NONCLINICAL REGULATORY CONSIDERATIONS FOR WOUND-HEALING GROWTH-FACTORS

Initial evaluation of the safety of wound‐healing growth factors, whether manufactured by biotechnology or not, is dictated by the extent of knowledge of the physiologic, pharmacologic, and toxicologic effects, in vitro and in vivo in animals, and in man at the proposed dose and duration of administration. Prior to Phase 1 clinical study, products are studied to establish evidence of pharmacologic activity, understand the mechanism of action, evaluate the potential human risk, and establish a clinical study dose range. It is difficult to establish a generic plan and generic protocols for the preclinical development of wound‐healing growth factors because the toxicologic concerns and suggested studies are tailored to the uniqueness of each product. The quantity of useful information which can be gained from preclinical studies is considered for each product on a case‐by‐case basis, taking into account the availability of a relevant model. Preliminary information regarding (1) production of the active moiety, (2) ingredients in the final formulation as it is to be marketed, (3) characterization of the growth factor, (4) the proposed dose and route of administration, (5) the known actions and effects, (6) the similarity to the endogenous growth factors, and (7) the proposed target clinical study population is needed to determine the most appropriate preclinical pharmacological and toxicologic studies. Use of this information and additional data relating the pharmacokinetic and toxicologic profiles will be discussed with respect to generalizations in study concepts for pharmacology and toxicology studies and individualization of these preclinical studies which may occur, based upon the uniqueness of the compound. Copyright © 1990 Wiley‐Liss, Inc.