(299a) Intensification of a Continuous Process Guided By Mechanistic Modeling

Manufacturing of Active Pharmaceutical Ingredients (API’s) is commonly performed in batch mode, a reality that limits the application of some chemistries or the efficiency of processes that rely on fine control of parameters, for example, to avoid formation of impurities. Flow chemistry and continuous manufacturing represent a viable alternative to overcome these limitations. Here, mass and heat transfer are much improved over batch, allowing process intensification of small volumes of mixture over time in a safer and efficient manner.

To gain knowledge in the field of flow chemistry, Hovione started by translating key processes developed in-house to continuous. This work presents a case study embedded in our Quality-by-Design (QbD) approach, where process intensification was applied to convert a batch reaction to continuous. This project was selected due to a high exotherm that raised safety concerns when planning scale-up. The data available from the batch process was utilized to build the kinetic model of the reaction and guide the first stages of development in flow. This allowed us to achieve a process with similar efficiency to the original batch process without much experimentation. Opting for a development approach based on mechanistic modeling, we were able to highlight a change on the reactivity profile of this process as a consequence of working in a different experimental space.