Flucelvax Tetra

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
  



 

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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Flucelvax Tetra - suspension for injection in pre-filled syringe 
Influenza vaccine (surface antigen, inactivated, prepared in cell cultures) 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Influenza virus surface antigens (haemagglutinin and neuraminidase), inactivated, of the following 
strains*: 
 
A/Hawaii/70/2019 (H1N1)pdm09-like strain (A/Nebraska/14/2019, wild type) 15 micrograms HA** 

A/Hong Kong/45/2019 (H3N2)-like strain (A/Delaware/39/2019, wild type) 15 micrograms HA** 

B/Washington/02/2019-like strain (B/Darwin/7/2019, wild type) 15 micrograms HA** 
B/Phuket/3073/2013-like strain (B/Singapore/INFTT-16-0610/2016, wild type) 15 micrograms HA** 
 
per 0.5 ml dose 
………………………………………. 
* propagated in Madin Darby Canine Kidney (MDCK) cells 
** haemagglutinin 
 
The vaccine complies with the World Health Organisation (WHO) recommendation (northern 
hemisphere) and EU recommendation for the 2020/2021 season. 
 
Flucelvax Tetra may contain traces of beta-propiolactone, cetyltrimethylammonium bromide, and 
polysorbate 80.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection in pre-filled syringe (injection). 
Clear to slightly opalescent liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Prophylaxis of influenza in adults and children from 9 years of age.  
 
Flucelvax Tetra should be used in accordance with official recommendations. 
 



 

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4.2 Posology and method of administration 
 
Posology 
 
Adults and children from 9 years of age: 
 
A single 0.5 ml dose.  
 
The safety and efficacy of Flucelvax Tetra in children from birth to less than 9 years of age has not 
been established. Currently available safety and immunogenicity data are described in sections 4.8 and 
5.1 but no recommendation on posology can be made. 
 
Method of administration  

For intramuscular injection only.  
The preferred site for injection is the deltoid muscle of the upper arm.  
 
The vaccine must not be injected intravenously, subcutaneously or intradermally and must not be 
mixed with other vaccines in the same syringe. 
 
For instructions on the handling of the vaccine before administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, to any of the excipients listed in section 6.1, or to possible 
trace residues such as beta-propiolactone, cetyltrimethylammonium bromide, and polysorbate 80. 
 
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. 
 
Appropriate medical treatment and supervision should always be readily available in case of a rare 
anaphylactic event following the administration of the vaccine. 
 
Vaccination should be postponed in patients with acute febrile illness until the fever is resolved.  
 
As with all injectable vaccines, Flucelvax Tetra must be administered with caution to individuals with 
thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular 
administration. 
 
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. 
 
Antibody response in patients with endogenous or iatrogenic immunosuppression may be insufficient 
to prevent influenza. 
 
A protective immune response may not be elicited in all vaccine recipients. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed with Flucelvax Tetra. There are no data available on co-
administration of Flucelvax Tetra with other vaccines. Based on clinical experience with cell-based 
trivalent influenza vaccine (TIVc), Flucelvax Tetra can be given at the same time as other vaccines. 



 

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4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are limited data from the use of Flucelvax Tetra in pregnant women. However, inactivated 
influenza vaccines can be used in all stages of pregnancy. For egg-derived influenza vaccines larger 
datasets on safety are available for the second and third trimester, compared with the first trimester; 
however, data from worldwide use of influenza vaccine do not indicate any adverse foetal and 
maternal outcomes attributable to the vaccine. 
 
There are no reproductive and developmental toxicology studies with Flucelvax Tetra. Reproductive 
and developmental toxicology data from cell-based trivalent influenza vaccine (TIVc) do not predict 
an increased risk of developmental abnormalities. 
 
Breast-feeding 
It is unknown whether Flucelvax Tetra is excreted in human milk. No effects on breast fed 
newborn/infant are anticipated. Flucelvax Tetra may be used during lactation. 
 
Fertility 
No human fertility data are available. Animal data, with cell-based trivalent influenza vaccine (TIVc), 
have not shown effects on female fertility. Male fertility has not been assessed in animals. 
 
4.7 Effects on ability to drive and use machines 
 
Flucelvax Tetra has no or negligible influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety of Flucelvax Tetra in adults 18 years and older was evaluated in a randomised, controlled 
study (V130_01), in which 1334 subjects received Flucelvax Tetra. Similar rates of solicited local and 
systemic adverse reactions were reported in subjects who received Flucelvax Tetra and cell-based 
trivalent influenza vaccine comparator in this clinical trial. 
 
The most commonly reported (≥10%) reactions in subjects who received Flucelvax Tetra were pain at 
the injection site (34%), headache (14%), fatigue (14%), myalgia (14%), erythema (13%) and 
induration (10%). 
 
The incidence of some adverse reactions were considerably lower among subjects ≥ 65 years of age 
when compared to subjects 18 to < 65 years of age (see table below).  
 
