Design and Writing of the Preclinical Safety Report

Assessment of the preclinical safety of a new chemical entity or biotechnology-derived drug is based on the results of a series of in sitro and in vivo studies designed to demonstrate the potential toxicity of a compound. The reports that document the results of these studies become part of larger documents (IND/NDA/HRD) that incorporate all of the preclinical safety reports and summarize, and ultimately characterize, the preclinical safety of a compound. To aid this process requires that the report for each study be complete, conservatively interpreted, and clearly written. Preparation of the individual toxicology report provides the writer(s) with the vehicle with which to communicate his/her/their interpretations of the results of the study. However, the writer(s) of the individual report must realize that the safety assessment for a compound is based on the results of a series of studies conducted in both rodent and nonrodent species and is not based on the results of a single study. The assessment is based on the results of studies that vary in length from those using a single high dose to studies that include daily dosing in carcinogenicity studies for 24 mo. These studies are complimented by in vitro and iii vivo genetic toxicity studies and a series of reproduction studies that evaluate effects on reproductive performance of both male and female, potential teratogenicity in the offspring and effects on parturition and the postpartum development of the offspring.