Advanced search

Report side effect

Report a suspected side effect or falsified product to the MHRA Yellow Card scheme.
Go to {yellow_card_logo} site
{arrow_up} Back to top

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe {equilateral_black_triangle}

Active Ingredient:
influenza vaccine (surface antigen, inactivated)
Company:  
Seqirus UK Limited See contact details
ATC code: 
J07BB02
{info_black}
About Medicine
{healthcare_pro_orange} This information is for use by healthcare professionals
Last updated on emc: 30 Oct 2023

black_triangle.svg 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

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

Influenza vaccine, prepared in cell cultures

2. Qualitative and quantitative composition

Influenza virus surface antigens (haemagglutinin and neuraminidase), inactivated, of the following strains*:

A/Wisconsin/67/2022 (H1N1)pdm09-like strain (A/Georgia/12/2022 CVR-167) 15 micrograms HA**

A/Darwin/6/2021 (H3N2)-like strain (A/Darwin/11/2021, wild type) 15 micrograms HA**

B/Austria/1359417/2021-like strain (B/Singapore/WUH4618/2021, 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 2023/2024 season.

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 6 months of age.

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe should be used in accordance with official recommendations.

4.2 Posology and method of administration

Posology

Adults and children from 6 months of age:

Age Group

Dose

Schedule

6 months 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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.

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 febrile illness until the fever is resolved.

As with all injectable vaccines, Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe. Concomitant administration of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe with other vaccines has not been studied in trials conducted by Seqirus. Based on clinical experience with cell-based trivalent influenza vaccine (TIVc), Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe can be given at the same time as other vaccines. If Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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.

Data assessed by the MHRA that support concomitant administration of influenza vaccines with COVID-19 vaccines (but at separate injection sites) are based on the ComFluCOV study [EudraCT Number: 2021-001124-18], which investigated concomitant administration in adults of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe with COVID-19 mRNA Vaccine BNT162b2 (Pfizer/BioNTech) and COVID-19 Vaccine AstraZeneca. The data show that the antibody responses are unaffected and that the reactogenicity profile is acceptable.

4.6 Fertility, pregnancy and lactation

Pregnancy

Inactivated influenza vaccines, such as Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe, 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe. 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe is excreted in human milk. No effects on breast fed newborn/infant are anticipated. Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe in adults 18 years and older was evaluated in a randomised, controlled study (V130_01), in which 1334 subjects received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe. Similar rates of solicited local and systemic adverse reactions were reported in subjects who received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe and cell-based trivalent influenza vaccine comparator in this clinical trial.

The most commonly reported (≥ 10%) reactions in subjects who received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe were pain at the injection site (34%), headache (14%), fatigue (14%), 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.

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,

Guillain-Barre Syndrome

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,

Injection site erythema, Injection site induration1

Injection site 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 (6 months to less than 18 years of age)

The safety of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe in children 6 months to less than 18 years of age has been evaluated in three clinical studies, V130_03, V130_12 and V130_10. In these studies, 2365 subjects 6 months to less than 6 years of age, 953 subjects 6 to less than 9 years of age, and 1696 subjects 9 to less than 18 years of age received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe. Children less than 9 years of age received either one or two doses (separated by 28 days) based on their previous influenza vaccination history and all children 9 to less than 18 years of age received one dose. Among subjects 6 months to less than 6 years of age, 1083 received one dose and 1282 received two doses. Among children 6 to less than 9 years of age, 338 received one dose and 615 received two doses.

The most common local and systemic adverse reactions reported across the three studies are described by paediatric sub-group with the highest percentage reported from any of the three studies shown in Table 2 below.

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%), injection site erythema (19%), fatigue (18%), myalgia (16%), and injection site 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%), myalgia (15%), injection site ecchymosis (11%) and loss of appetite (11%).

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%), diarrhoea (18%), injection site induration (17%), change in eating habits (17%) 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe the incidence of adverse reactions following the second dose of vaccine was similar or slightly lower to that observed with the first dose.

The highest frequency of adverse reactions in children 6 months to less than 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 6 months to < 18 years of age

MedDRA System Organ class

Adverse Reactions

Frequency

6 months to < 6 years

6 to <9 years

9 to < 18 years

Metabolism and nutrition disorders

Loss of appetite

N/A

Very common

Common

Change in eating habits

Very common

N/A

N/A

Nervous system disorders

Headache

N/A

Very common

Very common

Gastrointestinal disorders

Diarrhoea

Very Common

Common

Common

Nausea

N/A

Common

Common

Vomiting

Common

Common

Common

Musculoskeletal and connective tissue disorders

Myalgia

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

Chills/Shivering

Common

Common

Common

Fever (≥ 38° C)

Common

Common

Common

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.

