Aflunov

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
AFLUNOV suspension for injection in pre-filled syringe. 
Zoonotic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted). 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain: 
 
A/turkey/Turkey/1/2005 (H5N1)-like strain (NIBRG-23) (clade 2.2.1) 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 per 0.5 ml 
polysorbate 80 1.175 milligrams per 0.5 ml 
sorbitan trioleate 1.175 milligrams per 0.5 ml 
 
Excipient with known effect: 
The vaccine contains 1.899 milligrams of sodium and 0.081 milligrams of potassium per 0.5 ml dose.  
 
AFLUNOV may contain trace residues of egg and chicken proteins, ovalbumin, kanamycin, 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 
 
Active immunisation against H5N1 subtype of Influenza A virus. 
 
This indication is based on immunogenicity data from healthy subjects from the age of 18 years 
onwards following administration of two doses of the vaccine containing 
A/turkey/Turkey/1/2005 (H5N1)-like strain (see sections 4.4 and 5.1). 
 
AFLUNOV should be used in accordance with official recommendations. 
 
4.2 Posology and method of administration 
 
Posology 
Adults and elderly (18 years of age and above): 
One dose of 0.5 ml at an elected date. 
A second dose of 0.5 ml should be given after an interval of at least 3 weeks. 
 



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AFLUNOV has been evaluated in healthy adults (18-60 years of age) and healthy elderly 
(over 60 years of age) following a 1, 22 day primary vaccination schedule, and booster vaccination 
(see sections 4.8 and 5.1). 
 
There is limited experience in elderly over 70 years of age (see section 5.1). 
 
In the event of an officially declared influenza pandemic due to A/H5N1 virus, persons previously 
vaccinated with one or two doses of AFLUNOV that contained haemagglutinin (HA) antigen derived 
from a different clade of the same influenza subtype as the influenza pandemic strain may receive a 
single dose of AFLUNOV instead of two doses that are required in previously unvaccinated 
individuals (see section 5.1). 
 
Paediatric population 
The safety and efficacy of AFLUNOV 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. 
 
4.3 Contraindications 
 
History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues 
(egg and chicken proteins, ovalbumin, kanamycin and neomycin sulphate, formaldehyde and 
cetyltrimethylammonium bromide) of this vaccine. 
 
However, in a pandemic situation caused by the strain included in this vaccine, 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. 
 
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 (other 
than anaphylactic reaction) to the active substance, to any of the excipients listed in section 6.1 and to 
residues (eggs and chicken proteins, ovalbumin, kanamycin and 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. 
 
Immunization shall be postponed in patients with febrile illness or acute infection. 
 
The vaccine should under no circumstances be administered intravascularly or intradermally. 
 
There are no data with AFLUNOV using the subcutaneous route of administration. Therefore, 
healthcare providers need to assess the benefits and potential risks of administering the vaccine in 
individuals with thrombocytopenia or any bleeding disorder that would contraindicate intramuscular 
injection unless the potential benefit outweighs the risk of bleedings. 
 
Protection against influenza 
There is no immune correlate of protection established for influenza A (H5N1).  



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Based on humoral immune responses to the vaccine strain A/turkey/Turkey/1/2005 after two doses of 
AFLUNOV, a protective immune response may not be elicited in all vaccinees. 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 AFLUNOV with other H5N1 monovalent vaccines. 
 
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 
 
AFLUNOV 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 AFLUNOV 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. 
 
Following influenza vaccination, false positive serology test results may be obtained by the ELISA 
method for antibody to human immunodeficiency virus-1 (HIV-1), hepatitis C virus and, especially, 
human T-lymphotropic virus type 1 (HTLV-1). In such cases, the Western Blot method is negative. 
These transitory false positive results may be due to IgM production in response to the vaccine. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
Limited data were obtained from women who became pregnant during the course of clinical trials with 
AFLUNOV or similar pandemic H1N1v vaccines adjuvanted with MF59C.1. 
 
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 AFLUNOV) which 
contains the same amount of adjuvant MF59C.1 as AFLUNOV. 
 
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. 
 
Since AFLUNOV is expected not to be used in an emergency situation, its administration during 
pregnancy might be deferred as a precautionary approach. 
 
Healthcare providers need to assess the benefit and potential risks of administering the vaccine to 
pregnant women taking into consideration official recommendations. 



