Cell-based Trivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe

Prophylaxis of influenza in adults and children from 6 months of age.

Cell-based Trivalent Influenza Vaccine Seqirus should be used in accordance with official recommendations.

Posology

Adults and children from 6 months of age:

^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 Cell-based Trivalent Influenza Vaccine Seqirus in children from birth to less than 6 months 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.

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.

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 febrile illness until the fever is resolved.

As with all injectable vaccines, Cell-based Trivalent Influenza Seqirus 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.

Cell-based Trivalent Influenza Vaccine Seqirus can be given at the same time as other vaccines, including COVID vaccines. If it is to be used at the same time as another vaccine, it should be administered at separate injection sites and preferably on different limbs. It should be noted that the adverse reactions may be intensified.

Pregnancy

Inactivated influenza vaccines, such as Cell-based Trivalent Influenza Vaccine Seqirus, 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 a prospective pregancy exposure registry in 665 women vaccinated with Cell-based Quadrivalent Influenza Vaccine Seqirus during all stages of pregnancy, and worldwide use of influenza vaccines do not indicate any adverse foetal, newborn, pregnancy and maternal outcomes attributable to the vaccine.

Reproductive and developmental toxicology data do not predict an increased risk of developmental abnormalities.

Breast-feeding

It is unknown whether the vaccine is excreted in human milk. No effects on breast fed newborn/infant are anticipated. Cell-based Trivalent Influenza Vaccine Seqirus may be given during lactation.

Fertility

No human fertility data are available. Animal data have not shown effects on female fertility. Male fertility has not been assessed in animals.

Cell-based Trivalent Influenza Vaccine Seqirus has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

Data for Cell-based Quadrivalent Influenza Vaccine Seqirus are relevant to Cell-based Trivalent Influenza Vaccine Seqirus because both vaccines are manufactured using the same process and have overlapping compositions.

Adults 18 years and older

In a randomised clinical trial, safety was evaluated in 1 334 adults who received Cell-based Quadrivalent Influenza Vaccine Seqirus and 1 346 adults who received Cell-based Trivalent Influenza Vaccine Seqirus formulations.

The most commonly reported (≥10%) reactions in adult subjects were pain at the injection site (34%), headache (14%), fatigue (16%), myalgia (12%), injection site erythema (13%) and injection site 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 surveillance.

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 (6 months to less than 18 years of age)

The safety of Cell-based Quadrivalent and Trivalent Influenza Vaccines Seqirus has been evaluated in four randomised clinical trials. In these trials, 5 221 subjects 6 months to less than 6 years of age and 2 649 subjects 6 years to less than 18 years of age received Cell-based Quadrivalent Influenza Vaccine Seqirus; 1 173 children 4 years to less than 18 years received Cell-based Trivalent Influenza Vaccine Seqirus.

The most common (≥10%) local and systemic adverse reactions after any vaccination in children 6 months to less than 6 years of age were tenderness at the injection site (54%), irritability (28%), sleepiness (27%), injection site erythema (26%), injection site induration (22%), diarrhoea (18%), change in eating habits (17%), injection site ecchymosis (12%) and fever (11%).

The most common (≥10%) local and systemic adverse reactions after any vaccination in children 6 years to less than 18 years of age were pain at the injection site (69%), injection site erythema (26%), headache (23%), injection site induration (22%), fatigue (19%), myalgia (18%), injection site ecchymosis (11%) and loss of appetite (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 vaccine dose the incidence of adverse reactions following the second dose was similar or slightly lower to that observed after the first dose.

The highest frequency of adverse reactions in children 6 months to less than 18 years of age in paediatric clinical studies are described in Table 2 below.

Table 2: Solicited adverse reactions reported in clinical studies in children 6 months to < 18 years of age

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

There are no data for overdose with Cell-based Trivalent Influenza Vaccine Seqirus.

Pharmacotherapeutic group: Influenza vaccine, ATC code: J07BB02

Mechanism of action

Cell-based Trivalent Influenza Vaccine Seqirus provides active immunisation against the influenza virus strains contained in the vaccine. It induces humoral antibodies against the haemagglutinins. These antibodies neutralise influenza viruses.

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

Data for Cell-based Quadrivalent Influenza Vaccine Seqirus are relevant to Cell-based Trivalent Influenza Vaccine Seqirus because both vaccines are manufactured using the same process and have overlapping compositions.

Adult population

Clinical efficacy of cell-based trivalent influenza vaccine (TIVc) against culture-confirmed influenza in adults

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 = 3 828), an egg-based comparator vaccine (N = 3 676) or placebo (N = 3 900) 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)

^* 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.

