Regulatory issues in the development of new vaccines with a special emphasis on safety aspects

Vaccines represent a major weapon against many infectious diseases. More recently, vaccines have demonstrated promising methods in the prevention or treatment of other types of disorders such as cancer and autoimmune diseases. Their composition has significantly evolved from the whole microorganism approach (attenuated or inactivated) to the use of crude fractions or purified parts of these organisms (polysaccharides and toxoids) through to protein-polysaccharide conjugates and now to recombinant proteins or polypeptides. Gene transfer products (naked DNA and vector-based vaccines), which are currently in pre-licensing phases, also represent a new approach in vaccinology [1]; they are already successfully used as veterinary vaccines for rabies or distemper. Therefore vaccines are multifaceted products and also act through a highly complex mechanism in which the antigen(s) by itself is not the final acting component of the immune response. Vaccines produce antibodies or activate T cells that are the actual effectors. Obviously, this complexity raises regulatory issues associated with the efficacy and safety assessment of vaccines. Vaccines fall within the scope of medicinal products (as defined by the amended Council Directive 65/65/EEC [2]) even if they are considered as a separate category as illustrated by the dedicated Office of Vaccines Research and Review within the U.S. Food and Drug Administration – Center for Biologics Evaluation and Research (FDA-CBER) organisation. Therefore they must undergo strict non-clinical and clinical safety evaluation before licensing in line with what is performed with drugs. This classification as a medicinal product associated with the specific status of vaccines implies that documents for pharmaceuticals in general and specific vaccine guidelines provide regulatory guidance for vaccine development. For instance, the WHO publishes appropriate vaccine guidelines covering the nonclinical and clinical development of vaccines only [3, 4]. One of the major differences between vaccines and other pharmaceuticals is the fact that they are given to healthy people, and predominantly to Regulatory issues in the development of new vaccines with a special emphasis on safety aspects