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Heitmann, Martin

Marx, Nicolas

Nymand Nilsson, Claes

Rask Poulsen, Bjarne

English

Engineering Conferences International

Poster Number 241  DEVELOPMENT OF SCALE-DOWN SYSTEM FOR PERFUSION PROCESSES  Bjarne Rask Poulsen, Novo Nordisk A/S, Denmark bjrp@novonordisk.com Martin Heitmann, Sanofi-Aventis GmbH, Germany Nicolas Marx, University of Natural Resources and Life Sciences, Vienna, Austria Claes Nymand Nilsson, Novo Nordisk A/S, Denmark   Key Words: Perfusion, scale-down, chemostat, exponential increasing in-flow, discontinuous out-flow.  As a consequence of recent initiatives towards continuous bioprocessing, and since it often involves perfusion processes, there is an increasing need to scale these down and enable experiments with a decreased resource usage for each culture. In this poster, strategies are presented to enable screening of multiple process parameters, while focus is on simple, yet predictive, scale-down systems for perfusion processes. Due to the difficulty of implementing cell retention in small scale, it was decided to develop a chemostat scale-down system. The conception of a chemostat with exponential increasing in-flow and discontinuous out-flow (EIDO) yields a constant dilution rate (Figure 1). Its implementation in 10-15 mL scale ambrTM cultures is presented. The scale-down system is benchmarked towards bench top ATF perfusion cultures, illustrating the predictability of the scale-down system. The power of using chemostats to scale down perfusion is shown: the cells experience the same metabolite concentrations, and the same product concentration is observed, in the two systems, when the dilution rate in the chemostat is equal to the bleed rate in the perfusion. Therefore, this scale-down system can also predict product quality attributes.    Volume Dilution rate FlowFigure 1. Scaled-down chemostat culture with Exponential increasing In-flow and Discontinuous Out-flow (EIDO) 

Development of Scale-down system for perfusion precesses

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Development of Scale-down system for perfusion precesses

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Engineering Conferences International