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Breast-feeding 
There are no data regarding the use of AFLUNOV during breast-feeding. The potential benefits 
to the mother and risks to the infant should be considered before administering AFLUNOV 
during breast-feeding. 
 
Fertility 
There are no data concerning human fertility. A study in rabbits did not indicate reproductive or 
developmental toxicity of AFLUNOV (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Some of the undesirable effects mentioned under section 4.8 may affect the ability to drive or operate 
machinery. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The incidence of adverse reactions has been evaluated in seven clinical trials in healthy subjects 
involving over 4300 adults and elderly receiving AFLUNOV (at least 7.5 µg HA, adjuvanted). 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 studies using AFLUNOV containing either the 
A/turkey/Turkey/1/2005 or the A/Vietnam/1194/2004 strain is comparable. 
 
Consistent with the data observed by trial for solicited reactions, there was a general trend towards 
decreased reports of local reactions after the second vaccination compared with the first injection. 
Irrespective of antigen dose, almost all systemic reactions were reported on the day of vaccination 
(day 1) or during the 3 days immediately following. 
 
Data on safety of a booster dose of AFLUNOV are limited to three trials (V87P1, V87P2 and 
V87P1E1) that included 116 adults (18-60 years) and 56 elderly subjects (>61 years). No increase in 
reactions was reported when a booster dose was administered 6 months-18 months later, after the 
initial dosing series. A slight increase in reactions in adults was reported when a booster dose was 
administered 18 months after the initial dosing series. In the elderly, the reported 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 doses (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). 



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MedDRA 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) 

Nervous system disorders Headache   Convulsions 

Gastrointestinal disorders  Nausea   

Skin and subcutaneous tissue 
disorders 

 Sweating Urticaria Eye swelling 

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 

Injection site 
ecchymosis, 
Fever, Malaise, 
Shivering 

Influenza like 
illness 

Anaphylaxis   

 
The majority of these side effects 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. 
 
 Study V87_25 Study V87_26 
 Medical conditions Healthy Immunocompromised 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 AFLUNOV 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 AFLUNOV 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).    
 
Post-marketing surveillance 
No post-marketing surveillance data are available following AFLUNOV administration. 
 



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Description of selected adverse reactions 
The following adverse events were reported from post-marketing surveillance with Focetria (an H1N1 
pandemic vaccine similar to AFLUNOV) which contains the same amount of adjuvant MF59C.1 as 
AFLUNOV, 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. 
 
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; angioedema. 
 
Muscoskeletal, 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 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). 
 
Paediatric population 
The incidence of AFLUNOV (A/Vietnam/1194/2004) adverse reactions has been evaluated in one 
clinical trial (V87P6) in children (6 months to 17 years old). Regardless of age, reactogencity was 
higher after the first dose than after the second vaccination. Reactogenicity after the third dose, 



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administered 12 months following the first dose, was higher than after both first and second doses. The 
percentages of subjects reporting local reactions were higher in the older age groups, mainly due to the 
higher reports for pain. In toddlers, erythema and tenderness were the most commonly reported 
solicited local reactions; irritability and unusual crying were the most commonly reported solicited 
systemic reactions. In children and adolescents, pain was the most frequently reported solicited local 
reaction, and fatigue and headache were the most commonly reported solicited systemic reactions. 
Across all ages, low percentages of subjects reported fever. 
 

 Injection 1 Injection 2 Injection 3 
 AFLUNOV AFLUNOV AFLUNOV 
Toddlers (6-<36 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-<9 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-<18 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% 

 
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 
 
Clinical trials with AFLUNOV have been conducted with either the former 
A/Vietnam/1194/2004 (H5N1) (clade 1) or the current A/turkey/Turkey/1/2005 (H5NI) vaccine strain 
(clade 2.2.1). 
 



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Immune response to AFLUNOV A/Vietnam/1194/2004 (H5N1) and A/turkey/Turkey/1/2005 (H5NI) 
 
Adults (18-60 years) 
A phase II clinical trial (V87P1) was conducted with AFLUNOV 
(A/Vietnam/1194/2004) in 312 healthy adults. Two doses of AFLUNOV were administered three 
weeks apart to 156 healthy adultsImmunogenicity was assessed in 149 subjects. In phase III clinical 
trial (V87P13) 2693 adult subjects were enrolled and 2566 received two doses of AFLUNOV 
(A/Vietnam/1194/2004) administered three weeks apart. Immunogenicity was assessed in a subset 
(n=197) of subjects . In a third clinical trial (V87P11) 194 adult subjects were enrolled and received 
two doses of AFLUNOV (A/turkey/Turkey/1/2005) 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 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 
 
MicroNeutralisation (MN) results against homologous A/Vietnam/1194/2004) 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 (A/Vietnam/1194/2004 and to A/ turkey/Turkey/1/2005) in subjects aged 61 years 



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and older (limited number of subjects were above 70 years of age; n=123) measured by SRH assay 
assessed in three 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 homologous A/Vietnam/1194/2004 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. 
 
