Delivery of a vaccine in a programme such as Expanded Program on Immunization is the end result of years of discovery and development. Only a tiny percentage of candidate vaccines progress to licensing, making the costs of vaccine Research and Development extremely high. This fact also makes it essential to maintain a healthy product portfolio, with a range of vaccines at different stages in the pipeline.
Development of vaccines can be simplified into two broad stages:
- Pre-clinical development is research carried out in lab assays and on animals. It includes:
- Identification (discovery) of relevant antigens (e.g. screening)
- Creation of the vaccine concept
- Evaluation of vaccine efficacy in test tubes and animals
- Manufacture of the vaccine to Good Manufacturing Practice standards
- Clinical development is when the vaccine is first tested in humans. It covers four stages over several years, from initial clinical trials in humans (phase I) right through to introduction and beyond (phase IV). Clinical development is built on rigorous ethical principles of informed consent from volunteers, with an emphasis on vaccine safety as well as efficacy.
Phase I clinical trials are small-scale trials to assess whether the vaccine is safe in humans and what immune response it evokes. For diseases of poverty this covers trials in European volunteers (phase Ia) and then in populations in Developing Countries (phase Ib).
Phase II clinical trials are larger and look mainly to assess the efficacy of the vaccine against artificial infection and clinical disease. Vaccine safety, side-effects and the immune response are also studied.
Vaccines that progress to phase III clinical trials are studied on a large scale of many hundreds of subjects across several sites to evaluate efficacy under natural disease conditions. If the vaccine retains safety and efficacy over a defined period, the manufacturer is able to apply to the regulatory authorities for a licence to market the product for human use.
The finalhase IV happens after the vaccine has been licensed and introduced into use. Also called post-marketing surveillance, this stage aims to detect rare adverse effects as well as to assess long term efficacy.