Preclinical and pharmacology and toxicology of hematopoietic growth factors.
Initial evaluation of the safety of biological products, whether manufactured by biotechnology or not, is dictated by the extent of knowledge of the biological effects in vitro, in animals, and in man at the proposed dose and duration of administration. The quantity of useful information that will be gained from an animal study is considered for each product on a case-by-case basis. This requires consideration of the availability of a relevant species. Relevance is determined by presence and relative affinity and distribution of receptors for the biological product, relative potency in induction of biological activity related to the putative mechanism of action and pharmacokinetic considerations. The impurities and immunogenic potential of the product are also considered in designing the preclinical studies. After evaluating all these factors, the residual lack of knowledge is FDA's basis for recommending specific preclinical testing. The considerations inherent in the preclinical evaluation of factors acting primarily on hematopoietic cells, erythropoietin (EPO), interleukins (IL's) and colony stimulating factors (CSF) (1) will be discussed using case examples.
Weissinger
J
J
HFD-502, Center for Drug Evaluation and Research, FDA, Rockville, MD 20857, USA.