Safety evaluation of biotechnology products.

Preclinical safety studies with biotechnology products are not only performed for regulatory purposes, but should first and foremost provide information about the potential toxic effects in patients. The initial toxicological experience, using standard testing procedures developed for drugs of small molecular weight, often gave disappointing results, and the development of antibodies against the heterologous products cast doubt upon the validity of the testing approach. In order to assess the safety of new biotechnology products, compounds must be looked at on a case by case basis. Exaggerated pharmacodynamic effects are often responsible for the major toxicological problems. For some compounds, 'intrinsic toxicity', i.e. adverse effects due to the molecule per se, may play a role. With others, 'biological toxicity', i.e. the activation of physiological processes such as antigen-antibody interaction, release of mediators and cytokines, or initiation of the arachidonic acid-prostaglandin cascade, may be the cause of the observed adverse effects. Examples are given that show the importance of a good understanding of the biological mechanisms of action of toxicity observed in animals and in patients.