A review of the changes to the licensing of influenza vaccines in Europe

Abstract

In 2014, the European Committee for Medicinal Products for Human Use (CHMP) published a draft regulatory guideline for the evaluation of influenza vaccines. Following a public consultation round, the final guidance will be published in the near future. Here, we highlight the main changes in the clinical section in this guideline and discuss the background to these changes and whether the new consolidated guidance document can be expected to achieve a better understanding of the performance of seasonal, zoonotic and pandemic influenza vaccines during the regulatory licensing process. The new influenza guideline reflects a changed approach to the regulatory assessment of influenza vaccines, resulting in the abolition of serological criteria, known as the CHMP criteria, which have been the mainstay for evaluating the influenza vaccine immunogenicity for several decades. The new guideline adopts a more diversified approach to the measurement and reporting of the immune response to influenza vaccines and sets a requirement to conduct clinical outcome trials in young children. Importantly, more emphasis is placed on the post‐licensure monitoring of the benefit risk of influenza vaccines, including a request for continuous monitoring of efficacy and enhanced safety surveillance. Despite the improvements these new requirements will expectedly bring to the regulatory assessment of influenza vaccines, major challenges remain which cannot be overcome by new guidance alone. Ongoing initiatives in which academia, manufacturers, public health institutes and regulators work together to address these challenges are central to the development of robust tools to evaluate and monitor performance of influenza vaccines in the future.

Single radial haemolysis compared to haemagglutinin inhibition and microneutralization as a correlate of protection against influenza A H3N2 in children and adolescents

“…Currently, there are no established correlates of protection for young age groups in all the three assays. Nevertheless, the new CHMP guideline has abolished the traditional criteria with the recognition that relying on these criteria of measuring protective effectiveness might not be appropriate for various situations and this opens the opportunities to advance the field on correlates of protection in various subpopulations against different influenza strains …”

“…Nevertheless, the new CHMP guideline has abolished the traditional criteria with the recognition that relying on these criteria of measuring protective effectiveness might not be appropriate for various situations and this opens the opportunities to advance the field on correlates of protection in various subpopulations against different influenza strains. 9 Another key finding was that SRH appears to have the worst correlation with protection against influenza H3N2, as the estimates of protective efficacy fluctuated when the cut-off SRH values increased.…”

“…These thresholds however were derived from limited challenge studies in healthy adults performed decades ago and the transferability of these thresholds to other subpopulations, such as children, has never been established. In recent years, there has been growing recognition of the limitation of these established criteria which has led to the abolition of these criteria in the newly developed guideline for influenza vaccine licensing effective February 2017 by CHMP . Until now, there has still been a relative lack of data on all three aforementioned serologic assays as correlates of protection against influenza in young age groups.…”

“…In recent years, there has been growing recognition of the limitation of these established criteria which has led to the abolition of these criteria in the newly developed guideline for influenza vaccine licensing effective February 2017 by CHMP. 8,9 Until now, there has still been a relative lack of data on all three aforementioned serologic assays as correlates of protection against influenza in young age groups.…”

Oil-in-water emulsion adjuvants for pediatric influenza vaccines: a systematic review and meta-analysis

“…Mouse experiments showed that MF59 stimulates the local inflammatory response at the injection site and thus increases the uptake of antigen by activated dendritic cells 43 . Similarly, AS03 facilities a stronger antibody response by inducing a local cytokine and chemokine response at the injection site to enhance antigen uptake 43 .…”