccination schedules: 
 
In a clinical trial evaluating 4 different vaccination schedules in 240 subjects 18 to 60 years of age, 
where the second dose occurred either 1, 2, 3 or 6 weeks after the first dose of H5N1 MF59C.1 
adjuvanted A/Vietnam/1194/2004 vaccine, all vaccine schedule groups after 3 weeks from the 2nd 
vaccination achieved high levels of antibodies as evaluated with SRH. SRH seroprotection rates 
ranged from 86% to 98%, seroconversion rates from 64% to 90%, and GMR ranged from 2.92 to 4.57. 
The magnitude of immune response was lower in the group who received the 2nd dose 1 week later and 
higher in the groups with longer interval schedules. 
 
Subjects with underlying medical or immunosuppressive conditions: 
 
Immunogenicity of H5N1 A/turkey/Turkey/1/2005 in adults (18 to 60 years) and elderly (>61 years) 
subjects with underlying medical conditions (Study V87_25) or immunosuppressive conditions 
(mainly HIV-infected subjects) (Study V87_26) in comparison to healthy adults (18-60 years) and 
elderly (>61 years), was evaluated in two randomised, phase III controlled clinical trials (with a 
seasonal trivalent inactivated MF59-adjuvanted subunit influenza vaccine approved for use in elderly 
subjects 65 years of age and older as a comparator). In trial V87_25 and V87_26, 96 and 67 subjects, 
respectively, were over the age of 70 years. In both trials, immunogenicity of 
H5N1 A/turkey/Turkey/1/2005 was shown by HI, SRH and MN assays following both the first and 
second dose.  
 
Geometric mean area*, seroprotection rate*, seroconversion rate* and the seroconversion factor** for 
anti-HA antibody to H5N1 A/turkey/Turkey/1/2005 measured by SRH assays 21 days after the 2nd 
dose were as follows: 
 

Study V87_25 

 
Adults 

 (20- 60 years)a  
Adults  

(19- 60 years)a 
Elderly  

(61-84 years)a 
 

Elderly 
(61-79 years)a 

 

Anti-HA antibody 
(SRH) 

Medical 
Conditions 

N=140 

Healthy 
N=57 

Medical 
Conditions 

N=143 

Healthy 
N=57 

Geometric Mean 
Area (95%CI)* 

31.07 
(27.43-35.19) 

58.02 
(48.74-69.06) 

29.34 
(26.07-33.01) 

27.78 
(22.57-34.18) 

Seroprotection rate 
(95%CI)* 

65.00 
(56.5-72.9) 

89.47 
(78.5-96) 

58.74 
(50.2-66.9) 

57.89 
(44.1-70.9) 

Seroconversion rate 
(95%CI)* 

72.86 
(64.7-80) 

98.25 
(90.6-99.96) 

64.34 
(55.9-72.2) 

66.67 
(52.9-78.6) 



34 

a  actual age range of population enrolled 
*  measured by SRH assay seroprotection: SRH area ≥25 mm2, seroconversion: SRH area ≥25 mm2 for subjects with a 

baseline SRH area ≤4 mm2 or a minimum 50% increase in SRH area for subjects with >4 mm2. 
** geometric mean ratios of SRH 

 
HI results for the two clinical studies revealed lower values than those reported in previous studies. 
Seroconversion rates against homologous A/turkey/Turkey/1/2005 ranged from 37.50% to 43.10% in 
healthy adults, and from 19.18% to 26.47% in adults with immunosuppressive or underlying medical 
conditions, respectively; seroconversion rates ranged from 21.43% to 30.65% in healthy elderly 
subjects, and from 24.49% to 27.86% in elderly subjects with immunosuppressive or underlying 
medical conditions. Similar trends were observed for seroprotection rates in both studies. 
 
MN results against homologous A/turkey/Turkey/1/2005 indicate a seroconversion rate of 66.67% in 
healthy adults, and ranging from 33.57% to 54.14% in adults with immunosuppressive or underlying 
medical conditions, respectively; seroconversion rates ranged from 24.39% to 29.03% in healthy 
elderly subjects, and from 31.65% to 39.42% in elderly subjects with immunosuppressive or 
underlying medical conditions. Similar trends were observed for seroprotection rates in both studies. 
 
In both studies V87_25 and V87_26, the lower levels of antibodies (as measured by HI, SRH and MN 
assays) and reduced seroprotection rates in adults and elderly (≥ 61 years old) subjects with underlying 
medical or immunosuppressive conditions, suggest that H5N1 A/turkey/Turkey/1/2005 may not elicit 
the same level of protection against A/H5N1 strain as compared to healthy adults (see section 4.4). 
These studies provided limited immunogenicity data in subjects with some underlying medical (in 
particular, renal impairment and peripheral cardiovascular disease) and immunosuppressive conditions 
(in particular, transplant recipients and patients under cancer treatment). In these trials, lower levels of 
antibodies and reduced seroprotection rates against homologous H5N1 A/turkey/Turkey/1/2005 were 
also measured in healthy elderly subjects, as compared to healthy adults, though previous studies 
showed induction of sufficiently immunogenic responses against H5N1 strains (see above for 
information on elderly). 
 

Seroconversion 
factor (95%CI)** 

3.33 
(2.94-3.77) 

6.58 
(5.53-7.83) 

2.37 
(2.10-2.66) 

2.96 
(2.41-3.64) 

Study V87_26 

 
Adults  

(20- 60 years)a   
Adults 

(18-59 years)a 
Elderly  

(61-84 years)a 
 

Elderly  
(61-91 years)a 

 

Anti-HA antibody 
(SRH) 

Immuno- 
compromised 

N=143 

Healthy 
N=57 

Immuno- 
compromised 

N=139 

Healthy 
N=62 

Geometric Mean 
Area (95%CI)* 

26.50 
(22.49-31.22) 

48.58 
(40.01-58.99) 

26.85 
(23.01-31.33) 

23.91 
(18.89-30.26) 

Seroprotection rate 
(95%CI)* 

60.84 
(52.3-68.9) 

87.72 
(76.3-94.9) 

58.99 
(50.3-67.3) 

53.23 
(40.1-66) 

Seroconversion rate 
(95%CI)* 

61.54 
(53-69.5) 

89.47 
(78.5-96) 

64.75 
(56.2-72.7) 

56.45 
(43.3-69) 

Seroconversion 
factor (95%CI)** 

3.16 
(2.69-3.73) 

7.10 
(5.85-8.62) 

3.15 
(2.70-3.68) 

2.83 
(2.24-3.58) 



35 

Available data in paediatric populations 
 
A clinical trial (V87P6) was conducted with a H5N1 A/Vietnam/1194/2004 vaccine combined with 
MF59C.1 adjuvant in 471 children from 6 months to 17 years of age. Two doses of 7.5 µg were 
administered three weeks apart and a third dose 12 months following the first dose. After 3 weeks 
from the 2nd vaccination (day 43) all age groups (i.e. 6-35 months, 3-8 years and 9-17 years) achieved 
high levels of antibodies to A/Vietnam/1194/2004 as evaluated with SRH and HI assays as presented 
in table below. In this trial no vaccine related SAEs were observed. 
 

 Toddlers (6 to 
35 months) 

Children  
(3 to 8 years) 

Adolescents (9 to 
17 years) 

N=134 N=91 N=89 

HI 

Seroprotection rate 
(95% CI) 
Day 43 

97% 
(92-99) 

97% 
(91-99) 

89% 
(80-94) 

Seroconversion 
factor (95% CI) 
Day 43 to Day 1 

129 
(109-151) 

117 
(97-142) 

67 
(51-88) 

Seroconversion 
rate (95% CI) 

Day 43 

97% 
(92-99) 

97% 
(91-99) 

89% 
(80-94) 

SRH 

 N=133 N=91 N=90 
Seroprotection rate 

(95% CI) 
Day 43 

100% 
(97-100) 

100% 
(96-100) 

100% 
(96-100) 

Seroconversion 
factor (95% CI) 
Day 43 to Day 1 

16 
 (14-18) 

15 
 (13-17) 

14 
 (12-16) 

Seroconversion 
rate (95% CI) 

Day 43 

98% 
(95-100) 

100% 
(96-100) 

99% 
(94-100) 

 
MN results against a A/Vietnam/1194/2004 indicate a seroprotection rate of 99% (95%CI: 94-100), 
a seroconversion rate ranging from 97% (95%CI: 91-99) to 99% (95%CI: 96-100) and a GMR ranging 
from 29 (95%CI: 25-35) to 50 (95%CI: 44-58). 
 
Immunogenicity results with Focetria H1N1v (Study V111_03): 
The seroprotection rate and seroconversion rate measured by HI assay and the seroconversion factor 
expressed as geometric mean ratio of HI for anti-HA antibody to H1N1 after administration of one and 
two 7.5 µg doses of Focetria was evaluated in 70 children and adolescents (9-17 years), 60 children 
(3-8 years), 58 children (12-35 months) and 49 infants (6-11 months). CHMP immunogenicity criteria 
set for adults (18-60 years) were met both after the 1st and the 2nd dose in all the above age strata (both 
in the overall population and in the subset seronegative at baseline). 
 
The European medicines Agency has deferred the obligation to submit the results of studies with 
Foclivia in one or more subsets of the paediatric populations in active immunisation against 
H5N1 subtype of Influenza A virus. See section 4.2 for information on paediatric use. 
 
Foclivia 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. 
 
5.2 Pharmacokinetic properties 
 
Not applicable. 
 



36 

5.3 Preclinical safety data 
 
Non-clinical data obtained with Foclivia and with seasonal influenza vaccine containing 
MF59C.1 adjuvant reveal no special hazard for humans based on conventional studies of repeated 
dose toxicity, local tolerance, female fertility, and reproductive and developmental toxicity (through 
the end of the lactation period). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride, 
Potassium chloride, 
Potassium dihydrogen phosphate, 
Disodium phosphate dihydrate, 
Magnesium chloride hexahydrate, 
Calcium chloride dihydrate, 
Water for injections. 
 
For the adjuvant, see section 2. 
 
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. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. Discard if the vaccine has been frozen. Store in the 
original package in order to protect from light. 
 
6.5 Nature and contents of container 
 
0.5 ml in single-dose vial (type I glass) with stopper (halo-butyl rubber). Packs of 10. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Gently shake before use. 
After shaking, the normal appearance of Foclivia is a milky-white suspension. 
 
Visually inspect the suspension prior to administration. In case of any particles and/or abnormal 
appearance, the vaccine should be discarded. 
 
Any unused vaccine or waste material should be disposed of in accordance with local requirements. 
 
 



37 

7. MARKETING AUTHORISATION HOLDER 
 
Seqirus S.r.l. 
Via del Pozzo 3/A, S. Martino 
53035 Monteriggioni (SI) 
Italy 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/577/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 October 2009 
Date of latest renewal: 19 October 2014 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/. 

http://www.ema.europa.eu/


38 

1. NAME OF THE MEDICINAL PRODUCT 
 
Foclivia suspension for injection in multidose container 
Pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain: 
 
A/Vietnam/1194/2004 (H5N1) 7.5 micrograms** 
per 0.5 ml dose 
 
* propagated in fertilised hens’ eggs from healthy chicken flocks 
** expressed in microgram haemagglutinin. 
 
Adjuvant MF59C.1 containing: 
Squalene 9.75 milligrams 
Polysorbate 80 1.175 milligrams 
Sorbitan trioleate 1.175 milligrams 
Sodium citrate 0.66 milligrams 
Citric acid 0.04 milligrams 
 
Excipients: 
Thiomersal 0.05 milligrams 
 
This is a multidose container. See section 6.5 for the number of doses per vial. 
 
This vaccine complies with the WHO recommendations and EU decision for the pandemic. 
 
Excipient with known effect: 
The vaccine contains 1.899 milligrams of sodium and 0.081 milligrams of potassium per 0.5 ml dose.  
 
Foclivia may contain trace residues of egg and chicken proteins, ovalbumin, kanamycin sulphate, 
neomycin sulphate, formaldehyde and cetyltrimethylammonium bromide which are used during the 
manufacturing process (see section 4.3). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection. 
Milky-white liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Prophylaxis of influenza in an officially declared pandemic situation. 
Foclivia should be used in accordance with Official Guidance. 
 



