Informal consultation on the WHO recommendations for the production and control of influenza vaccines (human, live attenuated), 26-27 February 2009, WHO HQ Geneva
Summary and meeting documents
Viral influenza causes significant human morbidity and mortality requiring costly medical and public health interventions during epidemics. Excess mortality often accompanies influenza epidemics, mostly in the elderly; however, they more often originate in immunologically susceptible individuals capable of rapidly spreading the infection through a community, notably school age children. An effective measure of viral influenza prophylaxis generally available is vaccination. Live attenuated influenza vaccines based on "cold adapted" donor strains administered intra-nasally have been used to control influenza infection and illness since last century. Despite more than 50 years of successful public health experience with live attenuated influenza vaccines in the Russian Federation, and, more recently, in the United States of America, these vaccines currently represent less than 1% of global influenza vaccine production.
The advantages of live attenuated influenza vaccines include:
- simplicity of intranasal administration
- increased indirect protection through herd immunity via vaccination of children
- simpler downstream process than inactivated vaccines making them more appropriate for technology transfer to developing countries
- lower unit cost with production yield 10 times higher than inactivated vaccines
- 10 times lower capital investment required for an egg-based live vaccine production (US$10 millions) in an already established vaccine manufacturing plant to what is required for egg-based inactivated vaccines (US$100-200 millions)
- significantly higher investment would be required for the establishment and regulatory approval of a cell culture-based influenza vaccine producing facility.
The continuing commercial development and public health use of live attenuated influenza vaccines made it appropriate to review and update the WHO recommendations which currently date from 1978. In the intervening years, significant technical and scientific advancement in influenza vaccine production has been made. Considerable effort has also been directed to pandemic preparedness to ensure that safe and effective vaccines can quickly be produced in response to a public health emergency. Consequently, it is necessary to update the WHO recommendations for the production and control of influenza vaccines (human, live attenuated) to reflect new developments and current practices in the field.
The WHO recommendations are intended to provide vaccine manufacturers and national regulatory authorities (NRA) with up to date guidance on the development of specific processes for production and control of, and the non-clinical and clinical evaluation of influenza vaccines (human, live attenuated). The meeting objective was to review, discuss and agree on the input from stakeholders in national immunization programs, basic research and public health sciences, regulatory authorities, and vaccine manufacturing on the proposed draft document. The aim was to enable the production of up-to-date "WHO recommendations for the production and control of influenza vaccines (human, live attenuated)" to be submitted for endorsement by the Expert Committee on Biological Standardization (ECBS). The objective of reviewing the entire document was accomplished on time. The general consensus was that a new draft addressing all input from this consultation would provide evidence based- state-of-the art recommendations on quality, safety, and efficacy of human influenza vaccines (live attenuated) that can be submitted for review to ECBS in October 2009.