(446d) Development of a Kinetic Model-Based Tool for Enhanced Process Understanding and Justification

In drug substance process development, establishing a robust control strategy is of utmost importance. While the program advances through the stages of development, important process parameters are identified and justified by means of thorough experimentation. To drive towards greater understanding of the process in an efficient manner, the ability to design and conduct data-rich experiments has become and essential target for project teams. A practical means to reach this target is the development of kinetic models, which simultaneously incorporate physical and chemical phenomena of relevant reactions. Using a kinetic model, it is possible to predict the impact of changes in process parameters on the process outputs and identify the sets of conditions that would strain a process to its limits. Consequently, when combined with existing process understanding, kinetic models can be employed in justifying parameter ranges for processes.

In this presentation, we illustrate the development of a kinetic model-based tool that is utilized to obtain enhanced process understanding and to support the control strategy. Combination of a kinetic model with a spreadsheet-based, user-friendly template provided the ability to predict the impact of parameters on the process outputs in cases when one or more parameters are simultaneously changed from their nominal values. The tool was also utilized to identify potential failure points. Enhanced process understanding generated by utilizing this tool was implemented in the process control strategy to improve process robustness at the commercial manufacturing scale.