Summary of medicine characteristics - Flucelvax Tetra
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/Wisconsin/588/2019 (H1N1)pdm09-like strain (A/Washington/19/2020, wild type) 15 micrograms HA
A/Cambodia/e0826360/2020 (H3N2)-like strain (A/Tasmania/503/2020, 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 2021/2022 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 PARTICULARS4.1 Therapeutic indications
Prophylaxis of influenza in adults and children from 2 years of age.
Flucelvax Tetra should be used in accordance with official recommendations.
4.2 Posology and method of administration
Posology
Adults and children from 2 years of age:
| Age Group | Dose | Schedule |
| 2 to < 9 years | One or twoa 0.5 mL doses | If 2 doses, administer at least 4 weeks apart |
| 9 years of age and older | One 0.5 mL dose | Not applicable |
a Children less than 9 years of age who have not been previously vaccinated against influenza, should receive a second dose.
The safety and efficacy of Flucelvax Tetra in children from birth to less than 2 years of age has not been established.
Method of administration
For intramuscular injection only.
The preferred site for injection is the deltoid muscle of the upper arm. Young children with insufficient deltoid mass should be vaccinated in the anterolateral aspect of the thigh.
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 coadministration 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.
4.6 Fertility, pregnancy and lactation
Pregnancy
Inactivated influenza vaccines, such as Flucelvax Tetra, can be given in any stage of pregnancy.
Larger safety datasets are available on vaccine use during the second or third trimester, compared with the first trimester; however, data from worldwide use of influenza vaccines do not indicate any adverse foetal and maternal outcomes attributable to the vaccine.
A prospective Pregnancy Exposure Registry was conducted in the United States (US) and data were collected from 665 women vaccinated with Flucelvax Tetra during 3 Northern Hemisphere influenza seasons (2017–18 to 2019–20), of whom 28% were exposed during their first trimester. Based on pregnancy outcomes and predefined infant safety outcomes, there was no evidence of adverse foetal, newborn or pregnancy outcomes attributable to the vaccine during any stage of pregnancy.
There have been 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 given 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).
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 (2 to less than 18 years of age)
The safety of Flucelvax Tetra in children 2 to less than 18 years of age has been evaluated in two clinical studies, V130_03 and V130_12. In the randomised, controlled study V130_03, 1159 paediatric subjects received Flucelvax Tetra (584 subjects 9 to <18 years; 575 subjects 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.
In the multinational, randomised, observer-blind study V130_12, the safety population included a total of 2255 children 2 to less than 18 years of age who received Flucelvax Tetra (580 subjects 2 to < 6 years; 564 subjects 6 to < 9 years; 1111 subjects 9 to < 18 years). Children 9 to less than 18 years of age received a single dose of Flucelvax Tetra. Children 2 to less than 9 years of age received one or two doses (separated by 28 days) of Flucelvax Tetra based on determination of the subject’s prior influenza vaccination history.
The most common local and systemic adverse reactions reported in either study is described below by paediatric sub-group.
The most common (>10%) local and systemic adverse reactions after one dose 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%).
The most common (>10%) local and systemic adverse reactions after any vaccination in children 6 to less than 9 years of age were pain at the injection site (61%), injection site erythema (25%), injection site induration (19%), fatigue (16%), headache (16%) and injection site ecchymosis (11%).
The most common (>10%) local and systemic adverse reactions after any vaccination in children 2 to less than 6 years of age were tenderness at the injection site (54%), injection site erythema (23%), sleepiness (21%), irritability (19%), injection site induration (15%), change in eating habits (14%) and injection site ecchymosis (11%).
Compared to adults 18 years of age and older, paediatric subjects generally reported higher rates of local and systemic adverse reactions.
In children who received a second dose of Flucelvax Tetra the incidence of adverse reactions following the second dose of vaccine was similar or slightly lower to that observed with the first dose.
The frequency of adverse reactions in children 2 to less and 18 years of age in these clinical studies are described in Table 2 below.
Table 2: Solicited adverse reactions reported in clinical studies in children 2 to < 18 years of age
| MedDRA System Organ class | Adverse Reactions | Frequency | ||
| 2 to < 9 years | 9 to < 18 years | |||
| 2 to < 6 1 | 6 to <9 | |||
| Metabolism and nutrition disorders | Loss of appetite | N/A | Very common | Common |
| Nervous system disorders | Headache | N/A | Very common | Very common |
| Gastrointestinal disorders | Diarrhoea | Common | Common | Common |
| Nausea | N/A | Common | Common | |
| Vomiting | Common | Common | Common | |
| Musculoskeletal and connective tissue disorders | Myalgia 2 | N/A | Very common | Very common |
| Arthralgia | N/A | Common | Common | |
| General disorders and administration site conditions | Injection site tenderness | Very common | N/A | N/A |
| Injection site pain | N/A | Very common | Very common | |
| Injection site erythema | Very common | Very common | Very common | |
| Injections site induration | Very common | Very common | Very common | |
| Injection site ecchymosis | Very common | Very Common | Common | |
| Sleepiness | Very common | N/A | N/A | |
| Irritability | Very common | N/A | N/A | |
| Fatigue | N/A | Very common | Very common | |
| Change in eating habits | Very common | N/A | N/A | |
| Chills/Shivering | Common | Common | Common | |
| Fever (>38° C) | Common | Common | Common | |
1 The youngest age range in study V130_03 was 4 to < 6 years
2 Myalgia reported with a frequency of Common (3% and 6%) in children 6 to < 9 and 9 to < 18 years, respectively, in study V130_12
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in
4.9 Overdose
There are no data for overdose with Flucelvax Tetra.
