Principal Research Scientist AbbVie North Chicago, Illinois
This presentation highlights unique features and key challenges encountered during the development of upadacitinib to bring this molecule into the clinic. Upadacitinib is a small molecule with the classic rule of five properties, but it embodies key challenges at the frontier of organic solid-state chemistry, including the difficulty of crystallization and the formation of multicomponent crystal forms (i.e., solvates/hydrates). Fit-for-purpose crystal form and formulation were initially used to enable clinical studies. The course of action taken throughout development to meet project deliverables is described. Herculean efforts and tailored designed experiments were conducted leading to a late discovery of a stable crystalline hydrate. Enhanced molecular level elucidation of the thermodynamics of solid form underpinned a robust drug substance manufacturing process. The scientific journey of upadacitinib unfolded into the development of a sound derisking strategy to manage drug substance and drug product processing requirements.
Learning Objectives:
Learn challenges and key takeaways that can inform drug development from preclinical to market application
Learn how to overcome hurdles in finding a viable crystalline solid form and manage the robustness of a solid form during development
Learn how to efficiently choose after a drug candidate selection a manufacturing process that provides the balance between drug substance process and formulation manufacturability requirements to enable clinical studies