Tabulated list of adverse reactions 
 
Adverse reactions reported are listed according to the following frequency categories: Very common 
(≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100), not known (cannot be estimated 
from the available data). 
 



 

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Table 1:  Adverse reactions reported following vaccination in adults 18 years and older in 
clinical trials and post-marketing surveilance. 

MedDRA System Organ class Very common 
(≥1/10) 

Common 
(≥1/100 to <1/10) 

Uncommon 
(≥1/1,000 to 

<1/100) 

Frequency  
not known3 

Immune system disorders    Allergic or 
immediate 
hypersensitivity 
reactions, including 
anaphylactic shock 

Metabolism and nutrition 
disorders 

 Loss of appetite   

Nervous system disorders Headache1   Paraesthesia 

Gastrointestinal disorders  Nausea,  
Diarrhoea,  
Vomiting2 

  

Skin and subcutaneous tissue 
disorders 

   Generalised skin 
reactions including 
pruritus, urticaria or 
non-specific rash 

Musculoskeletal and 
connective tissue disorders 

Myalgia1 Arthralgia   

General disorders and 
administration site conditions 

Injection site pain, 
Fatigue1,  
Erythema, 
Induration1  

Ecchymosis,  
Chills 

Fever (≥ 38°C) Extensive swelling 
of injected limb   

1 Reported as Common in the elderly population 65 years of age and older 
2 Reported as Uncommon in the elderly population 65 years of age and older 
3 Adverse reactions reported from post-marketing surveillance 
 
Paediatric population (9 to less than 18 years of age) 
 
The safety of Flucelvax Tetra in children 4 to less than 18 years of age was evaluated in a randomised, 
controlled study (V130_03). In this study, 1159 paediatric subjects received Flucelvax Tetra (584 
subjects aged > 9 to < 18 years; 575 subjects aged > 4 to < 9 years). Children 9 to less than 18 years of 
age received a single dose of Flucelvax Tetra. Children 4 to less than 9 years of age received one or 
two doses (separated by 4 weeks) of Flucelvax Tetra based on determination of the subject’s prior 
influenza vaccination history. In this age group, 235 paediatric subjects received one dose and 340 
subjects received two doses. Similar rates of solicited local and systemic adverse reactions were 
reported in subjects who received Flucelvax Tetra and cell-based trivalent influenza vaccine 
comparator in this clinical trial.  
 
The most common (≥10%) adverse reactions reported in paediatric subjects of 9  to  < 18 years of age 
were injection site pain (58%), headache (22%), erythema (19%), fatigue (18%), myalgia (16%), and 
induration (15%). Similar rates of local and system adverse reactions were reported in the overall 
paediatric population 4 to < 18 years of age. 
 
Compared to adults 18 years of age and older, paediatric subjects generally reported higher rates of local 
and systemic adverse reactions. 
 



 

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Paediatric Population (4 to less than 9 years of age) 
 
Flucelvax Tetra is not indicated for use in children less than 9 years of age, see section 4.2. The available 
safety data in the paediatric population are presented below. 
 
Children less than 9 years of age reported similar rates of adverse reactions compared to older children.  
 
In the paediatric population 4 to less than 6 years of age, the following additional solicited adverse 
reactions were reported: sleepiness (21%), irritability (19%) and change in eating habits (14%). 
 
In children who received a second dose of Flucelvax Tetra or cell-based trivalent influenza vaccine, the 
incidence of adverse reactions following the second dose of vaccine was similar to that observed with 
the first dose in this clinical trial. 
 
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 
 
There are no data for overdose with Flucelvax Tetra. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Influenza vaccine, ATC code: J07BB02 
 
Mechanism of action 
 
Flucelvax Tetra provides active immunisation against four influenza virus strains (two A subtypes and 
two B types) contained in the vaccine. Flucelvax Tetra induces humoral antibodies against the 
haemagglutinins. These antibodies neutralise influenza viruses. 
 
Flucelvax Tetra is manufactured using Madin Darby Canine Kidney (MDCK) cells. 
 
Specific levels of haemagglutination inhibition (HI) antibody titres post-vaccination with inactivated 
influenza vaccine have not been correlated with protection from influenza virus. In some human 
studies, antibody titres of 1:40 or greater have been associated with protection from influenza illness in 
up to 50% of subjects. 
 
Antibody against one influenza virus type or subtype confers limited or no protection against another. 
Furthermore, antibody to one antigenic variant of influenza virus might not protect against a new 
antigenic variant of the same type or subtype.  
 
Annual revaccination with current influenza vaccines is recommended because immunity declines 
during the year after vaccination and circulating strains of influenza virus may change from year to 
year. 
 