4.9 Overdose

There are no data for overdose with Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Influenza vaccine, ATC code: J07BB02

Mechanism of action

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe provides active immunisation against four influenza virus strains (two A subtypes and two B types) contained in the vaccine. Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe induces humoral antibodies against the haemagglutinins. These antibodies neutralise influenza viruses.

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe in Adults 18 years of age and older

Immunogenicity of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe was evaluated in adults 18 years of age and older in a randomised, double-blind, controlled study (V130_01). In this study, subjects received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe (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.

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe was non-inferior to TIVc. Non-inferiority was established for all 4 influenza strains included in Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe, 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe relative to TIVc in adults 18 years of age and above – Per protocol analysis set (V130_01)

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

N = 1250

TIV1c/TIV2ca

N = 635/N = 639

Vaccine Group Ratio

(95% CI)

Vaccine Group Difference

(95% CI)

A/H1N1

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/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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe in Children and Adolescents 6 months to less than 18 Years of Age

Immunogenicity of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe in the paediatric population was evaluated in 2 clinical studies, V130_03 and V130_10.

Immunogenicity of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe (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.

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe, 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe or TIV1c/TIV2c - Per Protocol Set (V130_03)

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

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%.

Immunogenicity of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe was evaluated in children 6 months to less than 4 years of age in a randomised, observer-blind, multicentre study conducted in the US (Study V130_10). In this study, subjects received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe or a comparator quadrivalent influenza vaccine (Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe N=1597, Comparator QIV N=805). In the per protocol set, the mean age of subjects who received Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe was 29 months. 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 (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe was noninferior to the Comparator QIV. Noninferiority was established for all 4 influenza strains as assessed by ratios of GMTs and the differences in the percentages of subjects achieving seroconversion at 4 weeks following vaccination (see Table 6).

Table 6: Noninferiority of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe Relative to Comparator QIV in Children 6 Months to Less Than 4 Years of Age – Per-Protocol Analysis Set (V130_10)

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

Comparator QIV

Vaccine Group Ratio

Vaccine Group Difference

A/H1N1

N = 1092

N =575

GMT (95% CI)

78.0

(70.8, 86.0)

57.3

(50.8, 64.6)

0.73

(0.65, 0.84)

-

Seroconversion Rate a (95% CI)

58.2%

(55.3, 61.2)

46.8%

(42.6, 51.0)

-

-11.5

(-16.5, -6.4)

A/H3N2

N = 1078

N = 572

GMT (95% CI)

23.1

(21.2, 25.1)

23.9

(21.6, 26.6)

1.04

(0.93, 1.16)

-

Seroconversion Rate a (95% CI)

27.6%

(25.0, 30.4)

30.8%

(27.0, 34.7)

-

3.1

(-1.4, 7.8)

B/Yamagata

N = 1092

N = 575

GMT (95% CI)

35.6

(32.9, 38.6)

26.0

(23.5, 28.6)

0.73

(0.66, 0.81)

-

Seroconversion Rate a (95% CI)

46.5%

(43.5, 49.5)

31.7%

(27.9, 35.6)

-

-14.9

(-19.6, -10.0)

B/Victoria

N = 1092

N = 575

GMT (95% CI)

22.4

(20.7, 24.2)

19.6

(17.8, 21.6)

0.88

(0.79, 0.97)

-

Seroconversion Rate a (95% CI)

30.3%

(27.6, 33.1)

24.4%

(20.9, 28.1)

-

-6.0

(-10.3, -1.4)

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

Assays: 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, using cell-derived target viruses.

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

Clinical efficacy of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe in the paediatric population 2 to less than 18 years of age

Absolute efficacy of Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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.

Cell-based Quadrivalent Influenza Vaccine (Surface Antigen, Inactivated) Seqirus suspension for injection in pre-filled syringe 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 7).

Table 7: 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

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

2257

175

7.8

54.63

45.67, 62.12

Non-Influenza Comparator

2252

364

16.2

-

-

Culture Confirmed Influenza

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

2257

115

5.1

60.81

51.30, 68.46

Non-Influenza Comparator

2252

279

12.4

-

-

Antigenically Matched Culture-Confirmed Influenza

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

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 particulars
6.1 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 UK Ltd.

Point, 29 Market Street,

Maidenhead SL6 8AA, UK

8. Marketing authorisation number(s)

PLGB 47991/0006

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 07/09/2021

10. Date of revision of the text

10/2023

Seqirus UK Limited
Company image
Address
The Point, 29 Market Street, Maidenhead, SL6 8AA, UK
Medical Information Direct Line
+44 (0) 1748 828816
Medical Information e-mail
[email protected]
Customer Care direct line
08457 451 500
Telephone
+44 (0)1628 641 500
Product Quality Complaints
[email protected]