Dose Range Finding (DRF) Studies in Drug Toxicology Assessments

Early repeated dose-range finding (DRF) toxicology studies, usually conducted in rodent and non-rodent animal species, seek to provide the earliest assessment of the toxicity profile of new chemical entities (NCE) using well-designed and validated nonclinical study designs. Thus, the DRF study provides the toxicologist with a means to expose any potential adverse effect liability of an NCE. The conduct of this study is critical as it provides important safety information to drug discovery research groups in their decision to develop or terminate costly development programs without sufficient safety margins. Establishment of the safety profile of a drug is a key responsibility in the conduct of DRF studies as it provides acute toxicological information on NCEs and an early overview of the toxicokinetic (TK) profile of the NCE following repeated dosing in rodents and non-rodent nonclinical species selected for use in the developing toxicology program. Any potential resolution for drug safety issues that arise in the early safety profiling of a compound requires the utilization of highly skilled drug safety scientists. These individuals have a broad understanding of essential toxicological principles and can distinguish adverse event development and subsequent mitigation and insight into clinical translational relevance.