Motivated by the need to reliably predict large-scale, cell culture performance for the production of recombinant proteins and monoclonal antibodies, we set out to refine our small-scale bioreactor model.  Our approach started by defining requirements for our model such as retaining product quality attributes across scales and matching trends in growth and productivity.  Next, we employed computational fluid dynamics (CFD) software in conjunction with a series of experiments to characterize each scale, focusing on: magnitude of shear forces, mixing time, bubble size distribution and liquid addition dispersion.  We explored the impact of modifying a host of operating conditions including: agitation rate, pH setpoint, dissolved oxygen setpoint, sparge rate, location of liquid additions (i.e. feed and alkaline solution) and timing of liquid additions.  Ultimately, we engineered our model to go from outperforming the large-scale by nearly 50% in terms of productivity to closely matching final titer while preserving product quality.

Iterating to a solution: Refinement of a small-scale bioreactor model

243rd National Meeting (2012)

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