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


 

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Pharmacodynamic effects 
 
Immunogenicity of Flucelvax Tetra in Adults 18 years of age and older 
Immunogenicity of Flucelvax Tetra was evaluated in adults 18 years of age and older in a randomised, 
double-blind, controlled study (V130_01). In this study, subjects received Flucelvax Tetra (N = 1334) 
or one of the two formulations of comparator cell-based trivalent influenza vaccine (TIVc) [TIV1c 
(N = 677) or TIV2c (N = 669)]. The immune response to each of the vaccine antigens was assessed, 
21 days after vaccination. 
 
The immunogenicity endpoints were geometric mean antibody titres (GMTs) of haemagglutination 
inhibition (HI) antibodies response and percentage of subjects who achieved seroconversions, defined 
as a pre-vaccination HI titre of <1:10 with a post vaccination titre ≥1:40 or with a prevaccination HI 
titre of ≥10 and a minimum 4-fold increase in serum HI antibody titre. 
 
Flucelvax Tetra was non-inferior to TIVc. Non-inferiority was established for all 4 influenza strains 
included in Flucelvax Tetra, as assessed by ratios of GMTs and the differences in the percentages of 
subjects achieving seroconversion at 3 weeks following vaccination. The antibody response to 
influenza B strains contained in Flucelvax Tetra was superior to the antibody response after 
vaccination with TIVc containing an influenza B strain from the alternate lineage. There was no 
evidence that the addition of the second influenza B strain resulted in immune interference to other 
strains included in the vaccine. 
 
Age subgroup analyses in subjects 18 to less than 65 years of age and 65 years of age and above 
confirmed that HI antibody responses (GMT and differences in vaccine group seroconversion rates) 
met non-inferiority immunogenicity criteria 3 weeks following vaccination for all 4 influenza strains 
in both age groups. 
 
The non-inferiority data observed are summarised in Table 2. 
 
Table 2:  Noninferiority of Flucelvax Tetra relative to TIVc in adults 18 years of age and above 

– Per protocol analysis set (V130_01) 
 

 

Flucelvax Tetra 
N = 1250 

TIV1c/TIV2ca 
N = 635/N = 639 

Vaccine Group 
Ratio 

(95% CI) 

Vaccine 
Group 

Difference 
(95% CI) 

A
/H

1N
1 GMT 

(95% CI) 
302.8 

(281.8-325.5) 
298.9 

(270.3-330.5) 
1.0 

(0.9-1.1) - 

Seroconversion 
Rateb (95% CI) 

49.2% 
(46.4-52.0) 

48.7% 
(44.7-52.6) - 

-0.5% 
(-5.3-4.2) 

A
/H

3N
2 GMT 

(95% CI) 
372.3 

(349.2-396.9) 
378.4 

(345.1-414.8) 
1.0 

(0.9-1.1) - 

Seroconversion 
Rateb (95% CI) 

38.3% 
(35.6-41.1) 

35.6% 
(31.9-39.5) - 

-2.7% 
(-7.2-1.9) 

B
1 

GMT 
(95% CI) 

133.2 
(125.3-141.7) 

115.6 
(106.4-125.6) 

0.9 
(0.8-1.0) - 

Seroconversion 
Rateb (95% CI) 

36.6% 
(33.9-39.3) 

34.8% 
(31.1-38.7) - 

-1.8% 
(-6.2-2.8) 

B
2 

GMT 
(95% CI) 

177.2 
(167.6-187.5) 

164.0 
(151.4-177.7) 

0.9 
(0.9-1.0) - 

Seroconversion 
Rateb (95% CI) 

39.8% 
(37.0-42.5) 

35.4% 
(31.7-39.2) - 

-4.4% 
(-8.9-0.2) 

Abbreviations: GMT = geometric mean titre; CI = confidence interval.  
a The comparator vaccine for noninferiority comparisons for A/H1N1, A/H3N2 and B1 is TIV1c, for B2 it is 
TIV2c. 
b Seroconversion rate = percentage of subjects with either a pre-vaccination HI titre <1:10 and post-vaccination 
HI titre ≥1:40 or with a pre-vaccination HI titre ≥1:10 and a minimum 4-fold increase in post-vaccination HI 
antibody titre. 



 

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Bold = Non-inferiority criterion met. 
 
Clinical efficacy of cell-based trivalent influenza vaccine (TIVc) against culture-confirmed influenza 
in adults 
 
The efficacy experience with TIVc is relevant to Flucelvax Tetra because both vaccines are 
manufactured using the same process and have overlapping compositions.  
 
A multinational, randomised, observer-blinded, placebo-controlled trial (V58P13) was performed to 
assess clinical efficacy and safety of TIVc during the 2007-2008 influenza season in adults aged 18 to 
less than 50 years. A total of 11,404 subjects were enrolled to receive TIVc (N = 3828), Agrippal 
(N = 3676) or placebo (N = 3900) in a 1:1:1 ratio.  