Immunogenicity of Cell-based Quadrivalent and Trivalent Influenza Vaccines Seqirus in adults

In a randomised, double‑blind, controlled study (V130_01), adult subjects received Cell-based Quadrivalent Influenza Vaccine Seqirus (N = 1 334) or one of two trivalent formulations (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.

Cell-based Quadrivalent Influenza Vaccine Seqirus was shown to be non-inferior to TIVc, including in age subgroup analyses (subjects 18 to less than 65 years of age and 65 years of age and above) (see Table 4).

Table 4: Immunogenicity of Cell-based Quadrivalent and Trivalent Influenza Vaccines Seqirus in adults 18 years of age and above – Per protocol analysis set (V130_01)

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.

Paediatric population

Clinical efficacy of Cell-based Quadrivalent Influenza Vaccine Seqirus in the paediatric population 6 months to less than 18 years of age

Absolute efficacy of Cell-based Quadrivalent Influenza Vaccine Seqirus was evaluated in children 2 years to less than 18 years of age in Study V130_12 and in children 6 months to less than 48 months, in Study V130_14.

Study V130_12 was a multinational, randomised, non-influenza vaccine comparator-controlled efficacy study conducted in 8 countries over 3 influenza seasons, in which 4 514 subjects were enrolled to received 0.5 ml of Cell-based Quadrivalent Influenza Vaccine Seqirus 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.

Vaccine 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 5).

Table 5: Absolute vaccine efficacy (95% CI) in subjects 2 years to less than 18 years of age – FAS Efficacy¹ (Study V130_12)

In Study V130_14, absolute efficacy of Cell-based Quadrivalent Influenza Vaccine Seqirus was evaluated in children 6 months to less than 48 months of age. This was a multicentre, randomised, observer-blind, non-influenza vaccine comparator-controlled efficacy study conducted in 15 countries over 5 influenza seasons. In the study, 5 697 subjects received either Cell-based Quadrivalent Influenza Vaccine Seqirus (N=2 857) or a non-influenza vaccine comparator (N=2 840) in a 1:1 ratio. The full analysis set (FAS) for efficacy consisted of 5691 subjects. Based on influenza vaccination history, participants received one or two doses (28 days apart) of the study vaccine.

Vaccine 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 real-time polymerase chain reaction (RT‑PCR) and viral culture. An ILI episode was defined as a fever body temperature ≥ 37.8°C with at least one of the following on the same day: cough, sore throat, nasal congestion, rhinorrhoea, earache or ear discharge. Vaccine efficacy against laboratory confirmed influenza was calculated (Table 6).

Table 6: Absolute vaccine efficacy (95% CI) in subjects 6 months to less than 4 years of age – FAS Efficacy¹ (Study V130_14)

Immunogenicity of Cell-based Quadrivalent Influenza Vaccine Seqirus in children 6 months to less than 4 years of age

In a randomised, observer-blind, multicentre study (Study V130_10), 1597 subjects received Cell-based Quadrivalent Influenza Vaccine Seqirus and 805 subjects received a comparator quadrivalent influenza vaccine. The immune response to each of the vaccine antigens was assessed, 28 days after last vaccination. The immunogenicity endpoints were geometric mean antibody titres (GMTs) and percentage of subjects who achieved seroconversion, defined as a pre-vaccination HI or MN titre of <1:10 with a post-vaccination titre ≥1:40 or with a pre-vaccination HI or MN titre ≥ 1:10 and a minimum 4‑fold increase in serum antibody titre. GMTs and seroconversion rates were measured by haemagglutination inhibition (HI) assay for A/H1N1, B/Yamagata and B/Victoria strains and by microneutralization (MN) assay for the A/H3N2 strain.

Cell-based Quadrivalent Influenza Vaccine Seqirus was noninferior to the comparator QIV for all 4 influenza strains (see Table 7).

Table 7: Noninferiority of Cell-based Quadrivalent Influenza Vaccine Seqirus relative to comparator QIV in children 6 months to less than 4 years of age – Per-Protocol Analysis Set (V130_10)

Abbreviations: GMT = Geometric Mean Titre. CI = Confidence Interval.

^a Seroconversion rate = percentage of subjects with either a pre-vaccination titre < 1:10 and post-vaccination titre ≥ 1:40 or with a pre-vaccination titre ≥ 1:10 and a minimum 4-fold increase in post-vaccination antibody titre

Bold = Non-inferiority criterion met

Not applicable.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity and toxicity to reproduction and development.

Sodium chloride

Potassium chloride

Magnesium chloride hexahydrate

Disodium phosphate dihydrate

Potassium dihydrogen phosphate

Water for injections

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

12 months

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.

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.

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.