39 

4.2 Posology and method of administration 
 
Posology 
 
Adults and elderly (18 years of age and above): 0.5 ml at an elected date. 
A second dose of vaccine should be given after an interval of at least 3 weeks. 
 
Foclivia was evaluated in adults (aged 18 to 60 years old) and elderly (over 60 years old) following 
a 1, 22 day primary vaccination schedule. 
 
Data on a third dose (booster) administered 6 months after the first dose are limited 
(see sections 4.8 and 5.1). 
 
Paediatric population 
The safety and efficacy of Foclivia in subjects under 18 years of age have not yet been established. 
Currently available data in subjects aged 6 months to 18 years of age are described in section 5.1 but 
no recommendation on a posology can be made. 
 
No data are available in children aged less than 6 months. 
 
Method of administration 
Immunisation should be carried out by intramuscular injection into the deltoid muscle or anterolateral 
thigh (depending on the muscle mass). 
 
4.3 Contraindications 
 
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues 
(eggs, chicken proteins, ovalbumin, kanamycin sulphate,  neomycin sulphate, formaldehyde and 
cetyltrimethylammonium bromide) of this vaccine. However, in a pandemic situation, it may be 
appropriate to give this vaccine to individuals with a history of anaphylaxis as defined above, provided 
that facilities for resuscitation are immediately available in case of need. See section 4.4. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Caution is needed when administrating this vaccine to persons with a known hypersensitivity  to the 
active substance, to any of the excipients listed in section 6.1, to thiomersal and to residues (eggs, 
chicken proteins, ovalbumin, kanamycin sulphate,  neomycin sulphate, formaldehyde and 
cetyltrimethylammonium bromide). 
 
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 should be postponed in patients with febrile illness 
until the fever is resolved. 
 
The vaccine should under no circumstances be administered intravascularly or intradermally. There 
are no data with Foclivia using the subcutaneous route of administration. 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 bleeding. 
 
Protection against influenza 
There is no immune correlate of protection established for influenza A (H5N1).  



40 

A protective immune response may not be elicited in all vaccine recipients. In addition, antibody 
responses in patients with endogenous or iatrogenic immunosuppression may be insufficient to 
provide protection. 
 
Some degree of cross-reactive immunity has been observed against H5N1 viruses of clades different to 
that of the vaccine strain. However, the degree of protection that may be elicited to H5N1 strains of 
other clades is unknown (see section 5.1). 
 
Since a second dose is recommended, it should be noted that there are no safety, immunogenicity 
or efficacy data to support interchangeability of Foclivia with other H5N1 monovalent vaccines. 
 
While no data are available from the use of Foclivia, cases of convulsion with and without fever have 
been reported in subjects vaccinated with Focetria, an MF59.1 adjuvanted H1N1 pandemic vaccine 
similar to Foclivia. 
 
The majority of febrile convulsions occurred in paediatric subjects. Some cases were observed in 
subjects with a history of epilepsy. Particular attention should be given to subjects suffering from 
epilepsy and the physician should inform the subjects (or parents) about the possibility to experience 
convulsion. (see section 4.8). 
 
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to 
the needle injection. This can be accompanied by several neurological signs such as transient visual 
disturbance, paraesthesia and tonic-clonic limb movements during recovery. It is important that 
procedures are in place to avoid injury from faints. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Foclivia may be co-administered with non-adjuvanted seasonal influenza vaccines, and immunisation 
should be carried out on separate limbs. 
 
There are no data on co-administration of Foclivia with vaccines other than non-adjuvanted seasonal 
influenza vaccines. If co-administration with another vaccine is considered, immunisation should be 
carried out on separate limbs. It should be noted that the adverse reactions may be intensified. 
 
The immunological response may be diminished if the patient is undergoing immunosuppressant treatment. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Limited data obtained from women who became pregnant during the course of clinical trials with 
Foclivia or other pandemic vaccines adjuvanted with MF59C.1 were insufficient to inform vaccine-
associated risks in pregnancy. 
 
However, it is estimated that during the 2009 H1N1 pandemic more than 90,000 women were 
vaccinated during pregnancy with Focetria (an H1N1 pandemic vaccine similar to Foclivia) which 
contains the same amount of MF59C.1 as Foclivia. Post-marketing spontaneously reported adverse 
events and an interventional study do not suggest direct or indirect harmful effects of Focetria 
exposure on pregnancy. In addition, two large observational studies designed to assess the safety of 
Focetria exposure in pregnancy showed no increase in the rates of gestational diabetes, preeclampsia, 
abortions, stillbirth, low birth weight, prematurity, neonatal deaths, and congenital malformations 
among almost 10,000 vaccinated pregnant women and their offspring compared with unvaccinated 
controls. 
 
Health care providers need to assess the benefits and potential risks of administering Foclivia vaccine 
to pregnant women, taking into consideration official recommendations. 
 
Breast-feeding 



41 

There are no data regarding the use of Foclivia during breast-feeding. The potential benefits and risks 
to the mother and infant should be considered before administering Foclivia. 
 
Fertility 
There are no data concerning human fertility. A study in female rabbits did not indicate reproductive 
or developmental toxicity of Foclivia. Male fertility has not been assessed in animals (see section 5.3).  
 
4.7 Effects on ability to drive and use machines 
 
Some of the effects mentioned under section 4.8  may affect the ability to drive 
or use machines. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
 
• Clinical trials 
 
Adverse reactions from clinical trial in adults and elderly (above 18 years old) 
The incidence of adverse reactions has been evaluated in seven clinical trials in healthy subjects 
involving over 4300 adults and elderly receiving H5N1 vaccine combined with MF59C.1 adjuvant (at 
least 7.5 µg haemagglutinin, HA) containing either the A/turkey/Turkey/1/2005 or the 
A/Vietnam/1194/2004 strain. There were 3872 subjects 18-60 years of age, 365 subjects 61-70 years 
of age, and 89 subjects greater than 70 years of age. The safety profile across clinical trials using 
H5N1 vaccine containing either the A/turkey/Turkey/1/2005 or the A/Vietnam/1194/2004 strain is 
comparable (see section 5.1). Clinical trials in 80 subjects receiving adjuvanted vaccine with an H5N3 
or an H9N2 strain showed a similar safety profile. 
 
Across all trials, there was a general trend towards decreased reports of solicited local adverse 
reactions after the second vaccination compared with the first.  
 
Irrespective of antigen dose, almost all solicited systemic adverse reactions were reported on the day 
of vaccination (day 1) or during the 3 days immediately following. 
 
Data on safety of a booster dose are limited to three trials performed with H5N1 MF59C.1 adjuvanted 
vaccine containing A/Vietnam/1194/2004 (V87P1, V87P2) or A/turkey/Turkey/1/2005 (V87P1E1) 
that included 116 adults (18-60 years) and 56 elderly subjects (≥61 years). No increase in solicited 
adverse reactions was reported when a booster dose was administered 6 or 18 months after the initial 
dosing series. A slight increase in solicited adverse reactions in adults was reported when a booster 
dose was administered 18 months after the initial dosing series. In the elderly, the reported solicited 
adverse reactions increased with the third booster dose only when compared with the second dose. 
 
Tabulated list of adverse reactions 
 
The adverse reaction rates reported after any vaccination dose (i.e. 1st, 2nd or booster) were similar 
and are listed according to the following MedDRA frequency convention and system organ class: 
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). 
 

MedDRA System 
Organ class 

Very common 
(≥1/10) 

Common 
(≥1/100 to <1/10) 

Rare 
(≥1/10,000 to 
˂1/1,000) 

Nervous system 
disorders 

Headache   



42 

Gastrointestinal 
disorders 

 Nausea  

Skin and 
subcutaneous tissue 
disorders 

 Sweating  

Musculoskeletal 
and connective 
tissue disorders 

Myalgia Arthralgia  

General disorders 
and administration 
site conditions 

Injection site 
swelling, Injection 
site pain, Injection 
site induration, 
Injection site redness, 
Fatigue, Chills, 
Malaise 

Injection site 
ecchymosis, Fever  

Anaphylaxis 

 
The majority of these reactions usually disappear within 1-2 days without treatment. 
 
Clinical trials in special populations 
 
Adverse reactions in special populations have been evaluated in two clinical trials, V87_25 and 
V87_26, involving adult (18-60 years) and elderly (≥ 61 years) subjects who were either healthy or 
with underlying medical conditions or immunosuppressive conditions. 
 
 H5N1 MF59C.1 adjuvanted A/turkey/Turkey/1/2005 vaccine 
 Study V87_25 Study V87_26 
 Medical conditions Healthy Immunocompromi

sed Healthy 

 
Adults 
(20-60 
years)* 

Elderly 
(61-84 
years)* 

Adults 
(19-60 
years)* 

Elderly 
(61-79 
years)* 

Adults 
(20-60 
years)* 

Elderly 
(61-84 
years)* 

Adults 
(18-59 
years)* 

Elderly 
(61-91 
years)*  

No. of 
subjects N=145 N=149 N=59 N=58 N=147 N=148 N=58 N=62 

*actual age range of population enrolled 
 
Across studies V87_25 and V87_26, the safety of H5N1 A/turkey/Turkey/1/2005 in healthy adult and 
elderly subjects was consistent with existing safety data from previous clinical trials. However, in 
immunocompromised subjects 18 through 60 years of age, slightly higher rates of nausea (13.0%) 
were reported. In addition, higher rates of arthralgia (up to 23.3%) were reported in both adult and 
elderly subjects, who were immunocompromised or with underlying medical conditions. 
 
The following solicited adverse reactions were additionally collected in these two studies and reported 
with the following frequencies across subjects who received H5N1 A/turkey/Turkey/1/2005 
irrespective of age or health status: diarrhoea (up to 11.9%), loss of appetite (up to 10.9%) and 
vomiting (up to 1.7%). In both studies, subjects with underlying medical and immunosuppressive 
conditions reported higher frequencies of diarrhoea, loss of appetite and vomiting compared to healthy 
subjects (irrespective of age).    
 
Adverse reactions from clinical trial in children aged 6 months to 17 years 
A clinical trial (Study V87P6) was conducted with a H5N1 A/Vietnam/1194/2004 vaccine combined 
with MF59C.1 adjuvant (N=334) vs seasonal influenza vaccine (N=137). 
 
Regardless of age, reactogencity was higher after the first dose than after the second vaccination. 
Reactogenicity after the third dose, administered 12 months following the second dose, was higher 
than after both first and second doses. The percentages of subjects reporting local adverse reactions 



43 

were higher in the older age groups, mainly due to the higher reports for pain. In toddlers, erythema 
and tenderness were the most frequently reported solicited local adverse reactions; irritability and 
unusual crying were the most frequently reported solicited systemic adverse reactions. In children and 
adolescents, pain was the most frequently reported solicited local adverse reaction, and fatigue and 
headache were the most frequently reported solicited systemic adverse reactions. Across all ages, the 
frequency of fever after any dose was not more than 6%.  
 

 Study V87P6 
H5N1 MF59C.1 adjuvanted A/Vietnam/1194/2004 vaccine 

 First dose 
Second 

dose (21 days after 
first dose) 

Third dose 
(12 months after 

second dose) 
Toddlers (6 to 

35 months) 
N=145 N=138 N=124 

Any 76% 68% 80% 
Local 47% 46% 60% 
Systemic 59% 51% 54% 
Fever ≥ 38°C (≥ 40°C) 0% 0% 0%  
Any Other Adverse 
Event 

54% 49% 35% 

Children (3 to 8 years) N=96 N=93 N=85 
Any 72% 68% 79% 
Local 66% 58% 74% 
Systemic 32% 33% 45% 
Fever ≥ 38°C (≥ 40°C) 4%  2%  6%  
Any Other Adverse 
Event 

36% 31% 19% 

Adolescents(9 to 
17 years) 

N=93 N=91 N=83 

Any 91% 82% 89% 
Local 81% 70% 81% 
Systemic 69% 52% 69% 
Fever ≥ 38°C (≥ 40°C) 0%  1%  2%  
Any Other Adverse 
Event 

30% 27% 22% 

 
Focetria (an MF59.1 adjuvanted H1N1 pandemic vaccine similar to Foclivia). 
 