Based on data obtained from trials V87P1, V87P11 and V87_13, persistence of antibodies after 
primary vaccination in elderly subjects as assessed by HI, SRH, and MN tests reduced 
from 1/2 to 1/5th of their post-vaccination level at day 202 as compared to day 43 after completion of 
primary schedules. Up to 50% (n=33) of the elderly subjects aged 62 to 88 years immunised with 
AFLUNOV in trial V87P1 were seroprotected at six months. 
 
A third (booster) dose of AFLUNOV was administered 6 months onwards after the primary 
vaccination. 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 
booster after 2nd dose 

Study V87P2 Adults 
booster after 2nd dose 

Study V87P1 Elderly 
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) 



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*  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 
 

Cross reactivity data in adults 
 

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

 
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 V87P12 
21 days after 2nd 

dose 
N=60 

Study V87P3 
21 days after 2nd dose 

N=30 

Study V87P13 
21 days after 2nd dose 

N=197 

SRH Seroprotection 
rate (95%CI)* 

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

Seroconversion 
rate (95%CI)** 

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

Seroconversion 
factor(95%CI)*** 

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

  N=60 N=30 N=197 
HI Seroprotection 

rate (95%CI)° 
28% (17-41) 24% (10-44) 23% (18-30) 

Seroconversion 
rate (95%CI)° 

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

Seroconversion 
factor (95%CI)°° 

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 
° measured by HI assay ≥ 40 
°° GMRs of HI 
 
MN results for the three clinical studies 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. 
 

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. 
 



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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. 
 
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 AFLUNOV (A/Vietnam/1194/2004) induced high and rapid serological 
response in subjects primed 6-8 years previously with two doses of a different surrogate H5N vaccine, 
having same formulation as AFLUNOV but using the strain H5N3. 
 
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 
AFLUNOV (A/Vietnam/1194/2004). 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 AFLUNOV 



13 

(A/Vietnam/1194/2004) dose, 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 rated 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 AFLUNOV (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 AFLUNOV 
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: 

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 

 

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) 



14 

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 AFLUNOV 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 population 
 
A clinical trial (V87P6) was conducted with AFLUNOV (A/Vietnam/1194/2004) in 471 children 
from 6 months to 17 years of age. Two doses of AFLUNOV 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-<36 months) 
Children 

(3-<9 years) 
Adolescents 

(9-<18 years) 
N=134 N=91 N=89 

HI 

% SP (95% CI) Day 43 97% (92-99) 
97% 

(91-99) 
89% 

(80-94) 

GMR Day 43 to Day 1 129 (109-151) 
117 

(97-142) 
67 

(51-88) 

% SC (95% CI)Day 43 97% (92-99) 
97% 

(91-99) 
89% 

(80-94) 

SRH 

 N=133 N=91 N=90 

% SP (95% CI) Day 43 100% (97-100) 
100% 

(96-100) 
100% 

(96-100) 

GMR (95% CI) Day 43 to Day 1 16  (14-18) 
15 

 (13-17) 
14 

 (12-16) 

% SC (95% CI) Day 43 98% (95-100) 
100% 

(96-100) 
99% 

(94-100) 
SP= seroprotection 
SC= seroconversion 
 
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). 



15 

 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
AFLUNOV in one or more subsets of the paediatric population in active immunisation against 
H5N1 subtype of Influenza A virus. See section 4.2 for information on paediatric use. 
 
Information from non-clinical studies 
Efficacy against challenge with virus homologous and heterologous to vaccine strains was evaluated 
in the ferret model. AFLUNOV(A/Vietnam/1194/2004) and an AFLUNOV-like H5N1 vaccine 
(A/turkey/Turkey/1/2005-like) were tested. Animals received one or two doses of vaccine 
containing 3.75 or 7.5 micrograms of antigen, followed by challenge with a lethal dose of 
A/Vietnam/1203/04 virus.  
 
