Regulatory Decision Summary for Flucelvax

Since 2020, no naturally occurring B/Yamagata lineage viruses have been detected. As a result, the world health organization (WHO) has decided not to include the B/Yamagata strain in the composition of the 2024–2025 influenza vaccine. In compliance with this recommendation, Seqirus plans to transition from Flucelvax quadrivalent cell-based vaccine (QIVc) to Flucelvax trivalent cell-based vaccine(TIVc). The clinical development program supporting the registration of QIVc was built upon that of TIVc. The TIVc drug product is equivalent in composition to QIVc, with a comparable formulation and filling process, except for the absence of the second B antigen.

The purpose of this New Drug Submission (NDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Flucelvax filed by Seqirus UK Limited to support the use of cell-derived trivalent influenza vaccine (TIVc) for persons aged 6 months and older based on the evidence from the clinical development of TIVc and QIVc.

Vaccination against infectious diseases remains one of the most effective public health strategies. Influenza poses a particular threat to the elderly and young children, especially those under two years old. While the protective benefits of vaccinating children are well-established, any potential risks must be carefully balanced against these advantages.

Unlike traditional influenza vaccines, which are typically produced using embryonated chicken eggs, TIVc and QIVc are developed using mammalian cell lines. Egg-based production can lead to antigenic changes due to mutations, potentially reducing vaccine effectiveness. However, cell-based manufacturing and cell-derived candidate vaccine viruses (CVVs) eliminate this issue.
 

Flucelvax Quad has been authorized for marketing in Canada since 2019.
 

Both QIVc and TIVc are considered to have favorable benefit-risk profiles for individuals six months and older, owing to their shared production methods and similar components. Clinical data suggest that the benefit-risk profile of TIVc is comparable to that of QIVc, supporting its use in influenza prevention for this age group.
 

The clinical development programs for the trivalent (TIVc) cell-based influenza vaccines have yielded key findings.

• Effectiveness: TIVc showed 83.8% effectiveness against vaccine-like influenza strains and 69.5% against all culture-confirmed strains in adults aged 18 to under 50.

• Immunogenicity: TIVc's immune response was non-inferior to egg-based vaccines (TIVe) in people aged 18 and older.

• Children’s Response: In children aged 4 to under 9, TIVc and TIVe elicited strong antibody responses, comparable to those seen in older children and adults.

• Comparative Immunogenicity: Studies showed TIVc's immune response was comparable to licensed egg-based vaccines for individuals aged 4 and older.

• Immune Persistence: Long-lasting immune responses were confirmed in follow-up studies.

The overall data support the use of Flucelvax across various age groups, emphasizing their effectiveness, safety, and robust immune responses.
 

The Risk Management Plan (RMP) for Flucelvax (Influenza Vaccine [surface antigen, inactivated, prepared in cell cultures]) was submitted to Health Canada as part of a New Drug Submission. The RMP is designed to describe known and potential safety issues, to present the monitoring plan and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP is considered to be acceptable and identified appropriate monitoring (pharmacovigilance) activities and risk minimization measures for Flucelvax. This included providing information in the product monograph and identifying populations and areas where more data are needed. The safety of Flucelvax will continue to be evaluated through periodic safety reports.
 

An updated Risk Management Plan (RMP) for Flucelvax was reviewed by Health Canada and considered acceptable.
 

Risks have been communicated in the approved Product Monograph and will continue to be monitored post market as outlined in the Risk Management Plan, with routine and non-routine pharmacovigilance activities.
 

The chemistry and manufacturing information submitted for Flucelvax has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.
 

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.
 

Overall, the benefit-harm-uncertainty profile was favourable for Flucelvax 15 mcg/strain/0.5mL for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.
 

For further details about Flucelvax, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.