Adverse reactions in the week following vaccination with Focetria H1N1v from 77 children 3-8 years 
old and 80 children and adolescents 9-17 years old receiving the 7.5 µg formulation were reported as 
follows: 
 

 Injection 1 Injection 2 
Children (3 to 8 years of age) N= 77 N= 75 

Any adverse reaction  74%  69% 
Local  62%  56% 
Systemic  39%  35% 
Fever ≥ 38°C to 38.9°C  4% 1% 
Fever 39°C to 39.9°C 0% 1% 
Fever ≥ 40° C 0% 0% 
Any other AE  14%  17% 
Adolescents (9 to 17 years of age) N= 80 N= 79 

Any adverse reaction  79%  66% 
Local  70%  58% 
Systemic  45%  30% 



44 

Fever ≥ 38°C to 38.9°C  3% 1% 
Fever 39°C to 39.9°C 0% 0% 
Fever ≥ 40° C 0% 0% 
Any other AE  13%  10% 

 
Data in children and adolescents 3-17 years suggest a slight decrease in reactogenicity after the second 
dose, with no increase in rates of fever. 
 
Very common reactions reported in children and adolescents 3 to 17 years of age: 
Pain, induration and erythema, malaise, myalgia, headache and fatigue. 
 
Adverse reactions in the week following vaccination with Focetria H1N1v from 
73 infants 6-11 months old and 73 toddlers 12-35 months old, receiving the 7.5 µg formulation were 
reported as follows: 
 

 Injection 1 Injection 2 
Infants (6 to 11 months of age) N= 73 N= 68 

Any adverse reaction 79% 65% 
Local 44%  26% 
Systemic  70%  56% 
Fever ≥ 38°C to 38.9°C   11%  9% 
Fever 39°C to 39.9°C  3% 4% 
Fever ≥ 40° C 0% 0% 
Any other AE  32%  31% 
Toddlers (12 to 35 months of age) N= 73 N= 71 

Any adverse reaction 70%  71% 
Local  51%  49% 
Systemic  60%  49% 
Fever ≥ 38°C to 38.9°C  10% 11% 
Fever 39°C to 39.9°C 4% 1% 
Fever ≥ 40° C 1% 0% 
Any other AE 21%  24% 

 
Data in infants and toddlers 6-35 months of age suggest a slight decrease in reactogenicity after the 
second dose, with no increase in rates of fever. 
 
Very common reactions reported in 146 infants and toddlers 6 to 35 months of age: 
Tenderness, erythema, irritability, unusual crying, sleepiness, diarrhoea, vomiting and change in eating 
habits. Induration and ecchymosis were very common reactions in toddlers but were less common in 
infants. 
 
• Post-marketing surveillance 
 
No post-marketing surveillance data are available following Foclivia administration. 
 
The following adverse events were reported from post-marketing surveillance with Focetria (an H1N1 
pandemic vaccine similar to Foclivia) which contains the same amount of adjuvant MF59C.1 as 
Foclivia, approved for use in children 6 months of age and above, adults and the elderly: 
 
Blood and lymphatic system disorders 
Lymphadenopathy. 
 
Immune system disorders 
Allergic reactions, anaphylaxis including dyspnoea, bronchospasm, laryngeal oedema, in rare cases 
leading to shock, angioedema. 



45 

 
Nervous system disorders 
Headache, dizziness, somnolence, syncope. Neurological disorders, such as neuralgia, paraesthesia, 
convulsions and neuritis. 
 
Cardiac disorders 
Palpitation, tachycardia. 
 
Respiratory disorders 
Cough. 
 
Gastrointestinal disorders 
Gastrointestinal disorders such as nausea, vomiting, abdominal pain and diarrhoea.  
 
Skin and subcutaneous tissue disorders 
Generalised skin reactions including pruritus, urticaria or non-specific rash. 
 
Musculoskeletal, connective tissue and bone disorders 
Muscular weakness, pain in extremities. 
 
General disorders and administration site conditions 
Asthenia. 
 
The following additional adverse events were reported from post-marketing surveillance with seasonal 
non-adjuvanted trivalent vaccines in all age groups and a seasonal trivalent MF59-adjuvanted subunit 
influenza vaccine approved for use in elderly subjects 65 years of age and older: 
 
Blood and lymphatic system disorders 
Thrombocytopenia (in some cases reversible platelet counts less than 5000 mm3). 
 
Nervous system disorders 
Neurological disorders, such as encephalomyelitis  and Guillain Barré syndrome. 
 
Vascular disorders 
Vasculitis which may be associated with transient renal involvement. 
 
Skin and subcutaneous tissue disorders 
Erythema multiforme. 
 
General disorders and administration site conditions 
Extensive swelling of injected limb lasting more than one week, injection-site cellulitis-like reaction 
(some cases of swelling, pain, and redness extending more than 10 cm and lasting more than 1 week). 
 
This medicinal product contains thiomersal (an organomercuric compound) as a preservative and 
therefore, it is possible that sensitisation reactions may occur (see section 4.4). 
 
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 Appendix V 
 
4.9 Overdose 
 
No case of overdose has been reported. 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


46 

5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Influenza vaccine, ATC Code: J07BB02 
 
Clinical efficacy and safety 
 
Pandemic preparedness 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 a pandemic preparedness vaccine will support a vaccination strategy that is likely to be 
used for the pandemic vaccine: clinical efficacy and safety data obtained with pandemic preparedness 
vaccines are relevant for the pandemic vaccines. 
 
Immune response to H5N1 vaccine combined with MF59C.1 adjuvant containing 
A/Vietnam/1194/2004 or A/turkey/Turkey/1/2005 strain. 
 
Adults (18-60 years) 
 
A Phase II clinical trial (V87P1) was conducted with  H5N1  MF59C.1 adjuvanted vaccine containing 
A/Vietnam/1194/2004 in 312 healthy adults. Two doses of vaccine containing  7.5 µg 
Haemagglutinin(HA)/dose were administered three weeks apart to 156 subjects. Immunogenicity was 
assessed in 149 subjects. 
 
In a phase III clinical trial  (V87P13), 2693  adult subjects were enrolled and 2566 received two doses 
of H5N1 MF59C.1 adjuvanted vaccine containing A/Vietnam/1194/2004 7.5 µg  HA/dose 
administered three weeks apart. Immunogenicity was assessed in a subset (N=197) of subjects. 
 
In a third clinical trial (V87P11) 194 adult subjects received two doses of H5N1 MF59C.1 adjuvanted 
vaccine containing A/turkey/Turkey/1/2005 7.5 µg  HA/dose administered three weeks apart. 
Immunogenicity was assessed in 182 subjects. 
 
The seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA 
antibody to H5N1 A/Vietnam/1194/2004 and to H5N1 A/turkey/Turkey/1/2005 in the adults measured 
by Single Radial Haemolysis (SRH) assay was as follows: 
 

Anti-HA antibody 
(SRH) 

Study V87P1 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=149 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=197 

Study V87P11 
A/turkey/Turkey/1/2005 

21 days after 2nd dose 
N=182 

Seroprotection rate 
(95%CI)* 85% (79-91) 91% (87-95) 91% (85-94) 

Seroconversion rate 
(95%CI)** 85% (78-90) 78% (72-84) 85% (79-90) 

Seroconversion factor 
(95%CI)*** 7.74 (6.6-9.07) 4.03 (3.54-4.59) 6 (5.2-6.93) 

 

Anti-HA antibody (SRH) 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=69 

Study V87P13 
A/Vietnam/1194/2004 
21 days after 2nd dose 

N=128 

- 

Baseline Serostatus < 4 mm2 ≥ 4 mm2 - 
Seroprotection rate 
(95%CI)* 87% (77-94) 94% (88-97) - 

Seroconversion rate 
(95%CI)** 87% (77-94) 73% (65-81) - 



47 

Seroconversion factor 
(95%CI)*** 8.87 (7.09-11) 2.71 (2.38-3.08) - 

* Seroprotection: SRH area ≥25 mm2 
** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 

area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** geometric mean ratios (GMRs) of SRH 
 
MicroNeutralization (MN) results against A/Vietnam/1194/2004 (Studies V87P1 and 
V87P13) indicate a seroprotection and seroconversion rate ranging from 67% (60-74) to 85% (78-90) 
and 65% (58-72) to 83% (77-89), respectively. Immune response to vaccination assessed by MN assay 
is in line with results obtained with SRH. 
 
In Study V87P11 MN results against homologous A/turkey/Turkey/1/2005 indicate a seroprotection 
and seroconversion rate of 85% (79-90) and 93% (89-96), respectively. Immune response to 
vaccination assessed by MN assay is in line with results obtained with SRH. 
 
Persistence of antibodies after primary vaccination in this population was assessed by 
Hemagglutination Inhibition (HI), SRH, and MN assays. Compared to the antibody levels obtained 
at day 43 after completion of primary vaccination schedules, antibody levels at day 202 were reduced 
by 1/5 to 1/2 from their prior levels. 
 
Elderly (≥61 years) 
 
The seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA 
antibody to H5N1 MF59C.1 adjuvanted vaccine (A/Vietnam/1194/2004 and A/turkey/Turkey/1/2005) 
in subjects aged 61 years and older (limited number of subjects were above 70 years of age; N=123) 
measured by SRH assay assessed in two clinical studies were as follows: 
 

Anti-HA antibody (SRH) 

Study V87P1 
A/Vietnam/1194/2004 

21 days after 2nd dose 
N=84a 

Study V87P13 
A/Vietnam/1194/2004 

21 days after 2nd dose 
N=210b 

Study V87P11 
A/turkey/Turkey/1/2005 

21 days after 2nd dose 
N=132c 

Seroprotection rate 
(95%CI)* 80% (70-88) 82% (76-87) 82% (74-88) 

Seroconversion rate 
(95%CI)** 70% (59-80) 63% (56-69) 70% (61-77) 

Seroconversion factor 
(95%CI)*** 4.96 (3.87-6.37) 2.9 (2.53-3.31) 3.97 (3.36-4.69) 

 

Anti-HA antibody (SRH) 

Study V87P13 
A/Vietnam/1194/2004 

21 days after 2nd dose 
N=66 

Study V87P13 
A/Vietnam/1194/2004 

21 days after 2nd dose 
N=143 

Baseline Serostatus < 4 mm2 ≥ 4 mm2 
Seroprotection rate (95%CI)* 82% (70-90) 82% (75-88) 
Seroconversion rate (95%CI)** 82% (70-90) 54% (45-62) 
Seroconversion factor (95%CI)*** 8.58 (6.57-11) 1.91 (1.72-2.12) 

a  Ages 62-88 years; b Ages 61-68 years; c Ages 61-89 years 
* Seroprotection: SRH area ≥25 mm2 
** Seroconversion was defined as an SRH area ≥25mm2 for subjects who were seronegative at baseline (Day 1 SRH 

area ≤4mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
 
MN results against A/Vietnam/1194/2004 (Studies V87P1 and V87P13) indicate a seroprotection and 
seroconversion rate ranging from 57% (50-64) to 79% (68-87) and 55% (48-62) to 58% (47-69) 
respectively. MN results, similar to SRH results, demonstrated strong immune response after 
completion of priming vaccination series in a population of elderly subjects. 
 



48 

In Study V87P11, MN results against homologous A/turkey/Turkey/1/2005 indicate a seroprotection 
and seroconversion rate of 68% (59-75) and 81% (74-87), respectively. Immune response to 
vaccination assessed by MN assay is similar to SRH results. 
 
Persistence of antibodies after primary vaccination in this population as assessed by HI, SRH, and MN 
tests reduced from 1/2 to 1/5 of their post-vaccination level at day 202 as compared to day 43 after 
completion of primary schedules as assessed by HI, SRH, and MN tests. Up to 50% (N=33) of the 
elderly subjects aged 62 to 88 years immunised with H5N1  MF59C.1 adjuvanted vaccine containing 
A/Vietnam/1194/2004 in trial V87P1 were seroprotected at six months. 
 
A third (booster) dose of H5N1 vaccine combined with MF59C.1 was administered 6 months after the 
primary vaccination series. Results are shown by SRH. 
 
The seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA 
antibody to H5N1 A/Vietnam/1194/2004 measured by SRH assays were as follows: 
 

 
Study V87P1 Adults 

A/Vietnam/1194/2004 
booster after 2nd dose 

Study 
V87P2 Adults 

A/Vietnam/1194/
2004 

booster after 2nd 
dose 

Study V87P1 Elderly 
A/Vietnam/1194/2004 
booster  after 2nd dose 

SRH N=71 N=13 N=38 
Seroprotection rate 
(95%CI)* 89% (79-95) 85% (55-98) 84% (69-94) 

Seroconversion rate 
(95%CI)** 83% (72-91) 69% (39-91) 63% (46-78) 

Seroconversion factor (9
5%CI)*** 5.96 (4.72-7.53) 2.49 (1.56-3.98) 5.15 (3.46-7.66) 

* Seroprotection: SRH area ≥25 mm2 
** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 

area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
 
• Supportive data in adult and elderly populations 
 
In two dose finding studies 80 adults received an adjuvanted pandemic preparedness vaccine (H5N3 or 
H9N2). 
 
Two doses of vaccine with H5N3 (A/Duck/Singapore/97) strain at 3 different dosages 
(7.5, 15 and 30 µg HA/dose) were administered three weeks apart. 
 
Serum samples were tested against the original H5N3 and also a number of H5N1 isolates. 
 
Serologic responses obtained with the SRH assay showed that 100% of subjects achieved 
seroprotection and 100% seroconverted after two 7.5 µg injections. The adjuvanted vaccine was also 
found to induce antibodies that cross-protected against the H5N1 strains isolated in 2003 and 2004, 
which exhibit some antigenic drift compared to the original strains. 
 
Two doses of vaccine containing H9N2 (A/chicken/Hong Kong/G9/97) strain at 4 different dosages 
(3.75, 7.5, 15 and 30 µg HA/dose), were administered four weeks apart. Serologic responses obtained 
with the HI assay showed that 92% of subjects achieved seroprotection and 75% seroconverted after 
two 7.5 µg injections. 
 
Cross reactivity 
 



49 

Cross-reactive immune response elicited by H5N1 A/Vietnam/1194/2004 against 
A/turkey/Turkey/1/2005 and A/Indonesia/5/2005 

 
Adults (18-60 years) 
 
Some heterologous immune response against A/turkey/Turkey/1/2005 (NIBRG23; clade 2.2.1) and 
A/Indonesia/5/2005 (clade 2.1) was detectable both after the second and third vaccinations, indicating 
cross-reactivity of the clade 1 vaccine against clade 2 strains. 
 
Seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA antibodies 
to H5N1 A/turkey/Turkey/1/2005 after the 2nd dose in adults 18-60 years of age, measured by SRH 
and HI assays were as follows: 
 

 Anti-HA 
antibody 

Study V87P1 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose  
N=70 

Study V87P12 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose 
N=60 

Study V87P3 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose 
N=30 

Study V87P13 
A/Vietnam/1194/

2004 
21 days after 2nd 

dose 
N=197 

SR
H 

Seroprotectio
n rate 
(95%CI)* 

70% (58-80) 65% (52-77) 90% (73-98) 59% (52-66) 

Seroconversio
n rate 
(95%CI)** 

NAǂ 65% (52-77) 86% (68-96) 49% (42-56) 

Seroconversio
n 
factor(95%CI)
*** 

NAǂ 4.51 (3.63-5.61) 7.67 (6.09-9.67) 2.37 (2.1-2.67) 

  N=69 N=60 N=30 N=197 
HI Seroprotectio

n rate 
(95%CI)° 

36% (25-49) 28% (17-41) 24% (10-44) 23% (18-30) 

Seroconversio
n rate 
(95%CI)° 

NAǂ 28% (17-41) 21% (8-40) 19% (14-25) 

Seroconversio
n factor 
(95%CI)°° 

NAǂ 2.3 (1.67-3.16) 1.98 (1.22-3.21) 1.92 (1.64-2.25) 

* Seroprotection: SRH area ≥25 mm2 

** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 
area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
ǂ In V87P1: baseline not tested 
° measured by HI assay ≥40 
°° GMRs of HI 
 
MN results for the clinical studies V87P12, V87P3 and V87P13 in the Table above revealed a 
seroprotection rate and seroconversion rate against A/turkey/Turkey/2005 ranging from 10% (2-27) 
to 39% (32-46) and 10% (2-27) to 36% (29-43) respectively. MN results yielded a GMR against 
A/turkey/Turkey/2005 ranging from 1.59 to 2.95. 
 
Elderly (≥61 years) 
 
Seroprotection rate*, seroconversion rate* and the seroconversion factor** for anti-HA antibodies 
to H5N1 A/turkey/Turkey/05 after the 2nd dose in elderly subjects ≥61 years of age, measured by SRH 
and HI assays were as follows: 



50 

 

 Anti-HA antibody 

Study V87P1 
A/Vietnam/1194/2004 
 
21 days after 2nd dose 
N=37 

Study V87P13 
A/Vietnam/1194/2004 
 
21 days after 2nd dose 
N=207 

SRH 
Seroprotection rate (95%CI)* 57% (39-73) 20% (18-23) 
Seroconversion rate (95%CI)* NA*** 48% (41-55) 
Seroconversion factor (95%CI)** NA*** 1.74 (1.57-1.94) 

  N=36 N=208 

HI 
Seroprotection rate (95%CI)° 36% (21-54) 25% (19-32) 
Seroconversion rate (95%CI)° NA*** 19% (14-25) 
Seroconversion factor (95%CI)°° NA*** 1.79 (1.56-2.06) 

* measured by SRH assay ≥25 mm2 
** geometric mean ratios of SRH 
° measured by HI assay ≥40 
°° geometric mean ratios of HI 
*** In V87P1: baseline not tested 
 
MN results for the clinical studies in the Table above revealed a seroprotection rate against 
A/turkey/Turkey/05 ranging from 11% (3-25) (study V87P1) to 30% (24-37) (study V87P13) and 
seroconversion rate of 25% (19-31) for study V87P13. MN results in study V87P13 yielded a GMR 
against A/turkey/Turkey/05 of 2.01 (1.78-2.26). 
 

Cross-reactive immune response elicited by A/turkey/Turkey/1/2005 against 
A/Indonesia/5/2005 and A/Vietnam/1194/2004 

 
Heterologous immune response against A/Indonesia/5/2005 (clade 2.1) was detectable in Study 
V87P11 after the second vaccination, indicating cross-reactivity of the clade 2.2.1 vaccine against 
clade 2.1 strains. 
 
Seroprotection rate*, seroconversion rate** and the seroconversion factor*** for anti-HA antibodies 
to H5N1 A/Indonesia/5/2005 and A/Vietnam/1194/2004 after the 2nd dose in adults (18-60 years) and 
elderly (> 61years), measured by SRH and HI assays were as follows: 
 

Anti-HA 
antibody 

 V87P11 Adults (18-60 years) 
N=186 

V87P11 Elderly (>61-89 years)a 
N=142 

  A/Indonesia/ 
5/2005 

A/Vietnam/ 
1194/2004 

A/Indonesia/ 
5/2005 

A/Vietnam/ 
1194/2004 

SRH Seroprotection 
rate (95%CI)* 

83 
(77-88) 

62 
(54-69) 

61 
(52-69) 

45 
(37-54) 

 Seroconversion 
rate (95%CI)** 

79 
(72-85) 

60 
(53-68) 

64 
(56-73) 

44 
(35-53) 

 Seroconversion 
factor 
(95%CI)*** 

6.24 
(5.44-7.16) 

4.45 
(3.85-5.14) 

3.87 
(3.31-4.53) 

3.03 
(2.56-3.58) 

  N=194 N=148 
HI Seroprotection 

rate (95%CI) ° 
50 

(43-57) 
47 

(40-55) 
34 

(26-42) 
39 

(31-48) 
 Seroconversion 

rate (95%CI) ° 
49 

(42-56) 
44 

(37-51) 
32 

(25-41) 
34 

(26-42) 
 Seroconversion 

factor (95%CI) °° 
4.71 

(3.74-5.93) 
4.25 

(3.36-5.37) 
2.69 

(2.18-3.32) 
2.8 

(2.2-3.55) 



51 

a  actual age range of population enrolled 
* Seroprotection: SRH area ≥25 mm2 

** Seroconversion was defined as an SRH area ≥25 mm2 for subjects who were seronegative at baseline (Day 1 SRH 
area ≤4 mm2) or a significant (at least 50%) increase in SRH area for subjects who were seropositive at baseline (Day 
1 SRH area >4 mm2) 

*** GMRs of SRH 
° measured by HI assay ≥40 
°° GMRs of HI 
 
MN results for A/Indonesia/5/2005 revealed a seroprotection rate of 38% (31-45) in adults 
(18-60 years) and 14% (8-20) in elderly (>61 years); a seroconversion rate of 58% (50-65) in adults 
and 30% (23-38) in elderly and finally a GMR of 4.67 (3.95-5.56) in adults and 2.19 (1.86-2.58) 
in elderly. 
 
MN results for A/Vietnam/1194/2004 revealed a seroprotection rate of 10% (6-16) in adults 
(18-60 years) and 6% (3-11) in elderly (>61 years); a seroconversion rate of 19% (13-25) in adults 
and 7% (4-13) in elderly and finally a GMR of 1.86 (1.63-2.12) in adults and 1.33 (1.17-1.51) 
in elderly. 
 
Long term booster immune memory: 
 
A single vaccination with H5N1 MF59C.1 adjuvanted A/Vietnam/1194/2004 vaccine induced high 
and rapid serological response in subjects primed 6-8 years previously with two doses of a different 
vaccine, having the same formulation but using the H5N3 strain. 
 
In a phase I clinical trial (V87P3) adult subjects aged 18-65 years primed 6-8 years previously with 
2 doses of MF59-adjuvanted H5N3 vaccine/A/Duck/Singapore/97, were administered 2 booster doses 
of  H5N1 MF59C.1 adjuvanted A/Vietnam/1194/2004 vaccine. SRH results after the first dose, that 
mimic prepandemic priming plus single heterologous booster dose, revealed seroprotection and 
seroconversion rates of 100% (74- 100) and an 18-fold increase in SRH area (GMR). 
 
Alternative vaccination schedules: 
 
In a clinical trial evaluating 4 different vaccination schedules in 240 subjects 18 to 60 years of age, 
where the second dose occurred either 1, 2, 3 or 6 weeks after the first dose of H5N1 MF59C.1 
adjuvanted A/Vietnam/1194/2004 vaccine, all vaccine schedule groups after 3 weeks from the 2nd 
vaccination achieved high levels of antibodies as evaluated with SRH. SRH seroprotection rates 
ranged from 86% to 98%, seroconversion rates from 64% to 90%, and GMR ranged from 2.92 to 4.57. 
The magnitude of immune response was lower in the group who received the 2nd dose 1 week later and 
higher in the groups with longer interval schedules. 
 
Subjects with underlying medical or immunosuppressive conditions: 
 
Immunogenicity of H5N1 A/turkey/Turkey/1/2005 in adults (18 to 60 years) and elderly (>61 years) 
subjects with underlying medical conditions (Study V87_25) or immunosuppressive conditions 
(mainly HIV-infected subjects) (Study V87_26) in comparison to healthy adults (18-60 years) and 
elderly (>61 years), was evaluated in two randomised, phase III controlled clinical trials (with a 
seasonal trivalent inactivated MF59-adjuvanted subunit influenza vaccine approved for use in elderly 
subjects 65 years of age and older as a comparator). In trial V87_25 and V87_26, 96 and 67 subjects, 
respectively, were over the age of 70 years. In both trials, immunogenicity of 
H5N1 A/turkey/Turkey/1/2005 was shown by HI, SRH and MN assays following both the first and 
second dose.  
 
Geometric mean area*, seroprotection rate*, seroconversion rate* and the seroconversion factor** for 
anti-HA antibody to H5N1 A/turkey/Turkey/1/2005 measured by SRH assays 21 days after the 2nd 
dose were as follows: 
 
 



52 

a  actual age range of population enrolled 
*  measured by SRH assay seroprotection: SRH area ≥25 mm2, seroconversion: SRH area ≥25 mm2 for subjects with a 

baseline SRH area ≤4 mm2 or a minimum 50% increase in SRH area for subjects with >4 mm2. 
** geometric mean ratios of SRH 

 
HI results for the two clinical studies revealed lower values than those reported in previous studies. 
Seroconversion rates against homologous A/turkey/Turkey/1/2005 ranged from 37.50% to 43.10% in 
healthy adults, and from 19.18% to 26.47% in adults with immunosuppressive or underlying medical 
conditions, respectively; seroconversion rates ranged from 21.43% to 30.65% in healthy elderly 
subjects, and from 24.49% to 27.86% in elderly subjects with immunosuppressive or underlying 
medical conditions. Similar trends were observed for seroprotection rates in both studies. 
 