5. PHARMACOLOGICAL PROPERTIES5.1 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.
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 pre-vaccination 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 3.
Table 3: 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) | ||
| w | 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% C-5,3-4.2 ) | |
| A/H3N2 | 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 ) | |
| B1 | 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 ) | |
| B2 | 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.
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 4).
Table 4: 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 4 to less than 18 Years of Age
Immunogenicity of Flucelvax Tetra was evaluated in children 4 to less than 18 years of age as part of a randomised, double-blind, controlled study (V130_03). 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 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 4 to less than 18 years of age are summarised in Table 5.
Table 5: GMTs and seroconversion rates (with 95% CI) in subjects 4 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/H1N1 | N = 1014 | N = 510 | |
| GMT (95% CI) | 1090 (1027–1157) | 1125 (1034–1224) | |
| Seroconversion Rateb | 72% (69–75) | 75% (70–78) | |
| A/H3N2 | N = 1013 | N = 510 | |
| GMT (95% CI) | 738 (703–774) | 776 (725–831) | |
| Seroconversion Rateb | 47% (44–50) | 51% (46–55) | |
| B1 | N = 1013 | N = 510 | |
| GMT (95% CI) | 155 (146–165) | 154 (141–168) | |
| Seroconversion Rateb | 66% (63–69) | 66% (62–70) | |
| B2 | N = 1009 | N = 501 | |
| GMT (95% CI) | 185 (171–200) | 185 (166–207) | |
| Seroconversion Rateb | 73% (70–76) | 71% (67–75) |
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%.
Clinical efficacy of Flucelvax Tetra in the paediatric population 2 to less than 18 years of age
Absolute efficacy of Flucelvax Tetra was evaluated in children 2 to less than 18 years of age in Study V130_12. This was a multinational, randomised, non-influenza vaccine comparator-controlled efficacy study conducted in 8 countries over 3 influenza seasons, in which 4514 subjects were enrolled to received 0.5 ml of Flucelvax Tetra or a non-influenza comparator in a 1:1 ratio. Based on influenza vaccination history, participants received one or two doses (28 days apart) of the study vaccine.
Flucelvax Tetra efficacy was assessed by the prevention of confirmed influenza illness caused by any influenza Type A or B strain. Influenza cases were identified by active surveillance of influenza-like illness (ILI) and confirmed by viral culture and/or real-time polymerase chain reaction (RT-PCR). An ILI episode was defined as a fever body temperature > 37.8°C) along with at least one of the following: cough, sore throat, nasal congestion, or rhinorrhoea. Vaccine efficacy against laboratory confirmed influenza was calculated (Table 6).
Table 6: Number of Subjects with First-Occurrence RT-PCR Confirmed or Culture Confirmed Influenza and Absolute Vaccine Efficacy (95% CI), in Subjects 2 to less than 18 Years of Age- FAS Efficacy1 (Study V130_12)
| Number of subjects per protocol1 | Number of cases of influenza | Attack Rate (%) | Vaccine Efficacy (VE) | ||
| % | 95% CI of VE | ||||
| RT-PCR or Culture Confirmed Influenza | |||||
| Flucelvax Tetra | 2257 | 175 | 7.8 | 54.63 | 45.67, 62.12 |
| Non-Influenza Comparator | 2252 | 364 | 16.2 | – | – |
| Culture Confirmed Influenza | |||||
| Flucelvax Tetra | 2257 | 115 | 5.1 | 60.81 | 51.30, 68.46 |
| Non-Influenza Comparator | 2252 | 279 | 12.4 | – | – |
| Antigenically Matched Culture-Confirmed Influenza | |||||
| Flucelvax Tetra | 2257 | 90 | 4.0 | 63.64 | 53.64, 71.48 |
| Non-Influenza Comparator | 2252 | 236 | 10.5 | – | – |
1Number of subjects in the Full-Analysis Set (FAS)- Efficacy, which included all subjects randomised, received a study vaccination and provided efficacy data.
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 PARTICULARS6.1 List of excipients
Sodium chloride
Potassium chloride
Magnesium chloride hexahydrate
Disodium phosphate dihydrate
Potassium dihydrogen phosphate
Water for injections
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