Making Better Drugs: Decision Gates in Non-Clinical Drug Development: A guide to drug discovery

Key Points It is estimated that only 1 out of 5,000 screened compounds is approved as a new medicine. Success or failure in drug development often depends on selecting one or two molecules for development from many choices offered by the engines of high-throughput discovery. Drug development is a process that proceeds through several key go/no-go 'decision gates', from the identification of a potential therapeutic candidate through to marketing a drug product. Success rests not only in the intrinsic qualities of the molecule but also in how the drug's development is planned and executed, and in the effective management of key resources: effort, time and cost. Non-clinical studies form the basis for confidence in the safe and efficient progression of a new chemical entity into clinical testing. New in vitro methodologies that predict human response, coupled with time-tested protocols for drug testing in live animals and the emergence of sensitive analytical instrumentation and molecular genetics, play important roles in bringing safe and efficacious new drug candidates to market. This review discusses how to strategically identify which non-clinical studies should be performed to provide the required guidance and comfort to stakeholders involved in clinical drug testing. Drug development is a risky business. Success or failure often depends on selecting one or two molecules for development from many choices offered by the engines of high-throughput discovery. A lead candidate needs to possess adequate bioactivity, appropriate physical–chemical properties to enable formulation development, the ability to cross crucial membranes, reasonable metabolic stability and appropriate safety and efficacy in humans. Predicting how a drug will behave in humans before clinical testing requires a battery of sophisticated in vitro tests that complement traditional in vivo animal safety assessments. This review discusses how to strategically identify which non-clinical studies should be performed to provide the required guidance and comfort to stakeholders involved in clinical drug testing.