Development of an impurity and hydrate form controlling continuous crystallization to telescope a two-step batch recrystallization in the GDC-4379 drug substance process

•A continuous process is developed to improve the rejection of a key regioisomer impurity during API crystallization.•The mechanism of regioisomer contamination in the crystallization product is experimentally determined.•Studies on the impurity contamination mechanism and kinetics drive the selection of an MSMPR crystallizer for the design.•97.9% of the regioisomer is rejected in the continuous crystallization compared to 32.4% in the equivalent batch process.•The capability to selectively crystallize the required hydrate form of the API in the continuous process is demonstrated.