September 17-21, 2017
Perfusion medium development is complex and time-consuming. Thus, a methodology for efficient and cost effective development leading to a significant reduction of time to market is key in today's competitive market. Success in perfusion medium development depends strongly on the choice of optimization tools. Here a streamlined strategic approach to accentuate perfusion media development is presented by means of predictive scale down models and the application of Design of Experiments (DOE). The purpose of the study was to investigate the impact of 19 amino acids on productivity and growth of a CHO-K1 cell line in perfusion cell culture. A stepwise approach for screening, optimization and robustness testing of optimal media conditions was used for systematic planning, execution and statistical evaluation of experiments. We developed a high throughput semi-continuous scale-down model (SDM) predictive of perfusion bioreactor operation. This predictive tool allows to minimize the risk that findings in screening and medium development do not translate into bioreactor processes. Optimal perfusion media conditions were identified for cell growth and productivity based on a definitive screening design with three concentration levels (Jones & Nachtsheim, 2011) followed by a classical central composite design (Box-Wilson, 1951) for fine tuning the optimization exercise. This approach provided an efficient way of screening a large number of medium supplements while significantly reducing the number of experiments required, thus accelerating time to market and reducing costs. These optimum conditions lead to significant improvements in productivity and cell growth at different scales.
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Jochen Sieck, Christian Schultheiss, and Pedro Felizardo, "Optimizing media for perfusion combining predictive scale-down models and multivariate approaches" in "Integrated Continuous Biomanufacturing III", Suzanne Farid, University College London, United Kingdom Chetan Goudar, Amgen, USA Paula Alves, IBET, Portugal Veena Warikoo, Axcella Health, Inc., USA Eds, ECI Symposium Series, (2017). https://dc.engconfintl.org/biomanufact_iii/54