| Markus Wulf and Dr Peter Trinder of Thymed GmbH assess the clinical and preclinical development of vaccines, drugs and biotherapeutics
It is common knowledge in the biotechnology and pharmaceutical industries that the development of a new drug, vaccine or therapeutic entity is a long and expensive process. Following a candidate’s identification, it must be tested initially in the laboratory and then in animals. With a positive outcome, this is followed by clinical trials. In the case of vaccines, the typical development time is about 80 months, with a 17-25 per cent success rate (1), though for many pharmaceuticals development times are longer and the success rate significantly lower. Prior to a new drug, vaccine or therapeutic entering man, extensive testing in animals, often at very high doses, is required. Unfortunately, each species reacts differently; this is not therefore necessarily a guarantee that the new drug entity is safe for human use.
Although the immune systems of most mammals are very similar, they are not identical – above all, the immune system of an inbred laboratory mouse, primate or other animal, with a limited exposure to pathogens, is not the same as the typical human immune system that has been well primed by extensive exposure to a wealth of pathogens and other environmental factors (approximately 50 per cent of adult human T-cells are memory Tcells, present due to past infection or illness).
The regulatory authorities provide extensive guidelines to ensure that risks are minimised and safety maximised, and that these are updated where and when necessary. The US Food and Drug Administration (FDA) in its guidance for industry issued in 2002 (2), requires that for any new drug entity the potential for adverse effects on the immune system is assessed. Under the heading of ‘immunotoxicology’, the guidelines define five areas in which assessment should be made: adverse immunostimulation; autoimmunity; hypersensitivity/allergy; immunogenicity; and immunosuppression. |