All animals receiving 2 doses of AFLUNOV were protected, and 94% of animals receiving a single 
dose of AFLUNOV were protected. 87% of animals challenged with virus heterologous to the vaccine 
strain after 2 doses of vaccine were protected, and a single dose of heterologous vaccine 
protected 56% of the animals.  
 
In a similar study, intranasal challenge was delayed until approximately 4 months after the second 
dose of vaccine was administered. In this study 100% of animals were protected against homologous 
challenge, and 81% of animals were protected against heterologous challenge. Vaccination protected 
animals from lethal challenge even when HI antibody titres were low or undetectable. 
 
Efficacy against challenge with the heterologous virus A/Indonesia/5/2005 was also tested. Ferrets 
received one or two doses of vaccine (A/Vietnam/1194/2004). Two doses of vaccine protected 92% of 
animals, and a single dose of vaccine protected 50% of animals against challenge with the 
A/Indonesia/5/2005 virus. Lung damage was reduced in vaccinated groups. Viral shedding and viral 
titres in lungs were also reduced, suggesting that vaccination may reduce the risk of viral transmission. 
 
5.2 Pharmacokinetic properties 
 
Not applicable. 
 
5.3 Preclinical safety data 
 
Non-clinical data obtained with AFLUNOV 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 (E508), 
Potassium dihydrogen phosphate (E340), 
Disodium phosphate dihydrate (E339), 
Magnesium chloride hexahydrate (E511), 
Calcium chloride dihydrate (E509), 
Sodium citrate (E311), 
Citric acid (E330), 
Water for injections. 
 
For the adjuvant, see section 2 
 



16 

6.2 Incompatibilities 
 
In the absence of compatibility trials, this medicinal product must not be mixed with other 
medicinal products. 
 
6.3 Shelf life 
 
2 years. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Store in the original package in order to protect from light. 
 
6.5 Nature and contents of container 
 
0.5 ml in pre-filled syringe (type I glass) with plunger-stopper (bromo-butyl rubber). 
 
Packs of 1 or 10 pre-filled syringes. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
The vaccine should be allowed to reach room temperature before use. Gently shake before use. 
 
After shaking, the normal appearance of AFLUNOV 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 and 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/1/10/658/001-002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 29 November 2010 
Date of latest renewal: 17 July 2015 
 



17 

 
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/.  



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 
 



19 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER 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. 
 
• Official batch release 
 
In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be taken by 
a state laboratory or a laboratory designated for that purpose. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
Periodic Safety Update Reports (PSURs) 
 
PSUR submission when AFLUNOV is used during an influenza pandemic:  
During a pandemic situation, the frequency of submission of periodic safety update reports specified 
in Article 24 of Regulation 726/2004/EC will not be adequate for the safety monitoring of a pandemic 
vaccine for which high levels of exposure are expected within a short period of time. Such situation 
requires rapid notification of safety information that may have the greatest implications for 
risk-benefit balance in a pandemic. Prompt analysis of cumulative safety information, in light of extent 
of exposure, will be crucial for regulatory decisions and protection of the population to be vaccinated. 
In addition, duration a pandemic, resources needed for an in-depth evaluation of PSURs in the format 
as defined in Volume 9a of the Rules Governing Medicinal Product in the European Union may not be 
adequate for a rapid identification of a new safety issue. 
 
In consequence, as soon as the pandemic is declared and the zoonotic vaccine is used, the Marketing 
Authorisation Holder (MAH) shall submit more frequent simplified periodic safety update reports with 
a format and a periodicity defined in the “CHMP Recommendations for the Core Risk Management 
Plan for Influenza Vaccines prepared from viruses with the potential to cause a pandemic and intended 
for use outside of the core dossier context” (EMEA/49993/2008), and any subsequent update. 
 
 



20 

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. 

 
If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 

  



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



23 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARDBOARD BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
AFLUNOV suspension for injection in pre-filled syringe. 
Zoonotic influenza vaccine (H5N1) (surface antigen, inativated, adjuvanted) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One dose of 0.5 ml contains: Influenza virus surface antigens (haemagglutinin and neuraminidase), 
propagated in fertilised hens’ eggs from healthy chicken flocks, of strain: 
 
A/turkey/Turkey/1/2005 (H5N1)-like strain (NIBRG-23) (clade 2.2.1) 7.5 micrograms haemagglutinin 
 
Adjuvant: MF59C.1 oil in water emulsion containing squalene, as the oil phase, stabilised with 
polysorbate 80 and sorbitan trioleate. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride 
Potassium chloride (E508) 
Potassium dihydrogen phosphate (E340) 
Disodium phosphate dihydrate (E339) 
Magnesium chloride hexahydrate (E511) 
Calcium chloride dihydrate (E 509) 
Sodium citrate (E311) 
Citric acid (E330)Water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection. 
 
