Phase III, randomized controlled trial to evaluate lot consistency of a trivalent subunit egg-based influenza vaccine...

Vaccination is the most effective preventive strategy to control influenza. The demonstration of lot-to-lot consistency to confirm the reliability of the manufacturing process has become a mandatory step in vaccine development. This phase III, observer-blind, controlled trial assessed lot-to-lot consistency, immunogenicity, and safety of a subunit trivalent influenza vaccine (Agrippal®, Novartis Vaccines and Diagnostics) in healthy adults aged 18-49 years. The immunogenicity and safety profile of Agrippal was compared with a control vaccine (Fluvirin®, Novartis Vaccines and Diagnostics). A total of 1507 subjects were randomized 2:2:2:1 to receive one vaccination of one of the three lots of influenza vaccine or control vaccine. Antibody levels were measured by hemagglutination inhibition assay on days 1 and 22. Adverse reactions were solicited via diary cards for 7 days after vaccination, and unsolicited adverse events were collected throughout the study period. Equivalence of day 22 immune responses to the three lots was shown for each of the three strains. Robust immunogenic responses after one dose were observed for all vaccine groups, and both Center for Biologics Evaluation and Research criteria for licensure of influenza vaccines were met for all three virus strains. Both vaccines exhibited a robust safety profile and were well tolerated, with no differences in local and systemic solicited reactions or in unsolicited adverse events. The demonstration of consistency between manufacturing lots confirms for purposes of clinical development the reliability of the production process. The robust immunogenic responses and favorable safety profiles further support the use of trivalent subunit influenza vaccines Agrippal and Fluvirin for active immunization against influenza.