TIVc efficacy was defined as the prevention of culture-confirmed symptomatic influenza illness 
caused by viruses antigenically matched to those in the vaccine compared to placebo. Influenza cases 
were identified by active and passive surveillance of influenza-like illness (ILI). ILI was defined 
according to Centers for Disease Control and Prevention (CDC) case definition, i.e., a fever (oral 
temperature ≥100.0°F / 38°C) and cough or sore throat. After an episode of ILI, nose and throat swab 
samples were collected for analysis. Vaccine efficacies against vaccine-matched influenza viral 
strains, against all influenza viral strains, and against individual influenza viral subtypes were 
calculated (Table 3). 
 
Table 3:  Comparative efficacy of TIVc versus placebo against culture-confirmed influenza by 

influenza viral subtype (V58P13) 
 TIVc 

(N = 3776) 
Placebo 

(N = 3843) 
Vaccine Efficacy* 

 Attack Rate 
(%) 

Number of 
Subjects with 

Influenza 

Attack Rate 
(%) 

Number of 
Subjects with 

Influenza 

% Lower Limit 
of One-

Sided 97.5% 
CI 

Antigenically Matched Strains 

Overall 0.19 7 1.14 44 83.8 61.0 

Individual 
strains 

A/H3N2** 0.05  2 0 0 -- -- 

A/H1N1 0.13 5 1.12 43 88.2 67.4 

B** 0 0 0.03 1 -- -- 

All Culture-Confirmed Influenza 

Overall 1.11 42 3.64 140 69.5 55.0 

Individual 
strains 

A/H3N2 0.16 6 0.65 25 75.6 35.1 

A/H1N1 0.16 6 1.48 57 89.3 73.0 

B 0.79 30 1.59 61 49.9 18.2 
*  Simultaneous one-sided 97.5% confidence intervals for the vaccine efficacy of each influenza vaccine 

relative to placebo based on the Sidak-corrected score confidence intervals for the two relative risks.  
Vaccine Efficacy = (1 - Relative Risk) x 100%; 

**  There were too few cases of influenza due to vaccine-matched influenza A/H3N2 or B to adequately assess 
vaccine efficacy. 

 
Paediatric population  
 
Immunogenicity of Flucelvax Tetra in Children and Adolescents 9 to less than 18 Years of Age 
 
Immunogenicity of Flucelvax Tetra was evaluated in children 9 to less than 18 years of age as part of a 
randomised, double-blind, controlled study (V130_03) that was performed in the paediatric population 
4 to less than 18 years of age. In this study, subjects received Flucelvax Tetra (N = 1159) or one of the 
two formulations of comparator cell-based trivalent influenza vaccine (TIVc) [TIV1c (N = 593), or 



 

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TIV2c (N = 580)]. The immune response to each of the vaccine antigens was assessed 21 days after 
vaccination. 
The immunogenicity endpoints were GMTs of HI antibodies response and percentage of subjects who 
achieved seroconversions (seroconversion rate), defined as a pre-vaccination HI titre of <1:10 with a 
post-vaccination titre ≥1:40 or with a pre-vaccination HI titre ≥ 1:10 and a minimum 4-fold increase in 
serum HI antibody titre. 
 
Flucelvax Tetra was noninferior to TIVc in children 4 to less than 18 years of age. Non-inferiority was 
established for all 4 influenza strains included in the Flucelvax Tetra, as assessed by ratios of GMTs 
and the differences in the percentages of subjects achieving seroconversion at 3 weeks following 
vaccination. The antibody response to influenza B strains contained in Flucelvax Tetra was superior to 
the antibody response after vaccination with TIVc containing an influenza B strain from the alternate 
lineage. There was no evidence that the addition of the second B strain resulted in immune 
interference to other strains included in the vaccine. 
 
The immunogenicity data in subjects 9 to less than 18 years of age are summarised in Table 4. 
 
Table 4:  GMTs and seroconversion rates (with 95% CI) in subjects 9 to <18 years of age, 

3 weeks after vaccination with Flucelvax Tetra or TIV1c/TIV2c - Per Protocol Set 
(V130_03) 

  Flucelvax Tetra TIV1c/TIV2ca 

A
/H

1N
1  N = 547 N = 272 

GMT (95% CI) 1139 (1045-1242) 1138 (1007-1286) 
Seroconversion Rateb 70% (66%-74%) 72% (67%-78%) 

A
/H

3N
2  N = 546 N = 272 

GMT (95% CI) 719 (673-767) 762 (694-836) 
Seroconversion Rateb 42% (38%-47%) 53% (46%-59%) 

B
1 

 N = 546 N = 272 

GMT (95% CI) 200 (185-218) 200 (178-224) 
Seroconversion Rateb 63% (58%-67%) 63% (57%-69%) 

B
2 

 N = 545 N = 265 

GMT (95% CI) 212 (192-235) 203 (175-234) 
Seroconversion Rateb 72% (68%-75%) 68% (62%-74%) 

a For H1N1, H3N2 and B1 influenza strains TIV1c data are presented, whereas for B2 influenza strain TIV2c 
data are presented. 
b Seroconversion rate = percentage of subjects with either a pre-vaccination HI titre <1:10 and post-vaccination 
HI titre ≥1:40 or with a pre-vaccination HI titre ≥1:10 and a minimum 4-fold increase in post-vaccination HI 
antibody titre. 
Bold- CHMP immunogenicity criteria met. The percentage of subjects with seroconversion or significant 
increase in HI antibody titre is >40%, the percentage of subjects achieving an HI titre ≥1:40 is >70%. 
 
