Safety evaluation of biological and biotechnology-derived medicines.

Evaluating the 'safety' of drugs produced by biotechnology resembles the assessment of conventional 'new chemical entities,' but with certain major differences. The 'quality' of the product requires careful control because of concern about the carry-over of DNA, immunogenic proteins, endotoxin and process chemicals. Equally the potency and purity of the product must also be considered, as well as its identity. The toxicity testing of rDNA-derived proteins, monoclonal antibodies and vaccines, although increasingly being swept under the umbrella of conventional studies, should be empirically devised according to the nature and physiological effects of the substance, taking account of the responsiveness of suitable species for non-clinical testing, the potential immunogenicity of heterologous proteins and any effect the drug may have on physiological mechanisms and the immune status of the test animals. Conventional types of single and multidose and reproduction toxicity experiments can then be adapted to detect and investigate any hazard of the novel drug. Kinetics, metabolism and drug interactions should be explored and the regulatory demand for genotoxicity data satisfied. If appropriate, immunological actions, including auto-immunity, can be sought. 'Safety-in-use' should then be predictable with some confidence, because of the extent of the toxicological investigations and because activities that cannot be examined will have been delineated, e.g. lack of a responsive species or of a suitable laboratory procedure.