November 1-5, 2015
Reaching cell densities higher than 80 million with the minimum possible perfusion rates is a goal for an increasing proportion of processes developed by biopharmaceutical companies. With the goal of fulfilling the industry needs for better commercial and customized perfusion media, SAFC evaluated different small-scale perfusion models to achieve an efficient work flow that can accommodate perfusion systems. SAFC successfully uses an optimized work flow for the development of media and feeds for fed-batch cell culture that integrates high-throughput screening, statistical tools and bench-top bioreactor scale studies. In this model, 96-deep well plates are used for the initial high throughput screening, followed by further development in spin tubes or shake flasks. At this time, there is no commercially available cell separation device that can be used for scales of 30mL or lower. The application of the 96-deep well plate or spin tubes model for perfusion showed to have severe limitations, specifically when trying to optimize processes to extremely low cell specific perfusion rates (CSPR). In order to develop media that can sustain the desired high densities and productivity at the desired low CSPRs, we needed a representative model that provided enough throughput to apply our statistical analysis. With this goal, we evaluated an alternative small scale model using the automation and process control offered by the ambr15TM. In this work, we show how ambr15TM fits in the work flow for perfusion media development and its comparability to bioreactor perfusion at high cell densities using ATF.
Dustin Davis, Delia Lyons, and Scott Ross, "Modeling perfusion at small scale using ambr15TM" in "Integrated Continuous Biomanufacturing II", Chetan Goudar, Amgen Inc. Suzanne Farid, University College London Christopher Hwang, Genzyme-Sanofi Karol Lacki, Novo Nordisk Eds, ECI Symposium Series, (2015). http://dc.engconfintl.org/biomanufact_ii/128