 
Comparison of immunogenicity of TIVc in the paediatric and adult population 
 
The immunogenicity data with TIVc are relevant to the use of Flucelvax Tetra because both vaccines 
are manufactured using the same process and have overlapping compositions. Immunogenicity of 
TIVc in children 9 to less than 18 years of age was evaluated as part of a randomised, double-blind, 
controlled study (V58P12) that was performed in the paediatric population 3 to less than 18 years of 
age. Immune responses following vaccination with TIVc in the paediatric population (9  to < 18 years) 
were similar to those observed in the adult population in study V58P13 (see Table 5) in whom efficacy 
was demonstrated (results on vaccine efficacy are presented in Table 3). It should be noted that both 
V58P12 and V58P13 were performed in the 2007-2008 northern hemisphere influenza season. 
 



 

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Table 5:  GMTs and seroconversion rates in adult and paediatric subjects vaccinated with 
TIVc (V58P12 and V58P13) 

 

 

V58P12  
(Subjects 9 to < 18 years) 

V58P13 
(Subjects 18 to < 50 years) 

TIVc  TIVeF  TIVc  TIVeA  

N = 142 N = 144 N = 228 N = 695 

A
/H

1N
1 

GMT (95% CI) 879 (728-1062) 1107 (918-1334) 566 (483-663) 499 (455-546) 

Seroconversion Ratea 77% (70%-84%) 77% (69-84) 78% (72%-83%) 75% (71%-78%) 

A
/H

3N
2 

GMT (95% CI) 706 (607-821) 1857 (1598-2157) 332 (289-383) 357 (330-387) 

Seroconversion Ratea 56% (48%-65%) 77% (69-84) 59% (53%-66%) 68% (64%-71%) 

B
 GMT (95% CI) 58 (48-71) 105 (86-129) 72 (63-84) 120 (111-131) 

Seroconversion Ratea 56% (48%-65%) 71% (63-78) 51% (45%-58%) 68% (65%-73%) 
HI data, egg-derived assay 
TIVc = cell-based trivalent influenza vaccine; TIVeA = egg-based trivalent influenza vaccine (Agrippal); 
TIVeF = egg-based trivalent influenza vaccine (Fluvirin) 
a Seroconversion rate = percentage of subjects with either a pre-vaccination HI titre <1:10 and post-vaccination 
HI titre ≥1:40 or with a pre-vaccination HI titre ≥1:10 and a minimum 4-fold increase in post-vaccination HI 
antibody titre. 
 
 
Immunogenicity of Flucelvax Tetra in children 4 to less than 9 years of age 
 
Flucelvax Tetra is not indicated for use in children less than 9 years of age, see Section 4.2. The available 
immunogenicity data in the paediatric population 4 to less than 9 years of age were obtained in trial 
V130_03. Overall, the immunogenicity results were in line with those obtained in subjects older than 9 
years of age and showed a similar immune response in subjects receiving Flucelvax Tetra as compared 
to those receiving a comparator TIVc. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Flucelvax Tetra in children 6 months to 4 years of age in the prevention of influenza.  
 
5.2 Pharmacokinetic properties 
 
Not applicable. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose 
toxicity and toxicity to reproduction and development.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium chloride 
Potassium chloride 
Magnesium chloride hexahydrate 
Disodium phosphate dihydrate 
Potassium dihydrogen phosphate 
Water for injections 
 



 

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6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.  
 
6.3 Shelf life 
 
12 months 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
Keep the pre filled syringe in the outer carton in order to protect from light. 
 
6.5 Nature and contents of container  
 
0.5 ml suspension in pre-filled syringes (type I glass), with a plunger stopper (bromobutyl rubber), 
with or without needle.  
 
Pack of 1 pre-filled syringe, with or without needle 
Pack of 10 pre-filled syringes, with or without needles. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Shake before use. After shaking, the normal appearance of the vaccine is a clear to slightly opalescent 
suspension. 
 
The vaccine should be visually inspected for particulate matter and discoloration prior to 
administration. In the event of any foreign particulate matter and/or variation of physical aspect is 
observed, do not administer the vaccine. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Seqirus Netherlands B.V. 
Paasheuvelweg 28  
1105BJ Amsterdam 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1326/001 
EU/1/18/1326/002 
EU/1/18/1326/003 
EU/1/18/1326/004 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 12 December 2018 
 



 

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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/


 

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ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) 
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 
 

 



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

Name and address of the manufacturer(s) of the biological active substance(s) 
Seqirus Inc. 
475 Green Oaks Parkway 
Holly Springs 
NC 27540 
United States 

Name and address of the manufacturer(s) responsible for batch release 
Seqirus Vaccines Ltd 
Gaskill Road 
Speke 
Liverpool 
L24 9GR 
United Kingdom 

  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 
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. 

