(373b) Model-Aided Development for a Mixed Anhydride Formation in a Drug Substance Manufacturing Process

Mathematical models are valuable tools in process development to determine acceptable parameter ranges and control strategies for manufacturing. Some of the benefits of modeling in pharmaceutical development are its ability to reduce material costs and resource needs, while simultaneously increasing process understanding and quality control.

A case study is presented here that demonstrates the use of automated experimentation to gather high-value reaction data for kinetic parameter estimation of a six reaction step mechanism with nine components. The model was used to simulate kinetic and thermal profiles for varying addition strategies of a key reagent. The resulting model was used to define parameter targets and ensure process robustness in preparation for a successful registration stability campaign.