(649a) Kinetic Model Driven Optimization and Control of a Hydrogenation Reaction System

Chemical reactions exist at the heart of every API manufacturing process. However, significant hurdles may exist for the development and optimization of reliable reactions, including highly complex reactions sensitive to a high number of variable factors and limitations on resources in terms of time and cost. The system described in this work involves a catalytic hydrogenation reaction in which an impurity is generated over the course of the reaction. Because of limited purge for that impurity, reaction level control and minimization of the generation is necessary. Balancing minimization of the impurity generation with production of the desired API is critical in the optimization of this reaction. Here, we describe our efforts to overcome these challenges by developing a robust kinetic model to represent the reaction system. The model is used in the formulation of an optimization problem to control the reaction profile over time by fitting an idealized dynamic temperature profile. Using the optimized temperature profile, the hydrogenation reaction consistently produced the desired product within required purity ranges, while production of impurities and intermediates remained controlled. Results presented include a description of the development and performance of the hydrogenation kinetic model, in addition to a comparison of the model predicted performance of the optimized temperature profile to experimental results. This work demonstrates the tremendous potential for reaction level model-based control in pharmaceutical manufacturing.