SAFETY EVALUATION OF BIOLOGICAL AND BIOTECHNOLOGY-DERIVED MEDICINES

Evaluating the 'safety' of drugs produced by biotechnology resembles t he assessment of conventional 'new chemical entities,' but with certai n major differences. The 'quality' of the product requires careful con trol because of concern about the carry-over of DNA, immunogenic prote ins, endotoxin and process chemicals. Equally the potency and purity o f the product must also be considered, as well as its identity. The to xicity testing of rDNA-derived proteins, monoclonal antibodies and vac cines, although increasingly being swept under the umbrella of convent ional studies, should be empirically devised according to the nature a nd physiological effects of the substance, taking account of the respo nsiveness of suitable species for non-clinical testing, the potential immunogenicity of heterologous proteins and any effect the drug may ha ve on physiological mechanisms and the immune status of the test anima ls. Conventional types of single and multidose and reproduction toxici ty experiments can then be adapted to detect and investigate any hazar d 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 confid ence, because of the extent of the toxicological investigations and be cause activities that cannot be examined will have been delineated, e. g. lack of a responsive species or of a suitable laboratory procedure.