MN results against homologous A/turkey/Turkey/1/2005 indicate a seroconversion rate of 66.67% in 
healthy adults, and ranging from 33.57% to 54.14% in adults with immunosuppressive or underlying 
medical conditions, respectively; seroconversion rates ranged from 24.39% to 29.03% in healthy 
elderly subjects, and from 31.65% to 39.42% in elderly subjects with immunosuppressive or 
underlying medical conditions. Similar trends were observed for seroprotection rates in both studies. 
 
In both studies V87_25 and V87_26, the lower levels of antibodies (as measured by HI, SRH and MN 
assays) and reduced seroprotection rates in adults and elderly (≥ 61 years old) subjects with underlying 
medical or immunosuppressive conditions, suggest that H5N1 A/turkey/Turkey/1/2005 may not elicit 
the same level of protection against A/H5N1 strain as compared to healthy adults (see section 4.4). 
These studies provided limited immunogenicity data in subjects with some underlying medical (in 
particular, renal impairment and peripheral cardiovascular disease) and immunosuppressive conditions 
(in particular, transplant recipients and patients under cancer treatment). In these trials, lower levels of 
antibodies and reduced seroprotection rates against homologous H5N1 A/turkey/Turkey/1/2005 were 
also measured in healthy elderly subjects, as compared to healthy adults, though previous studies 

Study V87_25 

 
Adults 

 (20- 60 years)a  
Adults  

(19- 60 years)a 
Elderly  

(61-84 years)a 
 

Elderly 
(61-79 years)a 

 

Anti-HA antibody 
(SRH) 

Medical 
Conditions 

N=140 

Healthy 
N=57 

Medical 
Conditions 

N=143 

Healthy 
N=57 

Geometric Mean 
Area (95%CI)* 

31.07 
(27.43-35.19) 

58.02 
(48.74-69.06) 

29.34 
(26.07-33.01) 

27.78 
(22.57-34.18) 

Seroprotection rate 
(95%CI)* 

65.00 
(56.5-72.9) 

89.47 
(78.5-96) 

58.74 
(50.2-66.9) 

57.89 
(44.1-70.9) 

Seroconversion rate 
(95%CI)* 

72.86 
(64.7-80) 

98.25 
(90.6-99.96) 

64.34 
(55.9-72.2) 

66.67 
(52.9-78.6) 

Seroconversion 
factor (95%CI)** 

3.33 
(2.94-3.77) 

6.58 
(5.53-7.83) 

2.37 
(2.10-2.66) 

2.96 
(2.41-3.64) 

Study V87_26 

 
Adults  

(20- 60 years)a   
Adults 

(18-59 years)a 
Elderly  

(61-84 years)a 
 

Elderly  
(61-91 years)a 

 

Anti-HA antibody 
(SRH) 

Immuno- 
compromised 

N=143 

Healthy 
N=57 

Immuno- 
compromised 

N=139 

Healthy 
N=62 

Geometric Mean 
Area (95%CI)* 

26.50 
(22.49-31.22) 

48.58 
(40.01-58.99) 

26.85 
(23.01-31.33) 

23.91 
(18.89-30.26) 

Seroprotection rate 
(95%CI)* 

60.84 
(52.3-68.9) 

87.72 
(76.3-94.9) 

58.99 
(50.3-67.3) 

53.23 
(40.1-66) 

Seroconversion rate 
(95%CI)* 

61.54 
(53-69.5) 

89.47 
(78.5-96) 

64.75 
(56.2-72.7) 

56.45 
(43.3-69) 

Seroconversion 
factor (95%CI)** 

3.16 
(2.69-3.73) 

7.10 
(5.85-8.62) 

3.15 
(2.70-3.68) 

2.83 
(2.24-3.58) 



53 

showed induction of sufficiently immunogenic responses against H5N1 strains (see above for 
information on elderly). 
 

Available data in paediatric populations 
 
A clinical trial (V87P6) was conducted with a H5N1 A/Vietnam/1194/2004 vaccine combined with 
MF59C.1 adjuvant in 471 children from 6 months to 17 years of age. Two doses of 7.5 µg were 
administered three weeks apart and a third dose 12 months following the first dose. After 3 weeks 
from the 2nd vaccination (day 43) all age groups (i.e. 6-35 months, 3-8 years and 9-17 years) achieved 
high levels of antibodies to A/Vietnam/1194/2004 as evaluated with SRH and HI assays as presented 
in table below. In this trial no vaccine related SAEs were observed. 
 

 Toddlers  
(6 to 35 months) 

Children  
(3 to 8 years) 

Adolescents  
(9 to 17 years) 

N=134 N=91 N=89 

HI 

Seroprotection rate 
(95% CI) 
Day 43 

97% 
(92-99) 

97% 
(91-99) 

89% 
(80-94) 

Seroconversion 
factor (95% CI) 
Day 43 to Day 1 

129 
(109-151) 

117 
(97-142) 

67 
(51-88) 

Seroconversion 
rate (95% CI) 

Day 43 

97% 
(92-99) 

97% 
(91-99) 

89% 
(80-94) 

SRH 

 N=133 N=91 N=90 
Seroprotection rate 

(95% CI) 
Day 43 

100% 
(97-100) 

100% 
(96-100) 

100% 
(96-100) 

Seroconversion 
factor (95% CI) 
Day 43 to Day 1 

16 
 (14-18) 

15 
 (13-17) 

14 
 (12-16) 

Seroconversion 
rate (95% CI) 

Day 43 

98% 
(95-100) 

100% 
(96-100) 

99% 
(94-100) 

 
MN results against a A/Vietnam/1194/2004 indicate a seroprotection rate of 99% (95%CI: 94-100), 
a seroconversion rate ranging from 97% (95%CI: 91-99) to 99% (95%CI: 96-100) and a GMR ranging 
from 29 (95%CI: 25-35) to 50 (95%CI: 44-58). 
 
Immunogenicity results with Focetria H1N1v (Study V111_03): 
The seroprotection rate and seroconversion rate measured by HI assay and the seroconversion factor 
expressed as geometric mean ratio of HI for anti-HA antibody to H1N1 after administration of one and 
two 7.5 µg doses of Focetria was evaluated in 70 children and adolescents (9-17 years), 60 children 
(3-8 years), 58 children (12-35 months) and 49 infants (6-11 months). CHMP immunogenicity criteria 
set for adults (18-60 years) were met both after the 1st and the 2nd dose in all the above age strata (both 
in the overall population and in the subset seronegative at baseline). 
 
The European medicines Agency has deferred the obligation to submit the results of studies with 
Foclivia in one or more subsets of the paediatric populations in active immunisation against 
H5N1 subtype of Influenza A virus. See section 4.2 for information on paediatric use. 
 
Foclivia 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. 
 



54 

5.2 Pharmacokinetic properties 
 
Not applicable. 
 
5.3 Preclinical safety data 
 
Non-clinical data obtained with Foclivia and with seasonal influenza vaccine containing 
MF59C.1 adjuvant reveal no special hazard for humans based on conventional studies of repeated 
dose toxicity, local tolerance, female fertility, and reproductive and developmental toxicity (through 
the end of the lactation period). 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride, 
Potassium chloride, 
Potassium dihydrogen phosphate, 
Disodium phosphate dihydrate, 
Magnesium chloride hexahydrate, 
Calcium chloride dihydrate, 
Thiomersal, 
Water for injections. 
 
For the adjuvant, see section 2. 
 
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. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. Discard if the vaccine has been frozen. Store in the 
original package in order to protect from light. 
 
6.5 Nature and contents of container 
 
5.0 ml in 10-dose vial (type I glass) with stopper (halo-butyl rubber). Packs of 10. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Gently shake the multidose vial each time before withdrawing a dose (0.5 ml) of the vaccine into a 
syringe. After shaking, the normal appearance of Foclivia is a milky-white suspension. 
Visually inspect the suspension prior to administration. In case of any particles and/or abnormal 
appearance, the vaccine should be discarded. 
 
Although Foclivia in multidose vials contains a preservative that inhibits microbial growth, 
minimisation of the risk of contamination of the multidose vial during withdrawal of each dose is the 
responsibility of the user. 
 



55 

Record date and time of the first dose withdrawal on the vial label. 
 
Between uses, return the multidose vial to the recommended storage conditions between 2° and 8° C. 
The multidose vial should preferably be used within 24 hours after first withdrawal. 
 
Data are available that suggest that multidose vials could be used up to a maximum of 72 hours after 
first withdrawal, although such pro-longed storage periods should not be the preferred option. 
 
Any unused vaccine or waste material should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Seqirus S.r.l. 
Via del Pozzo 3/A, S. Martino 
53035 Monteriggioni (SI) 
Italy 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/577/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19 October 2009 
Date of latest renewal: 19 October 2014 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/. 
 

  

http://www.ema.europa.eu/


56 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE 
AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE 
AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
E. SPECIFIC OBLIGATIONS TO COMPLETE POST AUTHORISATION 

MEASURES FOR THE MARKETING AUTHORISATION UNDER 
EXCEPTIONAL CIRCUMSTANCES 

 
 



57 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturers of the biological active substance 
 
Seqirus Vaccines Ltd 
Gaskill Road, Speke, Liverpool 
L24 9GR 
UK 
 
Name and address of the manufacturer responsible for batch release 
 
Seqirus Vaccines Ltd 
Gaskill Road, Speke, Liverpool 
L24 9GR 
UK 
 
Seqirus Netherlands B.V. 
Paasheuvelweg 28 
1105BJ Amsterdam 
Netherlands 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
Foclivia 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 Foclivia takes due account 
of the officially declared pandemic strain. 
 
• Official batch release 
 
In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be undertaken 
by a state laboratory or a laboratory designated for that purpose. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING  

AUTHORISATION 
 
• Periodic Safety Update Reports 
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
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 pandemic preparedness 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 



58 

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. 

 
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 narrow SMQ “Guillain-Barré syndrome” 

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. 



59 

 
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. 
- All tables will be based on generic and not product-specific data1. Product-specific data can 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 
 
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. 

 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND  

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 

 
1 Based on the assumption that product name will not be provided in a significant proportion of cases. 



60 

E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 
FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL 
CIRCUMSTANCES 

 
This being an approval under exceptional circumstances and pursuant to Article 14(8) of Regulation 
(EC) No 726/2004, the MAH shall conduct, within the stated timeframe, the following measures: 
 

Description Due date 
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. 

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. 

 
  



61 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



62 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



63 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARDBOARD BOX FOR SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Foclivia suspension for injection in pre-filled syringe 
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose (0.5 ml) contains: Active Ingredients: Influenza virus surface antigens (haemagglutinin and 
neuraminidase), propagated in fertilised hen’s eggs from healthy chicken flocks, and adjuvanted with 
MF59C.1, of strain: 
 
A/Vietnam/1194/2004 (H5N1) 7.5 micrograms haemagglutinin 
 
Adjuvant: MF59C.1 oil in water emulsion containing squalene, as the oil phase, stabilised with 
polysorbate 80 and sorbitan trioleate in a citrate buffer (sodium citrate, citric acid). 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride, potassium chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate, 
magnesium chloride hexahydrate, calcium chloride dihydrate, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection. 
 
1 x single dose (0.5 ml) pre-filled syringe with needle 
1 x single dose (0.5 ml) pre-filled syringe without needle 
10 x single dose (0.5 ml) pre-filled syringes with needle 
10 x single dose (0.5 ml) pre-filled syringe without needle 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
To be administered intramuscularly into the deltoid muscle. 
 
Warning: Do not inject intravascularly or intradermally. 
 
Read the package leaflet before use. 
 
