A Systematic Approach to Enhancing Cell Culture Process Performance With a Productivity Exceeding 6.00 g/L/day of Therapeutic Antibodies

WuXi Biologics' Ultra-High Productivity Platform (WuXiUP) is an innovative and integrated continuous biomanufacturing platform. It encompasses a comprehensive suite of strategies to enhance the upstream and downstream development of a variety of biologics with remarkably improved productivity and product quality. In this study, a methodology was proposed in order to create a general roadmap for high-productivity process development applying this systematic approach, and explore the potential of this platform in achieving higher productivity. The optimized process was successfully demonstrated at 50 L scale. The approach is to categorize all potential key parameters into perfusion-related and non-perfusion-related groups, and apply modularized optimization to facilitate and simplify the development progress. In the proof-of-concept experiment, a significant increase in cell culture productivity was achieved for a mAb molecule at the lab scale. The process was then successfully scaled up at the pilot scale (50 L), ultimately achieving a productivity exceeding 110.00 g/L over an 18-day production phase, with an average daily productivity surpassing 6.00 g/L/day. This successful application demonstrates the industrial applicability of the WuXiUP process optimization methodology, confirming its effectiveness in accelerating WuXiUP process development and further boosting productivity.