1 pre-filled syringe (0.5 ml) 
10 pre-filled syringes (0.5 ml) 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
To be administered intramuscularly into the deltoid muscle. 
Warning: Do not inject intravascularly or intradermally. 
 
Read the package leaflet before use. 
 
The vaccine should be allowed to reach room temperature before use. Gently shake before use. 
 
 



24 

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. 
 
 
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 
 
EU/1/10/658/001 1 prefilled syringe 
EU/1/10/658/002 10 prefilled syringes 
 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 



25 

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



26 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
LABEL FOR SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
AFLUNOV injection 
H5N1 Zoonotic influenza vaccine 
IM 
 
 
2. METHOD OF ADMINISTRATION 
 
  
 
 
3. EXPIRY DATE 
 
EXP.: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.5 ml 
 
 
6. OTHER 
 
Store in a refrigerator. 
Seqirus S.r.l. – Italy 
 

  



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



28 

Package leaflet: information for the user 
 

AFLUNOV suspension for injection in pre-filled syringe 
Zoonotic 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 AFLUNOV is and what it is used for 
2. What you need to know before you receive AFLUNOV 
3. How AFLUNOV is given 
4. Possible side effects 
5. How to store AFLUNOV 
6. Contents of the pack and other information 
 
 
1. What AFLUNOV is and what it is used for 
 
AFLUNOV is a vaccine for use in adults from 18 onwards, intended to be given in the context of 
outbreaks of zoonotic influenza viruses (coming from birds) with pandemic potential to prevent flu 
caused by H5N1 viruses similar to the vaccine strain reported in section 6.  
 
Zoonotic influenza viruses occasionally infect humans, and can cause disease ranging from mild upper 
respiratory infection (fever and cough) to rapid progression to severe pneumonia, acute respiratory 
distress syndrome, shock and even death. Human infections are primarily caused by contact with 
infected animals, but do not spread easily between people. 
 
AFLUNOV is intended also to be given when there is anticipation of a possible pandemic due to the 
same or a similar strain. 
 
When a person is given the vaccine, the immune system (the body’s natural defence system) will 
produce its own protection (antibodies) against the disease. None of the ingredients in the vaccine 
can cause flu. 
 
As with all vaccines, AFLUNOV may not fully protect all persons who are vaccinated. 
 
 
2. What you need to know before you receive AFLUNOV 
 
You should not receive AFLUNOV: 
 
• if you have previously had a sudden life-threatening allergic reaction to any ingredient of 

AFLUNOV (listed in section 6) or to any of the substances that may be present in trace amounts 
as follows: egg and chicken protein, ovalbumin, formaldehyde, kanamycin and neomycin 
sulphate (antibiotics) or 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, it may be appropriate for you to be vaccinated with 
AFLUNOV provided that appropriate medical treatment is immediately available in case of an 
allergic reaction. 

 



29 

Warnings and precautions 
 
Talk to your doctor or nurse before having this vaccine 
 
• if you have had any allergic reaction other than a sudden life-threatening allergic reaction to any 

ingredient contained in the vaccine, to egg and chicken protein, ovalbumin, formaldehyde, 
kanamycin and neomycin sulphate (antibiotics) or cetyltrimethylammonium bromide (CTAB) 
(see section 6. Further information); 

 
• if you have a severe infection with a high temperature (over 38°C). If this applies to you then 

your vaccination will usually be postponed until you are feeling better. A minor infection such 
as a cold should not be a problem, but your doctor or nurse should advise whether you could 
still be vaccinated with AFLUNOV; 

 
• if you are having a blood test to look for evidence of infection with certain viruses. In the first 

few weeks after vaccination with AFLUNOV the results of these tests may not be correct. Tell 
the doctor requesting these tests that you have recently been given AFLUNOV. 

 
• in the presence of immune deficiencies AFLUNOV may be administered but a protective 

immune response may not be elicited. 
 