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;



 

15 

• 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.  

 
  



 

16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX III 

 
LABELLING AND PACKAGE LEAFLET 

  



 

17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
A. LABELLING 

  



 

18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
Carton box for syringe(s) with needle: 
- 1 pre-filled syringe (0.5 ml) with needle 
- 10 pre-filled syringes (0.5 ml) with needle 
Carton box for syringe(s) without needle: 
- 1 pre-filled syringe (0.5 ml) without needle 
- 10 pre-filled syringes (0.5 ml) without needle 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Flucelvax Tetra suspension for injection in pre-filled syringe 
Influenza vaccine (surface antigen, inactivated, prepared in cell cultures) 
2020/2021 season 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Influenza virus surface antigens (haemagglutinin and neuraminidase), inactivated, of the following 
strains*: 
 
A/Hawaii/70/2019 (H1N1)pdm09-like strain 15 micrograms HA** 

A/Hong Kong/45/2019 (H3N2)-like strain 15 micrograms HA** 

B/Washington/02/2019-like strain 15 micrograms HA** 
B/Phuket/3073/2013-like strain 15 micrograms HA** 
 
per 0.5 ml dose 
………………………………………. 
* propagated in Madin Darby Canine Kidney (MDCK) cells 
** haemagglutinin 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium chloride, potassium chloride, magnesium chloride hexahydrate, disodium phosphate 
dihydrate, potassium dihydrogen phosphate and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in pre-filled syringe 
 
10 pre-filled syringes (0.5 ml) without needle 
1 pre-filled syringe (0.5 ml) with needle 
10 pre-filled syringes (0.5 ml) with needle 
1 pre-filled syringe (0.5 ml) without needle 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use. 
 
Read the package leaflet before use. 
 
 



 

19 

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. 
Keep the pre filled syringe in the outer carton 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 

 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Seqirus Netherlands B.V. 
Paasheuvelweg 28 
1105BJ Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1326/001  10 pre filled syringes without needle 
EU/1/18/1326/002  1 pre filled syringe with needle 
EU/1/18/1326/003  10 pre filled syringes with needle 
EU/1/18/1326/004 1 pre filled syringe without needle 
 
13. BATCH NUMBER 
 
Lot: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
Shake before use. 



 

20 

 
 
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  



 

21 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pre-filled syringe label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Flucelvax Tetra injection 
Influenza vaccine 
2020/2021 season 
 
 
2. METHOD OF ADMINISTRATION 
 
i.m. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot:  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
0.5 ml 
 
 
6. OTHER 
 
 
 
  



 

22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 



 

23 

Package leaflet: Information for the user 
 
 

Flucelvax Tetra - suspension for injection in pre-filled syringe 
Influenza vaccine (surface antigen, inactivated, prepared in cell cultures) 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you receive this medicine 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, pharmacist or nurse. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Flucelvax Tetra is and what it is used for  
2. What you need to know before you receive Flucelvax Tetra  
3. How Flucelvax Tetra is given  
4. Possible side effects  
5. How to store Flucelvax Tetra   
6. Contents of the pack and other information 
 
 
1. What Flucelvax Tetra is and what it is used for 
 
Flucelvax Tetra is a vaccine against flu (influenza). Flucelvax Tetra is prepared in cell cultures, and, 
therefore, is egg-free. 
When a person is given the vaccine, the immune system (the body’s natural defence system) will 
produce its own protection against the influenza virus. None of the ingredients in the vaccine can 
cause flu. 
 
Flucelvax Tetra is used to prevent flu in adults and children from 9 years of age. 
 
The vaccine targets four strains of influenza virus following the recommendations by the World 
Health Organisation for the 2020/2021 season. 
 
 
2. What you need to know before you receive Flucelvax Tetra 
 
You should not receive Flucelvax Tetra: 
If you are allergic to: 

• the active ingredients or any of the other ingredients of this medicine (listed in section 6) 
• beta-propiolactone, cetyltrimethylammonium bromide, or polysorbate 80, which are trace 

residues from the manufacturing process. 
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before receiving Flucelvax Tetra. 
 
BEFORE receiving the vaccine 
• Your doctor or nurse will make sure that appropriate medical treatment and supervision is readily 

available in case of a rare anaphylactic reaction (a very severe allergic reaction with symptoms 



 

24 

such as difficulty in breathing, dizziness, a weak and rapid pulse and skin rash) following the 
administration. This reaction may occur with Flucelvax Tetra as with all vaccines that are injected. 

