Challenges in the development of egg-independent vaccines for influenza.

Introduction: Current influenza vaccines are mainly produced from viruses propagated in eggs, an established process developed over 70 years. However, this technology presents some drawbacks and other platforms are under development or have been already developed in order to replace or to be used alongside the old one. Area covered: The present review provides an overview of influenza vaccine production, starting from egg-based technology, to cell-derived vaccines, until the novel platforms/technologies for the production of influenza vaccines such as DNA-based vaccines, virus-like particles and plant-based technology. Expert opinion: The ideal method of production should have certain characteristics such as great flexibility and scalability, the viruses should be representative of the circulating strains, process should be standardized and controlled, and it should be possible to start production as soon as the sequence of the new influenza strain is available. However, it is important not to underestimate the fact that some parts of the vaccine production process have been established for egg-based vaccines. Thus, changes in vaccine production methods are not merely 'technical changes'; rather, they involve various aspects that slow down the authorization of new influenza vaccines and make the complete replacement of egg-based production unlikely in the near future.