Gently shake before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 



64 

 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP.: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a 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 regulations. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Seqirus S.r.l.  
Via del Pozzo 3/A, S. Martino 
53035 Monteriggioni (SI) 
Italy. 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/577/001 1 prefilled syringe with needle 
EU/1/09/577/002 10 prefilled syringes with needle 
EU/1/09/577/005 1 prefilled syringe without needle 
EU/1/09/577/006 10 prefilled syringes without needle 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 



65 

17. UNIQUE  IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



66 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARDBOARD BOX FOR 1-DOSE VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Foclivia suspension for injection 
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose (0.5 ml) contains: Active Ingredients: Influenza virus surface antigens (haemagglutinin and 
neuraminidase), propagated in fertilised hen’s eggs from healthy chicken flocks, and adjuvanted with 
MF59C.1, of strain: 
 
A/Vietnam/1194/2004 (H5N1) 7.5 micrograms haemagglutinin 
 
Adjuvant: MF59C.1 oil in water emulsion containing squalene, as the oil phase, stabilised with 
polysorbate 80 and sorbitan trioleate in a citrate buffer (sodium citrate, citric acid). 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride, potassium chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate, 
magnesium chloride hexahydrate, calcium chloride dihydrate, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection. 
 
Vial 
10 x 1 dose 
1 dose (0.5 ml) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
To be administered intramuscularly into the deltoid muscle. 
 
Warning: Do not inject intravascularly or intradermally. 
 
Read the package leaflet before use. 
 
Gently shake before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 



67 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP.: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a 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. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Seqirus S.r.l.   
Via del Pozzo 3/A, S. Martino 
53035 Monteriggioni (SI) 
Italy. 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/577/003 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE  IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 



68 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



69 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARDBOARD BOX FOR 10-DOSE VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Foclivia suspension for injection in multidose container 
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose (0.5 ml) contains: Active Ingredients: Influenza virus surface antigens (haemagglutinin and 
neuraminidase), propagated in fertilised hen’s eggs from healthy chicken flocks, and adjuvanted with 
MF59C.1, of strain: 
 
A/Vietnam/1194/2004 (H5N1) 7.5 micrograms haemagglutinin 
 
Adjuvant: MF59C.1 oil in water emulsion containing squalene, as the oil phase, stabilised with 
polysorbate 80 and sorbitan trioleate in a citrate buffer (sodium citrate, citric acid). 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride, potassium chloride, potassium dihydrogen phosphate, disodium phosphate dihydrate, 
magnesium chloride hexahydrate, calcium chloride dihydrate, thiomersal, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection. 
 
Vial 
10 x 10 doses 
1 dose (0.5 ml) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
To be administered intramuscularly into the deltoid muscle. 
 
Warning: Do not inject intravascularly or intradermally. 
 
Read the package leaflet before use. 
 
Gently shake before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 



70 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP.: 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a 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 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Seqirus S.r.l.   
Via del Pozzo 3/A, S. Martino 
53035 Monteriggioni (SI) 
Italy. 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/09/577/004 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE  IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 



71 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



72 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL FOR SYRINGE AND 1-DOSE VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Foclivia injection 
Pandemic influenza vaccine (surface antigen, inactivated, adjuvanted) 
I.M. injection into the deltoid muscle 
 
 
2. METHOD OF ADMINISTRATION 
 
Gently shake before use. 
 
 
3. EXPIRY DATE 
 
EXP.: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 dose (0.5 ml) 
 
 
6. OTHER 
 
Seqirus S.r.l. - Italy 
Store in a refrigerator. 
 



73 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL FOR 10-DOSE VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Foclivia injection 
Pandemic Influenza Vaccine (surface antigen, inactivated, adjuvanted) 
I.M. injection into the deltoid muscle 
 
 
2. METHOD OF ADMINISTRATION 
 
Gently shake before use. 
 
 
3. EXPIRY DATE 
 
EXP.: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml vial containing 10 doses (0.5 ml/dose) 
 
 
6. OTHER 
 
Seqirus S.r.l. - Italy 
Store in a refrigerator. 
 

  



74 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



75 

Package leaflet: Information for the user 
 

Foclivia suspension for injection in pre-filled syringe 
Pandemic Influenza Vaccine (H5N1) (surface antigen, inactivated, adjuvanted) 

 
Read all of this leaflet carefully before you receive this vaccine because it contains important 
information for you. 
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or nurse. 
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What Foclivia is and what it is used for 
2. What you need to know before you receive Foclivia 
3. How Foclivia is given 
4. Possible side effects 
5. How to store Foclivia 
6. Contents of the pack and other information 
 
 
1. What Foclivia is and what it is used for 
 
Foclivia is a vaccine intended to be given to prevent influenza (flu) in an officially declared pandemic. 
 
Pandemic flu is a type of influenza that happens at intervals that vary from less than 10 years to many 
decades. It spreads rapidly around the world. The signs of pandemic flu are similar to those of 
ordinary flu but may be more serious. 
 
It is for use in adults (from 18 to 60 years old) and elderly (over 60 years) to prevent flu caused by the 
H5N1 type of the virus. 
 
When a person is given the vaccine, the body’s natural defence system (immune system) produces its 
own protection (antibodies) against the disease. None of the ingredients in the vaccine can cause flu. 
 
As with all vaccines, Foclivia may not fully protect all persons who are vaccinated. 
 
 
2. What you need to know before you receive Foclivia 
 
Foclivia should not be given if you: 
- have experienced serious allergic reaction (i.e. life-threatening) to any of the constituents of Foclivia, 
- are allergic (hypersensitive) to influenza vaccines or any of the ingredients of Foclivia, 
- are allergic to eggs, chicken protein, ovalbumin, 
- are allergic to kanamycin sulphate and neomycin sulphate (antibiotics), formaldehyde, 

cetyltrimethylammonium bromide (CTAB). 
- 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, you may still be given the vaccine. This is as long as 

medical treatment is available straight away, in case you have an allergic reaction. 
 



76 

Warnings and precautions 
 
Talk to your doctor or nurse before having this vaccine: 
 
- if you feel feverish, 
- if you have any illness or infection, 
- if you are having immunosuppressive therapy, e.g. corticosteroid treatment or chemotherapy for 

cancer, or if you have any condition which makes you prone to infections (immunodeficiency 
conditions). 

 
Please inform your doctor or nurse if you have a bleeding problem or bruise easily. 
 
The doctor should inform you about the posibility to experience convulsion, in particular if you have 
had previous history of epilepsy. 
 
Fainting can occur following, or even before, any needle injection. Therefore, tell the doctor or nurse 
if you fainted with a previous injection. 
 
Foclivia may not fully protect everyone who is vaccinated, especially elderly subjects and those with 
weakened immune systems, such as HIV patients, or those with underlying long term medical 
problems, such as diabetes, lung disease or heart problems. Tell your doctor if you have a weak 
immune system or an underlying long term medical problem. 
 
In any of these cases, TELL YOUR DOCTOR OR NURSE, as vaccination may not be recommended, 
or may need to be delayed. 
 
Other medicines and Foclivia 
Tell your doctor or nurse if you are taking or have recently taken or might take any other medicines, 
including medicines obtained without a prescription or have recently received any other vaccine. 
Foclivia can be given at the same time as non-adjuvanted seasonal influenza vaccines. There is no 
information on administration of Foclivia with non-influenza vaccines. If administration of Foclivia 
with other vaccines cannot be avoided, the vaccines should be injected into separate limbs. In such 
cases, you should be aware that the side effects may be more intense. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or nurse for advice before taking this vaccine. Your doctor needs to assess the benefits and 
potential risks of giving you the vaccine.  
 
Driving and using machines 
Some side effects listed in Section 4. “Possible side effects” may affect your ability to drive or use 
tools or machines.  
 
Foclivia contains sodium and potassium 
Foclivia contains less than 1 mmol sodium (23 mg) and less than 1 mmol of potassium (39 mg) per 
dose. It is essentially sodium- and potassium-free. 
 
 
3. How Foclivia is given 
 
Your doctor or nurse administers the vaccine in accordance with official recommendations. 
A dose (0.5 ml) of the vaccine will be injected into the upper arm (deltoid muscle) or upper thigh, 
depending on the muscle mass. 
 
A second dose of vaccine should be given after an interval of at least 3 weeks. 
 
 



77 

4. Possible side effects 
 
Like all medicines, Foclivia can cause side effects, although not everybody gets them. 
 
Allergic reactions may occur following vaccination, in rare cases leading to shock. Doctors are aware 
of this possibility and have emergency treatment available for use in such cases. 
 
The side effects listed below have occurred with Foclivia in clinical studies in adults, including 
the elderly: 
 
Very common (affects more than 1 user in 10): 
• Pain at the site of injection 
• Hardening of the skin at the injection site 
• Injection site redness  
• Injection site swelling 
• Aching muscles 
• Headache 
• Fatigue 
• Generally feeling unwell 
• Shivering 
 
Common (affects 1 to 10 users in 100): 
• Brusing of the skin at the injection site 
• Aching joints 
• Fever and nausea 
• Sweating 
 
Rare (affects 1 to 10 users in 10,000): 
• Anaphylaxis (severe allergic reactions) 
 
These side effects usually disappear within 1-2 days without treatment. If they persist, CONSULT 
YOUR DOCTOR. 
 
Undesirable effects in patients with underlying long term medical problems such as diabetes, lung 
disease or heart problems and weakened immune systems (immunocompromised) such as HIV 
patients 
Nausea, aching joints, diarrhoea and loss of appetite were reported very commonly in this population. 
In addition, vomiting was commonly reported.   
 
Side effects from clinical study in children (6 months to 17 years of age) 
General side effects reported very commonly in the 6 months to 35 months of age group were 
injection site redness, muscle ache, irritability and unusual crying. Very commonly reported reactions 
in the 36 months to 17 years of age group were pain, headache and fatigue. 
 
Other rare side effects observed after routine use 
The side effects listed below have occurred in the days or weeks after vaccination with another 
vaccine called Focetria H1N1v similar to Foclivia. These side effects may occur with Foclivia.  
  
• Generalised skin reactions including  

• Itching 
• Urticaria (hives) 
• Rash or swelling of the skin and mucous membranes 

 
• Disorders of the gut such as  

• Nausea 
• Vomiting 



78 

• Abdominal pain  
• Diarrhoea 

 
• Headache, dizziness, drowsiness, fainting. 

 
• Neurological disorders such as  

• Severe stabbing or throbbing pain along one or more nerves 
• Tingling 
• Fits 
• Neuritis (inflammation of nerves) 

 
• Swollen lymph nodes, palpitations (irregular or forceful heart beat), tachycardia (faster than 

normal heart beat), weakness, pain in the extremities, cough and asthenia (unusual weakness). 
 
• Allergic reactions possibly with shortness of breath, wheezing, swelling of the throat, or leading 

to a dangerous decrease of blood pressure, which, if untreated, may lead to shock. Doctors are 
aware of this possibility and have emergency treatment available for use in such cases. 

 
• Angioedema (abnormal swelling of the skin, usually around the eyes, lips, tongue, hands or feet, 

due to an allergic reaction). 
 
Data in children and adolescents suggest a slight decrease in side effects after the second dose of the 
vaccine, with no increase in rates of fever. 
 
In addition, the side effects listed below have occurred in the days or weeks after vaccination with 
vaccines given routinely every year to prevent seasonal flu. These side effects may occur with 
Foclivia. 
 
• Low blood platelet count which can result in bleeding or bruising. 
• Vasculitis (inflammation of the blood vessels which can cause skin rashes, joint pain and kidney 

problems). 
• Erythema multiforme (type of allergic skin reaction that occurs in response to medications, 

infections, or illness). 
• Neurological disorders such as encephalomyelitis (inflammation of the central nervous system), 

and a type of paralysis known as Guillain-Barré Syndrome. 
• Swelling, pain and redness at the injection site extending to more than 10 cm and lasting more 

than one week (Injection site cellulitis-like reaction). 
• Extensive swelling of injected limb lasting more than one week. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed 
in Appendix V. By reporting side effects, you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Foclivia 
 
Keep this vaccine out of the sight and reach of children. 
 
Do not use Foclivia after the expiry date which is stated on the carton and the label after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. Discard if the vaccine has been frozen. Store in the 
original package in order to protect from light. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


79 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Foclivia contains 
 
- Active substance: 
The active ingredients of the vaccine are purified viral proteins (called haemagglutinin and 
neuraminidase). They are isolated from the surface of influenza virus particles, which are grown in 
fertilised hen’s eggs from healthy chicken flocks and inactivated with formaldehyde. These viral 
proteins are prepared from the strain of influenza virus that complies with the World Health 
Organisation recommendations and EU decision in an officially declared Pandemic situation. 
 
