An overview of the regulation of influenza vaccines in the United States

Abstract

Influenza virus vaccines are unique among currently licensed viral vaccines. The vaccines designed to protect against seasonal influenza illness must be updated periodically in an effort to match the vaccine strain with currently circulating viruses, and the vaccine manufacturing timeline includes multiple, overlapping processes with a very limited amount of flexibility. In the United States (U.S.), over 150 million doses of seasonal trivalent and quadrivalent vaccine are produced annually, a mammoth effort, particularly in the context of a vaccine with components that usually change on a yearly basis. In addition, emergence of an influenza virus containing an HA subtype that has not recently circulated in humans is an ever present possibility. Recently, pandemic influenza vaccines have been licensed, and the pathways for licensure of pandemic vaccines and subsequent strain updating have been defined. Thus, there are formidable challenges for the regulation of currently licensed influenza vaccines, as well as for the regulation of influenza vaccines under development. This review describes the process of licensing influenza vaccines in the U.S., the process and steps involved in the annual updating of seasonal influenza vaccines, and some recent experiences and regulatory challenges faced in development and evaluation of novel influenza vaccines.

Keywords: influenza vaccines; vaccine licensing; vaccine regulation.

Figure 1

Timelines of influenza vaccine production. The various activities associated with the annual production of influenza vaccine in the Northern Hemisphere are listed and the approximate times during the year when they take place are shown. For comparison, the timing of these activities during the 2009 H1N1 pandemic is overlaid in blue.

Figure 2

Licensing of pandemic influenza vaccines. A schematic diagram for licensing of pandemic influenza vaccines. The effectiveness of a pandemic influenza vaccine is inferred from the demonstrated efficacy of a licensed seasonal vaccine made by the same manufacturing process and supported by clinical studies supporting the safety and immunogenicity of the pandemic vaccine. During a pandemic, the license can be updated with a strain change of the same HA subtype in a process similar to that used for updating seasonal vaccines.