• You should tell your doctor if you have an acute illness associated with fever. Your doctor may 
decide to delay your vaccination until your fever is gone. 

• You should tell your doctor if your immune system is impaired, or if you are undergoing treatment 
which affects the immune system, e.g. with medicine against cancer (chemotherapy) or 
corticosteroid medicines (see section “Other medicines and Flucelvax Tetra”). 

• You should tell your doctor 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. 
 
As with all vaccines, Flucelvax Tetra may not fully protect all persons who are vaccinated. 
 
Other medicines and Flucelvax Tetra  
Tell your doctor or nurse if you are using, have recently used or might use any other medicines, 
including medicines obtained without a prescription or if you have recently received any other 
vaccine. 
 
Flucelvax Tetra may be given at the same time as other vaccines. 
 
Pregnancy and breast-feeding  
Pregnancy: 
Tell your doctor if you are pregnant, think you may be pregnant or are planning to have a baby. 
Influenza vaccinations can be used at any stage of pregnancy.  
 
Breast-feeding: 
Use of Flucelvax Tetra during breast-feeding has not been studied. Flucelvax Tetra may be used 
during breast-feeding. 
 
Driving and using machines 
Flucelvax Tetra has no or negligible effect on your ability to drive and use machines. 
 
Flucelvax Tetra contains sodium chloride and potassium chloride 
This vaccine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium free’. 
This vaccine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially ‘potassium free’. 
 
 
3. How Flucelvax Tetra is given 
 
Flucelvax Tetra is given to you by your doctor or nurse as an injection into the muscle at the top of the 
upper arm (deltoid muscle). 
 
Adults and children from 9 years of age: 
 
One dose of 0.5 ml 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
The following side effects have been reported during clinical trials and during general use: 
 
Very serious side effects 
Tell your doctor immediately or go to the casualty department at your nearest hospital if you 
experience the following side effect – you may need urgent medical attention or hospitalisation: 
 



 

25 

• difficulty in breathing, dizziness, a weak and rapid pulse and skin rash which are symptoms of an 
anaphylactic reaction (a very severe allergic reaction) 
 

Serious side effects 
Tell your doctor immediately if you experience any of the following side effects – you may need 
medical attention: 
 
• Extensive swelling of injected limb 
 
Mild side effects 
Very common (may affect more than 1 in 10 people): 
• Injection site pain, reddening, hardening or swelling at the site of the injection 
• Headache 
• Muscle pain  
• Tiredness 
Hardening or swelling at the site of the injection, headache, muscle pain, and fatigue were common in 
the elderly. 
 
Common (may affect up to 1 in 10 people): 
• Nausea, vomiting, diarrhoea  
• Loss of appetite 
• Joint pain 
• Bruising 
• Shivering 
Vomiting was uncommon in the elderly  
 
Uncommon (may affect up to 1 in 100 people): 
• Fever (> 38°C) 
Fever was common in adolescents and children.  
 
Not known (cannot be estimated from the available data): 
• Numbness and tingling sensation 
• Generalised skin reactions including itching, bumps on the skin or non-specific rash 
 
Reporting of side effects 
If you get any side effects, talk to your healthcare professional. 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 Flucelvax Tetra  
 
Keep this vaccine out of the sight and reach of children. 
 
Store in a refrigerator (2 °C to 8 °C). Do not freeze. 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
 
Do not use this vaccine after the expiry date, which is stated on the label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
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 protect the environment. 
 
 

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


 

26 

6. Contents of the pack and other information 
 
What Flucelvax Tetra contains  
 
- The active substances are influenza virus surface antigens (haemagglutinin and neuraminidase), 

inactivated, of the following strains*: 
 

A/Hawaii/70/2019 (H1N1)pdm09-like strain (A/Nebraska/14/2019, wild type) 15 micrograms 
HA** 
A/Hong Kong/45/2019 (H3N2)-like strain (A/Delaware/39/2019, wild type) 15 micrograms 
HA** 
B/Washington/02/2019-like strain (B/Darwin/7/2019, wild type) 15 micrograms HA** 
B/Phuket/3073/2013-like strain (B/Singapore/INFTT-16-0610/2016, wild type) 15 micrograms 
HA** 
 
per 0.5 ml dose 
………………………………………. 
* propagated in Madin Darby Canine Kidney (MDCK) cells (this is the special cell culture 

in which the influenza virus is grown);  
** haemagglutinin 

 
This vaccine complies with the World Health Organisation (WHO) recommendation (northern 
hemisphere) and EU recommendation for the 2020/2021 season. 
 
- The other ingredients are: sodium chloride, potassium chloride, magnesium chloride hexahydrate, 

disodium phosphate dihydrate, potassium dihydrogen phosphate and water for injections. 
 