One dose (0.5 ml) of the vaccine contains at least 7.5 micrograms of haemagglutinin from the 
following recommended influenza virus strain: 
 
A/Vietnam/1194/2004 (H5N1) 
 
- Adjuvant: 
The vaccine contains an ‘adjuvant’ (a compound containing squalene) to stimulate a better response. 
The adjuvant includes also polysorbate 80 and sorbitan trioleate in a citrate buffer (sodium citrate, 
citric acid). 
 
- Other ingredients: 
The other ingredients are: sodium chloride, potassium chloride, potassium dihydrogen phosphate, 
disodium phosphate dihydrate, magnesium chloride hexahydrate, calcium chloride dihydrate and water 
for injections. 
 
What Foclivia looks like and contents of the pack 
Foclivia is a milky-white liquid. 
It is provided in a ready-to-use syringe, containing a single dose (0.5 ml) for injection, in box of 1 or 
10, with or without needle.  
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Seqirus S.r.l. 
Via del Pozzo 3/A, S. Martino 
53035 Monteriggioni (SI) 
Italy 
 
Manufacturer 
Seqirus Vaccines Ltd 
Gaskill Road, Speke, Liverpool 
L24 9GR 
UK  
 
Seqirus Netherlands B.V. 
Paasheuvelweg 28 
1105BJ Amsterdam 
Netherlands 
 



80 

This leaflet was last revised in {MM/YYYY}. 
 
Foclivia 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 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 web site: 
http://www.ema.europa.eu. 
 
----------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Instructions for administration of the vaccine: 
 
The vaccine should under no circumstances be administered intravascularly or intradermally. There 
are no data with Foclivia using the subcutaneous route of administration. 
 
When using a pre-filled syringe without a needle supplied with a Luer Lock system, remove the tip 
cap by unscrewing it in a counter-clockwise direction. Once the tip cap is removed, attach a needle to 
the syringe by screwing it on in a clockwise direction until it locks. Once the needle is locked in place, 
remove the needle protector and administer the vaccine. 
 
Ready-to-use syringe, containing a single dose of 0.5 ml for injection. 
 
Gently shake before use. After shaking, the normal appearance of Foclivia is a milky-white 
suspension. 
 
Any unused vaccine or waste material should be disposed of in accordance with local requirements. 
 

http://www.ema.europa.eu/


81 

Package leaflet: Information for the user 
 

Foclivia suspension for injection 
Pandemic Influenza Vaccine (H5N1) (surface antigen, inactivated, adjuvanted) 

 
Read all of this leaflet carefully before you receive this vaccine because it contains important 
information for you. 
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or nurse. 
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What Foclivia is and what it is used for 
2. What you need to know before you receive Foclivia 
3. How Foclivia is given 
4. Possible side effects 
5. How to store Foclivia 
6. Contents of the pack and other information 
 
 
1. What Foclivia is and what it is used for 
 
Foclivia is a vaccine intended to be given to prevent influenza (flu) in an officially declared pandemic. 
 
Pandemic flu is a type of influenza that happens at intervals that vary from less than 10 years to many 
decades. It spreads rapidly around the world. The signs of pandemic flu are similar to those of 
ordinary flu but may be more serious. 
 
It is for use in adults (from 18 to 60 years old) and elderly (over 60 years) to prevent flu caused by the 
H5N1 type of the virus. 
 
When a person is given the vaccine, the body’s natural defence system (immune system) produces its 
own protection (antibodies) against the disease. None of the ingredients in the vaccine can cause flu. 
 
As with all vaccines, Foclivia may not fully protect all persons who are vaccinated. 
 
 
2. What you need to know before you receive Foclivia 
 
Foclivia should not be given if you: 
- have experienced serious allergic reaction (i.e. life-threatening) to any of the constituents of 

Foclivia, 
- are allergic (hypersensitive) to influenza vaccines or any of the ingredients of Foclivia, 
- are allergic to eggs, chicken protein, ovalbumin, 
- are allergic to kanamycin sulphate and neomycin sulphate (antibiotics), formaldehyde, 

cetyltrimethylammonium bromide (CTAB). 
- 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, you may still be given the vaccine. This is as long as 

medical treatment is available straight away, in case you have an allergic reaction. 
 



82 

Warnings and precautions 
 
Talk to your doctor or nurse before having this vaccine: 
 
- if you feel feverish, 
- if you have any illness or infection, 
- if you are having immunosuppressive therapy, e.g. corticosteroid treatment or chemotherapy for 

cancer, or if you have any condition which makes you prone to infections (immunodeficiency 
conditions). 

 
Please inform your doctor or nurse if you have a bleeding problem or bruise easily. 
 
The doctor should inform you about the posibility to experience convulsion, in particular if you have 
had previous history of epilepsy. 
 
Fainting can occur following, or even before, any needle injection. Therefore, tell the doctor or nurse 
if you fainted with a previous injection. 
 
Foclivia may not fully protect everyone who is vaccinated, especially elderly subjects and those with 
weakened immune systems, such as HIV patients, or those with underlying long term medical 
problems, such as diabetes, lung disease or heart problems. Tell your doctor if you have a weak 
immune system or an underlying long term medical problem. 
 
In any of these cases, TELL YOUR DOCTOR OR NURSE, as vaccination may not be recommended, 
or may need to be delayed. 
 
Other medicines and Foclivia 
Tell your doctor or nurse if you are taking or have recently taken or might take any other medicines, 
including medicines obtained without a prescription or have recently received any other vaccine. 
Foclivia can be given at the same time as non-adjuvanted seasonal influenza vaccines. There is no 
information on administration of Foclivia with non-influenza vaccines. If administration of Foclivia 
with other vaccines cannot be avoided, the vaccines should be injected into separate limbs. In such 
cases, you should be aware that the side effects may be more intense. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or nurse for advice before taking this vaccine. Your doctor needs to assess the benefits and 
potential risks of giving you the vaccine.  
 
Driving and using machines 
Some side effects listed in Section 4. “Possible side effects” may affect your ability to drive or use 
tools or machines.  
 
Foclivia contains sodium and potassium 
Foclivia contains less than 1 mmol sodium (23 mg) and less than 1 mmol of potassium (39 mg) per 
dose. It is essentially sodium- and potassium-free. 
 
 
3. How Foclivia is given 
 
Your doctor or nurse administers the vaccine in accordance with official recommendations. 
A dose (0.5 ml) of the vaccine will be injected into the upper arm (deltoid muscle) or upper thigh, 
depending on the muscle mass. 
 
A second dose of vaccine should be given after an interval of at least 3 weeks. 
 
 



83 

4. Possible side effects 
 
Like all medicines, Foclivia can cause side effects, although not everybody gets them. 
 
Allergic reactions may occur following vaccination, in rare cases leading to shock. Doctors are aware 
of this possibility and have emergency treatment available for use in such cases. 
 
The side effects listed below have occurred with Foclivia in clinical studies in adults, including 
the elderly: 
 
Very common (affects more than 1 user in 10): 
• Pain at the site of injection 
• Hardening of the skin at the injection site 
• Injection site redness  
• Injection site swelling 
• Aching muscles 
• Headache 
• Fatigue 
• Generally feeling unwell 
• Shivering 
 
Common (affects 1 to 10 users in 100): 
• Brusing of the skin at the injection site 
• Aching joints 
• Fever and nausea 
• Sweating 
 
Rare (affects 1 to 10 users in 10,000):  
• Anaphylaxis (severe allergic reactions) 
 
These side effects usually disappear within 1-2 days without treatment. If they persist, CONSULT 
YOUR DOCTOR. 
 
Undesirable effects in patients with underlying long term medical problems such as diabetes, lung 
disease or heart problems and weakened immune systems (immunocompromised) such as HIV 
patients 
Nausea, aching joints, diarrhoea and loss of appetite were reported very commonly in this population. 
In addition, vomiting was commonly reported.   
 
Side effects from clinical study in children (6 months to 17 years of age) 
General side effects reported very commonly in the 6 months to 35 months of age group were 
injection site redness, muscle ache, irritability and unusual crying. Very commonly reported reactions 
in the 36 months to 17 years of age group were pain, headache and fatigue. 
 
Other rare side effects observed after routine use 
The side effects listed below have occurred in the days or weeks after vaccination with another 
vaccine called Focetria H1N1v similar to Foclivia. These side effects may occur with Foclivia.  
 
• Generalised skin reactions including  

• Itching 
• Urticaria (hives) 
• Rash or swelling of the skin and mucous membranes 

 
• Disorders of the gut such as  

• Nausea 
• Vomiting 



84 

• Abdominal pain  
• Diarrhoea 

 
• Headache, dizziness, drowsiness, fainting. 
 
• Neurological disorders such as  

• Severe stabbing or throbbing pain along one or more nerves 
• Tingling 
• Fits 
• Neuritis (inflammation of nerves) 

 
• Swollen lymph nodes, palpitations (irregular or forceful heart beat), tachycardia (faster than 

normal heart beat), weakness, pain in the extremities, cough and asthenia (unusual weakness). 
 
• Allergic reactions possibly with shortness of breath, wheezing, swelling of the throat, or leading 

to a dangerous decrease of blood pressure, which, if untreated, may lead to shock. Doctors are 
aware of this possibility and have emergency treatment available for use in such cases. 

 
• Angioedema (abnormal swelling of the skin, usually around the eyes, lips, tongue, hands or feet, 

due to an allergic reaction). 
 
Data in children and adolescents suggest a slight decrease in side effects after the second dose of the 
vaccine, with no increase in rates of fever. 
 
In addition, the side effects listed below have occurred in the days or weeks after vaccination with 
vaccines given routinely every year to prevent seasonal flu. These side effects may occur with 
Foclivia. 
 
• Low blood platelet count which can result in bleeding or bruising. 
• Vasculitis (inflammation of the blood vessels which can cause skin rashes, joint pain and kidney 

problems). 
• Erythema multiforme (type of allergic skin reaction that occurs in response to medications, 

infections, or illness). 
• Neurological disorders such as encephalomyelitis (inflammation of the central nervous system), 

and a type of paralysis known as Guillain-Barré Syndrome. 
• Swelling, pain and redness at the injection site extending to more than 10 cm and lasting more 

than one week (Injection site cellulitis-like reaction). 
• Extensive swelling of injected limb lasting more than one week. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed 
in Appendix V. By reporting side effects, you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Foclivia 
 
Keep this vaccine out of the sight and reach of children. 
 
Do not use Foclivia after the expiry date which is stated on the carton and the label after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. Discard if the vaccine has been frozen.  Store in the 
original package in order to protect from light. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


85 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Foclivia contains 
 
- Active substance: 
The active ingredients of the vaccine are purified viral proteins (called haemagglutinin and 
neuraminidase). They are isolated from the surface of influenza virus particles, which are grown in 
fertilised hen’s eggs from healthy chicken flocks and inactivated with formaldehyde. These viral 
proteins are prepared from the strain of influenza virus that complies with the World Health 
Organisation recommendations and EU decision in an officially declared Pandemic situation. 
 
One dose (0.5 ml) of the vaccine contains at least 7.5 micrograms of haemagglutinin from the 
following recommended influenza virus strain: 
 
A/Vietnam/1194/2004 (H5N1) 
 
- Adjuvant: 
The vaccine contains an ‘adjuvant’ (a compound containing squalene) to stimulate a better response. 
The adjuvant includes also polysorbate 80 and sorbitan trioleate in a citrate buffer (sodium citrate, 
citric acid). 
 
- Other ingredients: 
The other ingredients are: sodium chloride, potassium chloride, potassium dihydrogen phosphate, 
disodium phosphate dihydrate, magnesium chloride hexahydrate, calcium chloride dihydrate and water 
for injections. 
 
What Foclivia looks like and contents of the pack 
Foclivia is a milky-white liquid. 
It is provided in a vial containing a single dose (0.5 ml) for injection. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Seqirus S.r.l. 
Via del Pozzo 3/A, S. Martino 
53035 Monteriggioni (SI) 
Italy 
 
Manufacturer 
Seqirus Vaccines Ltd 
Gaskill Road, Speke, Liverpool 
L24 9GR 
UK  
 
Seqirus Netherlands B.V. 
Paasheuvelweg 28 
1105BJ Amsterdam 
Netherlands 
 
 
This leaflet was last revised in {MM/YYYY}. 
 
Foclivia has been authorised under “Exceptional Circumstances”. 
This means that for scientific reasons, it has not been possible to obtain complete information on this 



86 

medicinal product. The European Medicines Agency (EMA) 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 web site: 
http://www.ema.europa.eu. 
 
