Pharmaceutical toxicology

This chapter aims to highlight the core principles of pharmaceutical toxicology. It is an interrelated discipline that needs to be applied at all stages of the drug development process to appropriately characterise the safety profile of a drug compound and acknowledge the uncertainties associated with models available. With a strategic mindset, the preclinical safety activities aim to build a comprehensive profile of the drug so that potential hazards can be identified and the risks for healthy trial subjects or patients quantified, and, if necessary, suitable means for eliminating or reducing unacceptable risks can be put in place. We focus on the 2 distinct phases of pharmaceutical toxicology: Discovery toxicology and regulatory toxicology, to explain how the thinking is built upon at each stage and how the mindset shifts from enabling the selection of an optimally derisked clinical candidate through to thorough risk characterisation and management of those risks for clinical development. Considering attrition due to safety reasons, whether clinical or preclinical, is one of the main reasons for drug project failure, safety assessments should be viewed with equal importance as drug efficacy assessments.