(191aj) Numerical Modelling Strategy for the Scale-up of Single-Use Bioreactors

Wave-mixed bioreactors have experienced increased importance in recent years in pharmaceutical processing. The low shear environment makes them particularly appealing for shear sensitive product. However, scale-up relationships between different sized mixing bags are not fully understood. It is advantageous to test the impact of the mixing process on high value product at a smaller scale before commencing production at large scale.

Numerical modelling, through the use of Computational Fluid Dynamics (CFD) was used to characterise the mixing times and hydrodynamic environment within a 500 mL and 50 L (production scale) mixing bag. The 50 L bag was characterised for a prescribed set of operating conditions (rocking speed and rocking angle of the wave bioreactor). Operating conditions for the small scale 500 mL mixing bag were identified that would generate the similar shear rates in both the 500 mL and 50 L mixing bag. Additionally, a scale-up relationship was developed. Validation experiments were then conducted at the 500 mL scale. This allows the high value product to be tested under the same shear environment at the 500 mL scale before processing at the 50 L scale.