Traditional process development and characterization typically involves risk-assessment (FMEA) followed by empirical techniques based on designed experiments to determine characterized ranges for unit operations in biopharmaceutical processes. While they are very effective these techniques still require considerable amount of resources and time. It is desirable to achieve first principles understanding of the process for improved robustness, predictability and optimization. We have been successfully advancing first principles modeling in the area of cation exchange (CEX) chromatography to mimic the results of wet experiments. The focus of this paper will be the review of our methodology of model development, studying of raw material variability, development of a filing strategy and an overview of feedback received from regulatory interactions. We will articulate how first principles modeling in bio/pharmaceutical process development could be implemented for reducing wet experiments, hence reducing development cycle time, improving process robustness and leverage advanced process understanding for process optimization and control opportunities using industrial case studies form CEX column.

First principles modeling towards accelerated process development: Experiences and prospects of computational model-based filing

251st National Meeting (2016)

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