Difficulties in conceiving and applying guidelines for the safety evaluation of biotechnologically-produced drugs:...

Pharmaceutical companies and regulatory authorities need guidelines for the safety evaluation of all drugs. Nevertheless, new types of drugs, e.g. biological products produced by novel biotechnological processes (as recombinant DNA methods), induce new problems for this evaluation. The following points will be assessed: (1) As a postulate, safety is highly dependent on the industrial process and on the controls. (2) To conceive guidelines, it is necessary to take into account the structure of the pharmaceutical product compared with the natural biological product (identical or not), the therapeutical use and the relevance of the classical toxicological investigations: for example single dose toxicity gives poor results for target organs, repeated dose toxicity is related to immunogenicity, mutagenicity testing is debatable. (3) To apply guidelines is still more difficult, for example to select animal models (animal models of diseases), define dose levels, evaluate immunogenicity, conceive the design of reproduction studies and the feasibility of cancerogenicity studies. Therefore, common sense and a case-by-case approach are necessary (guidance vs. guidelines) for the safety evaluation of drugs produced by biotechnology, and an early collaboration between all the partners (companies, experts and regulatory authorities).