(138b) Development and Control of a Late-Stage API Crystallization Via Kinetics Modeling and Controlled Crystallization

To supply the early developmental batches for clinical trials, a fit-for-purpose API process step included an ammonolysis reaction followed by uncontrolled crystallization – involving crash-out of the API due to its poor solubility in the system. This crude crystallization was followed up by a recrystallization step in a different solvent matrix – allowing for polish filtration and reprocessing options. The impurity purging with either the crude or the recrystallization steps were not great. As the program advanced, an alternate process was developed with an aim to streamline, robustly scale-up, and help establish impurity control. The new process utilized a kinetics model to enrich the reaction understanding and ensured that a controlled crystallization was possible post reaction that allowed for a better impurity purging. This talk aims to focus on the developmental aspects of this journey, highlighting the motivation, challenges, and process improvements for the same.