In this project we will use new Industry 4.0 capabilities to drive more rapid
discovery and optimisation of chemical processes to facilitate the move toward a carbon negative vision by utilising microvolume pulses in flow reactors for automated chemical development.
This project aims to deliver microscale automation for the next generation of medicine development by developing Industry 4.0 platforms capable of optimising multi-operation sequences (unlocking purification and complex chemistry) throughout drug development pipelines. The challenge of improving chemistry productivity in both discovery and development is heightened by the increasing complexity of small-molecule drugs. Testing key hypotheses in drug development programmes requires efficient access to specific, carefully-designed routes that require multiple cycles of synthesis optimisation. The vast majority of such routes currently need to be evaluated manually, often via lengthy time-consuming experimentation, because current automated chemistry capabilities are restricted to single-step syntheses involving homogenous reactions. As a consequence, current practices induce medicinal chemists to harness a narrow toolkit of reliable chemistry which limits the diversity of molecules that may be explored. This greater molecular
complexity has also driven an increase in the length of manufacturing routes (from 8 to 16 steps on average in the last decade). The rapid identification of a manufacturing route, and its regulatory approval, is critical, and accelerated clinical trials can force adoption of sub-optimal routes. Removal of a single manufacturing step (typical yield: 90%) would reduce costs and waste by ~10%, a benefit that is compounded for every step removed.
The ability to move rapidly from drug discovery through to commercially-viable manufacturing is vital in delivering new drugs to patients. Yet, many decisions made during discovery have unforeseen consequences on manufacturing: frequently, synthetic routes have to be re-designed, which can lead to inefficient processes (time, cost, environmental burden). Our accelerated approach will retain the essential goal of each stage within the development pipeline, but address the difficult transition from large numbers of compounds to a single clinical candidate.
This project is part of an initiative at the University of Leeds with AstraZeneca and UCB Pharma supporting 4 PhD positions and a PDRA starting in 2021.