What Flucelvax Tetra looks like and contents of the pack 
 
Flucelvax Tetra is a suspension for injection in a pre-filled syringe (ready to use syringe).  
Flucelvax Tetra is a clear to slightly opalescent suspension. 
A single syringe contains 0.5 ml of suspension for injection. 
Flucelvax Tetra is available in packs containing 1 pre-filled syringe with or without needle or 10 pre-
filled syringes with or without needles. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder  
Seqirus Netherlands B.V. 
Paasheuvelweg 28 
1105BJ Amsterdam 
Netherlands 
 
Manufacturer 
Seqirus Vaccines Limited 
Gaskill Road, Speke 
L24 9GR Liverpool 
United Kingdom 
 
Seqirus Netherlands B.V. 
Paasheuvelweg 28 
1105BJ Amsterdam 
Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 



 

27 

België/Belgique/Belgien 
Seqirus Netherlands B.V. 
Nederland/Netherlands 
Tel: +31 (0) 20 204 6900 
 
България 
Seqirus Netherlands B.V. Нидерландия 
Тел.: +31 (0) 20 204 6900 
 
Česká republika 
Seqirus Netherlands B.V. Nizozemsko 
Tel: +31 (0) 20 204 6900 
 
Danmark 
Seqirus Netherlands B.V. Holland 
Tlf: +31 (0) 20 204 6900 
 
Deutschland 
Seqirus GmbH Marburg 
Tel: 08003601010 
 
Eesti 
Seqirus Netherlands B.V. Holland 
Tel: +31 (0) 20 204 6900 
 
Ελλάδα 
Seqirus Netherlands B.V. Ολλανδία 
Τηλ: +31 (0) 20 204 6900 
 
España 
Seqirus Spain, S.L., Barcelona 
Tel: 937 817 884 
 
France 
Seqirus Netherlands B.V. Netherlands 
Tél: +31 (0) 20 204 6900 
 
Hrvatska 
Seqirus Netherlands B.V. Nizozemska 
Tel: +31 (0) 20 204 6900 
 
Ireland 
Seqirus UK Limited Maidenhead 
Tel: +44 1628 641 500 
 
Ísland 
Seqirus Netherlands B.V. Holland 
Sími: +31 (0) 20 204 6900 
 
Italia 
Seqirus S.r.l. Siena 
Tel: +39 0577 096400 
 
Κύπρος 
Seqirus Netherlands B.V. Ολλανδία 
Τηλ: +31 (0) 20 204 6900 

Lietuva 
Seqirus Netherlands B.V. Nyderlandai 
Tel: +31 (0) 20 204 6900 
 
 
Luxembourg/Luxemburg 
Seqirus Netherlands B.V. Netherlands 
Tél/Tel: +31 (0) 20 204 6900 
 
Magyarország 
Seqirus Netherlands B.V. Hollandia 
Tel.: +31 (0) 20 204 6900 
 
Malta 
Seqirus Netherlands B.V. In-Netherlands 
Tel: +31 (0) 20 204 6900 
 
Nederland 
Seqirus Netherlands B.V. Amsterdam 
Tel: +31 (0) 20 204 6900 
 
Norge 
Seqirus Netherlands B.V. Nederland 
Tlf: +31 (0) 20 204 6900 
 
Österreich 
Valneva Austria GmbH, Wien 
Tel: +43 1 20620  
 
Polska 
Seqirus Netherlands B.V. Holandia 
Tel.: +31 (0) 20 204 6900 
 
Portugal 
Seqirus Netherlands B.V. Países Baixos 
Tel: +31 (0) 20 204 6900 
 
România 
Seqirus Netherlands B.V. Olanda 
Tel: +31 (0) 20 204 6900 
 
Slovenija 
Seqirus Netherlands B.V. Nizozemska 
Tel: +31 (0) 20 204 6900 
 
Slovenská republika 
Seqirus Netherlands B.V. Holandsko 
Tel: +31 (0) 20 204 6900 
 
Suomi/Finland 
Seqirus Netherlands B.V. Alankomaat 
Puh/Tel: +31 (0) 20 204 6900 
 
Sverige 
Seqirus Netherlands B.V. Nederländerna 
Tel: +31 (0) 20 204 6900 



 

28 

 
Latvija 
Seqirus Netherlands B.V. Nīderlande 
Tel: +31 (0) 20 204 6900 
 

 
United Kingdom 
Seqirus UK Limited Maidenhead 
Tel: +44 1628 641 500 
 

 
 
This leaflet was last revised in  
 
Other sources of information 
 
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: 
 
Appropriate medical treatment and supervision should always be readily available in case of a rare 
anaphylactic event following the administration of the vaccine. 
 
Shake before use. After shaking, the normal appearance of the vaccine is a clear to slightly opalescent 
suspension. 
 
The vaccine should be visually inspected for particulate matter and discoloration prior to 
administration. In the event of any foreign particulate matter and/or variation of physical aspect being 
observed, do not administer the vaccine. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) 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
	A. LABELLING
	B. PACKAGE LEAFLET