(283a) Leveraging First Principles to Advance Downstream Process Development and Understanding for Biologics

Improvements to how we execute a process development strategy can lead to reduced timelines as well as better process understanding, which helps to minimize manufacturing and patient risks. Aspiring to the best science at first filing, increased process knowledge has been gained through the implementation of high throughput techniques, process analytical technologies and modeling. Through the use of these workflows, the emphasis on chemical engineering fundamentals not only leads to the development of better processes but the development of better scientists and engineers. In Biologics development, a purification process platform is employed to enable speed to clinic and process efficiency, which can sometimes lead to an operational mindset. By grounding the work in first principles, we can encourage innovation and thoughtful development.

This talk will highlight ways that leveraging chemical engineering fundamentals can lead to more advanced process understanding and next generation development workflows. Specific examples include: i) predicting scale-up chromatography performance from miniature column data with the assistance of mechanistic models, ii) building a tangential flow filtration scale down mode using pressure drop as a scaling factor, iii) guiding the selection of harvest membranes or diafiltration buffer compositions, iv) understanding the impact of process variation on downstream unit operations and v) making informed choices for parameter classifications for process characterization. The insights gained in these case studies were the result of an intentional strategy to integrate first principles understanding with data-rich, high-throughput experimentation.