----------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Single dose vial: 1 vial containing a single dose (0.5 ml) for injection 
 
Instructions for administration of the vaccine: 
 
The vaccine should under no circumstances be administered intravascularly or intradermally. There 
are no data with Foclivia using the subcutaneous route of administration. 
 
Gently shake before use. After shaking, the normal appearance of Foclivia is a milky-white 
suspension. 
 
Any unused vaccine or waste material should be disposed of in accordance with local requirements. 
 

http://www.ema.europa.eu/


87 

Package leaflet: Information for the user 
 

Foclivia suspension for injection in multidose container 
Pandemic Influenza Vaccine (H5N1) (surface antigen, inactivated, adjuvanted) 

 
Read all of this leaflet carefully before you receive this vaccine because it contains important 
information for you. 
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or nurse. 
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What Foclivia is and what it is used for 
2. What you need to know before you receive Foclivia 
3. How Foclivia is given 
4. Possible side effects 
5. How to store Foclivia 
6. Contents of the pack and other information 
 
 
1. What Foclivia is and what it is used for 
 
Foclivia is a vaccine intended to be given to prevent influenza (flu) in an officially declared pandemic. 
 
Pandemic flu is a type of influenza that happens at intervals that vary from less than 10 years to many 
decades. It spreads rapidly around the world. The signs of pandemic flu are similar to those of 
ordinary flu but may be more serious. 
 
It is for use in adults (from 18 to 60 years old) and elderly (over 60 years) to prevent flu caused by the 
H5N1 type of the virus. 
 
When a person is given the vaccine, the body’s natural defence system (immune system) produces its 
own protection (antibodies) against the disease. None of the ingredients in the vaccine can cause flu. 
 
As with all vaccines, Foclivia may not fully protect all persons who are vaccinated. 
 
 
2. What you need to know before you receive Foclivia 
 
Foclivia should not be given if you: 
- have experienced serious allergic reaction (i.e. life-threatening) to any of the constituents of 

Foclivia, 
- are allergic (hypersensitive) to influenza vaccines or any of the ingredients of Foclivia, 
- are allergic to eggs, chicken protein, ovalbumin, 
- are allergic to kanamycin sulphate and neomycin sulphate (antibiotics), formaldehyde, 

cetyltrimethylammonium bromide (CTAB). 
- 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, you may still be given the vaccine. This is as long as 

medical treatment is available straight away, in case you have an allergic reaction. 
 



88 

Warnings and precautions 
 
Talk to your doctor or nurse before having this vaccine: 
 
- if you feel feverish, 
- if you have any illness or infection, 
- if you are having immunosuppressive therapy, e.g. corticosteroid treatment or chemotherapy for 

cancer, or if you have any condition which makes you prone to infections (immunodeficiency 
conditions). 

 
Please inform your doctor or nurse if you have a bleeding problem or bruise easily. 
 
The doctor should inform you about the posibility to experience convulsion, in particular if you have 
had previous history of epilepsy. 
 
Fainting can occur following, or even before, any needle injection. Therefore, tell the doctor or nurse 
if you fainted with a previous injection. 
 
Foclivia may not fully protect everyone who is vaccinated, especially elderly subjects and those with 
weakened immune systems, such as HIV patients, or those with underlying long term medical 
problems, such as diabetes, lung disease or heart problems. Tell your doctor if you have a weak 
immune system or an underlying long term medical problem. 
 
In any of these cases, TELL YOUR DOCTOR OR NURSE, as vaccination may not be recommended, 
or may need to be delayed. 
 
Other medicines and Foclivia 
Tell your doctor or nurse if you are taking or have recently taken or might take any other medicines, 
including medicines obtained without a prescription or have recently received any other vaccine.  
 
Foclivia can be given at the same time as non-adjuvanted seasonal influenza vaccines. There is no 
information on administration of Foclivia with non-influenza vaccines. If administration of Foclivia 
with other vaccines cannot be avoided, the vaccines should be injected into separate limbs. In such 
cases, you should be aware that the side effects may be more intense. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or nurse for advice before taking this vaccine. Your doctor needs to assess the benefits and 
potential risks of giving you the vaccine.  
 
Driving and using machines 
Some side effects listed in Section 4. “Possible side effects” may affect your ability to drive or use 
tools or machines.  
 
Foclivia contains thiomersal 
Foclivia contains Thiomersal as a preservative and it is possible that you may experience an allergic 
reaction. Tell your doctor if you have any known allergies. 
 
Foclivia contains sodium and potassium 
Foclivia contains less than 1 mmol sodium (23 mg) and less than 1 mmol of potassium (39 mg) per 
dose. It is essentially sodium- and potassium-free. 
 
 
3. How Foclivia is given 
 
Your doctor or nurse administers the vaccine in accordance with official recommendations. 
A dose (0.5 ml) of the vaccine will be injected into the upper arm (deltoid muscle) or upper thigh, 



89 

depending on the muscle mass. 
 
A second dose of vaccine should be given after an interval of at least 3 weeks. 
 
 
4. Possible side effects 
 
Like all medicines, Foclivia can cause side effects, although not everybody gets them. 
 
Allergic reactions may occur following vaccination, in rare cases leading to shock. Doctors are aware 
of this possibility and have emergency treatment available for use in such cases. 
 
The side effects listed below have occurred with Foclivia in clinical studies in adults, including 
the elderly: 
 
Very common (affects more than 1 user in 10): 
• Pain at the site of injection 
• Hardening of the skin at the injection site 
• Injection site redness  
• Injection site swelling 
• Aching muscles 
• Headache 
• Fatigue 
• Generally feeling unwell 
• Shivering 
 
Common (affects 1 to 10 users in 100): 
• Brusing of the skin at the injection site 
• Aching joints 
• Fever and nausea 
• Sweating 
 
Rare (affects 1 to 10 users in 10,000): 
• Anaphylaxis (severe allergic reactions) 
 
These side effects usually disappear within 1-2 days without treatment. If they persist, CONSULT 
YOUR DOCTOR. 
 
Undesirable effects in patients with underlying long term medical problems such as diabetes, lung 
disease or heart problems and weakened immune systems (immunocompromised) such as HIV 
patients 
Nausea, aching joints, diarrhoea and loss of appetite were reported very commonly in this population. 
In addition, vomiting was commonly reported.   
 
Side effects from clinical study in children (6 months to 17 years of age) 
General side effects reported very commonly in the 6 months to 35 months of age group were 
injection site redness, muscle ache, irritability and unusual crying. Very commonly reported reactions 
in the 36 months to 17 years of age group were pain, headache and fatigue. 
 
Other rare side effects observed after routine use 
The side effects listed below have occurred in the days or weeks after vaccination with another 
vaccine called Focetria H1N1v similar to Foclivia. These side effects may occur with Foclivia.  
 
• Generalised skin reactions including  

• Itching 
• Urticaria (hives) 



90 

• Rash or swelling of the skin and mucous membranes 
 
• Disorders of the gut such as  

• Nausea 
• Vomiting 
• Abdominal pain  
• Diarrhoea 

 
• Headache, dizziness, drowsiness, fainting. 
 
• Neurological disorders such as  

• Severe stabbing or throbbing pain along one or more nerves 
• Tingling 
• Fits 
• Neuritis (inflammation of nerves) 

 
• Swollen lymph nodes, palpitations (irregular or forceful heart beat), tachycardia (faster than 

normal heart beat), weakness, pain in the extremities, cough and asthenia (unusual weakness). 
 

• Allergic reactions possibly with shortness of breath, wheezing, swelling of the throat, or leading 
to a dangerous decrease of blood pressure, which, if untreated, may lead to shock. Doctors are 
aware of this possibility and have emergency treatment available for use in such cases. 

 
• Angioedema (abnormal swelling of the skin, usually around the eyes, lips, tongue, hands or feet, 

due to an allergic reaction). 
 
Data in children and adolescents suggest a slight decrease in side effects after the second dose of the 
vaccine, with no increase in rates of fever. 
 
In addition, the side effects listed below have occurred in the days or weeks after vaccination with 
vaccines given routinely every year to prevent seasonal flu. These side effects may occur with 
Foclivia. 
 
• Low blood platelet count which can result in bleeding or bruising. 
• Vasculitis (inflammation of the blood vessels which can cause skin rashes, joint pain and kidney 

problems). 
• Erythema multiforme (type of allergic skin reaction that occurs in response to medications, 

infections, or illness). 
• Neurological disorders such as encephalomyelitis (inflammation of the central nervous system), 

and a type of paralysis known as Guillain-Barré Syndrome. 
• Swelling, pain and redness at the injection site extending to more than 10 cm and lasting more 

than one week (Injection site cellulitis-like reaction). 
• Extensive swelling of injected limb lasting more than one week. 
 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 
listed in this leaflet. You can also report side effects directly via the national reporting system listed 
in Appendix V. By reporting side effects, you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Foclivia 
 
Keep this vaccine out of the sight and reach of children. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


91 

Do not use Foclivia after the expiry date which is stated on the carton and the label after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. Discard if the vaccine has been frozen. Store in the 
original package in order to protect from light. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Foclivia contains 
 
- Active substance: 
The active ingredients of the vaccine are purified viral proteins (called haemagglutinin and 
neuraminidase). They are isolated from the surface of influenza virus particles, which are grown in 
fertilised hen’s eggs from healthy chicken flocks and inactivated with formaldehyde. These viral 
proteins are prepared from the strain of influenza virus that complies with the World Health 
Organisation recommendations and EU decision in an officially declared Pandemic situation. 
 
One dose (0.5 ml) of the vaccine contains at least 7.5 micrograms of haemagglutinin from the 
following recommended influenza virus strain: 
 
A/Vietnam/1194/2004 (H5N1) 
 
- Adjuvant: 
The vaccine contains an ‘adjuvant’ (a compound containing squalene) to stimulate a better response. 
The adjuvant includes also polysorbate 80 and sorbitan trioleate in a citrate buffer (sodium citrate, 
citric acid). 
 
- Other ingredients: 
The other ingredients are: thiomersal, sodium chloride, potassium chloride, potassium dihydrogen 
phosphate, disodium phosphate dihydrate, magnesium chloride hexahydrate, calcium chloride 
dihydrate and water for injections. 
 
What Foclivia looks like and contents of the pack 
Foclivia is a milky-white liquid. 
It is provided in a vial containing ten doses (0.5 ml each) for injection. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Seqirus S.r.l. 
Via del Pozzo 3/A, S. Martino 
53035 Monteriggioni (SI) 
Italy 
 
Manufacturer 
Seqirus Vaccines Ltd 
Gaskill Road, Speke, Liverpool 
L24 9GR 
UK  
 
Seqirus Netherlands B.V. 
Paasheuvelweg 28 
1105BJ Amsterdam 
Netherlands 



92 

 
 
This leaflet was last revised in {MM/YYYY}. 
 
Foclivia 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 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 web site: 
http://www.ema.europa.eu. 
 
_____________________________________________ 
 
The following information is intended for healthcare professionals only: 
 
Multidose vial: Vial containing 10 doses (0.5 ml each) for injection. 
 
Instructions for administration of the vaccine: 
 
The vaccine should under no circumstances be administered intravascularly or intradermally. There 
are no data with Foclivia using the subcutaneous route of administration. 
 
Gently shake the multidose vial each time before withdrawing a dose (0.5 ml) of the vaccine into a 
syringe. After shaking, the normal appearance of Foclivia is a milky-white suspension. 
Although Foclivia in multidose vials contains a preservative that inhibits microbial growth, 
minimisation of the risk of contamination of the multidose vial during withdrawal of each dose is the 
responsibility of the user. 
 
Record date and time of the first dose withdrawal on the vial label. 
 
Between uses, return the multidose vial to the recommended storage conditions between 2° and 8° C. 
The multidose vial should preferably be used within 24 hours after first withdrawal. 
 
Data are available that suggest that multidose vials could be used up to a maximum of 72 hours after 
first withdrawal, although such pro-longed storage periods should not be the preferred option. 
 
Any unused vaccine or waste material should be disposed of in accordance with local requirements. 
 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	E. SPECIFIC OBLIGATION TO COMPLETE POSTAUTHORISATION MEASURES FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES
	A. LABELLING
	B. PACKAGE LEAFLET