Please inform your doctor or nurse if you have a bleeding problem or bruise easily. 
 
Fainting can occur following, or even before, any needle injection. Therefore tell the doctor or nurse if 
you fainted with a previous injection. 
 
AFLUNOV 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 AFLUNOV 
 
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. 
 
Data obtained in adults showed that AFLUNOV can be given at the same time as non-adjuvanted 
seasonal influenza vaccines. There is no information on administration of AFLUNOV with non-
influenza vaccines. If administration of AFLUNOV with other vaccines can not 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 receiving this vaccine. Your doctor needs to assess the benefits 
and potential risks of giving you the vaccine.   
 
Driving and using machines 
 
Some effects mentioned under section 4. “Possible side effects” may affect the ability to drive or use 
machines. 
 



30 

AFLUNOV contains sodium and potassium. 
 
AFLUNOV contains less than 1 mmol sodium (23 mg) and less than 1 mmol of potassium (39 mg) 
per 0.5 ml dose, i.e. essentially sodium- and potassium-free. 
 
 
3. How AFLUNOV is given 
 
Your doctor or nurse will administer the vaccine in accordance with official recommendations. 
The vaccine will be injected into the muscles of the upper arm (deltoid muscle). The vaccine should 
never be given into a vein. 
 
Adults from 18 onwards: 
One dose of 0.5 ml will be given. A second dose of 0.5 ml should be given after an interval of 
at least 3 weeks. 
 
There is limited experience in elderly over 70 years of age. 
 
Use in children 
 
Children from 6 months to 17 years of age 
There is limited experience in children between 6 months and 17 years of age. Vaccination is currently 
not recommended in this age group. 
 
Children aged less than 6 months of age  
Vaccination is currently not recommended in this age group. 
 
If you have any further questions on the use of this medicinal product, ask your doctor or nurse. 
 
  
4. Possible side effects 
 
Like all medicines, AFLUNOV 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 AFLUNOV 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. 
 
Common (affects 1 to 10 users in 100): 
• Brusing of the skin at the injection site 
• Aching joints 
• Fever and nausea 
• Generally feeling unwell 
• Shivering 
• Sweating 



31 

 
Uncommon (affects 1 to 10 users in 1.000): 
• Flu like symptoms 
• Urticaria (hives). 
 
Rare (affects 1 to 10 users in 10.000): 
• Convulsions 
• Eye swelling  
• 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 AFLUNOV. These side effects may occur with AFLUNOV.  
 
• Generalised skin reactions including  

• Itching 
• Urticaria (hives) 
• Rash or swelling of the skin and mucous membranes 
• Angioedema (abnormal swelling of the skin, usually around the eyes, lips, tongue, hands 

or feet, due to an allergic reaction). 
 
• 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. 

 



32 

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 
AFLUNOV. 
 
• 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 AFLUNOV 
 
Keep this vaccine out of the sight and reach of children. 
 
Do not use AFLUNOV after the expiry date which is stated on the carton and the label. The expiry 
date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C).  
Do not freeze.  
Store in the original package in order to protect from light. 
 
Do not throw 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 AFLUNOV contains 
 
- Active Substance: 

Influenza virus surface antigens (haemagglutinin and neuraminidase)* of strain: 
 
A/turkey/Turkey/1/2005 (H5N1)-like strain (NIBRG-23) (clade 2.2.1) 7.5 micrograms** 
per 0.5 ml dose 
 
* propagated in fertilised hens’ eggs from healthy chicken flocks 
** expressed in microgram haemagglutinin. 
 

- Adjuvant MF59C.1: 
The vaccine contains per 0.5 ml 9.75 mg squalene, 1.175 mg polysorbate 80, 1.175 mg sorbitan 
trioleate.  
 



33 

- Other ingredients: 
The other ingredients are: sodium chloride, potassium chloride, potassium dihydrogen 
phosphate, disodium phosphate dihydrate, magnesium chloride hexahydrate, calcium 
chloride dihydrate, sodium citrate, citric acid and water for injections. 
 

 
What AFLUNOV looks like and contents of the pack 
 
AFLUNOV is a suspension for injection in a pre-filled syringe. 
The suspension is a milky-white liquid. 
It is provided in a ready-to-use pre-filled syringe, containing a single dose of 0.5 ml for injection. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
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} 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER 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
	A. LABELLING
	B. PACKAGE LEAFLET