(406a) Rapid Process Development of a Pharmaceutical Intermediate for a Late-Stage Compound

During early stages in development, fit-for-purpose processes are often scaled up rapidly to meet aggressive timelines. While these processes exhibit robust performance in the laboratory, scale-up challenges may be encountered that require process modifications for subsequent campaigns. During the first pilot plant execution of a pharmaceutical intermediate process that consisted of 3-step telescope sequence, long cycle times were observed (~15 days per batch). Seventy percent of this cycle time was attributed to the final reaction step and crystallization / isolation. This talk will highlight how changes to the reaction chemistry allowed for a more streamlined work-up procedure and provided conditions that promoted crystal growth during the crystallization.  This talk will also show how DoE strategies and data visualization methods can be used to identify key factors affecting product quality, prove processing ranges, and identify optimal operating conditions. These methods afforded rapid process development on a short timeline that–when implemented at the pilot plant scale–resulted in cycle time reduction of 60-70% (~5 days per batch).