First-Generation Process Development of Napabucasin and Impurity Control Strategy

The manufacturing process for napabucasin described herein produced drug substance reliably on a scale up to 100 kg. The purification strategy employed was effective at removing process-related impurities and consistently afforded drug substance that met specifications. Below, we present an overview of the process development history and the impurity control strategy that was implemented to achieve robust manufacturing performance. Critical process parameters were identified, and process-related impurities and their proposed mechanisms of formation are presented.