Chapter 4. Rapid Early Development of Potential Drug Candidates

Abstract

Process chemistry plays an extremely valuable role in the rapid development of potential small-molecule drug candidates from compound identification through to clinical proof-of-concept (POC). In all aspects of process chemistry enabling in this early development phase, the aim is not to develop the ultimate commercial route with in-depth process understanding and exquisite quality control. Rather it is to develop a fit-for-purpose process capable of supporting multikilogram synthesis with adequate control in a rapid timeframe to accelerate critical toxicology and clinical studies. A potential drug candidate can fail for many reasons during the early development phase, including safety, toleration and efficacy. Thus, a fit-for-purpose enabling paradigm is critical to drive speed and efficiency, providing a vibrant environment for the process chemistry community. This chapter outlines the key criteria and triggers for early process enabling in order to meet legislated safety, environmental, legal and control requirements, in addition to other key business efficiency requirements such as economic and throughput considerations. Through the use of effective criteria to trigger enabling activities, combined with rapid technologies to execute enabling packages, process chemists can play a critical role in delivering material rapidly to support toxicology and clinical studies. Once confidence in the drug candidate is achieved through a successful POC clinical study, the role of the process chemist then changes, as described in subsequent chapters.