Liaison(s): Semsi Ensari, Fikret Kulenovic
Centrifugation is a widespread and effective method for primary recovery in the production of biologic therapeutics. Prediction of industrial-scale centrifuge performance has been challenging as scale-up methods for centrifugation do not take into account the effect of shear on shear-sensitive mammalian cells. High levels of shear can cause rupturing of cells and the release of intracellular products that negatively impact the performance of following unit operation steps. In this project, computational fluid dynamics (CFD) is used to determine shear and its profile in an industrial-scale Alfa Laval Culturefuge 400. A scale-down shear device is developed to mimic the shear stresses generated in the centrifuge. The results obtained from the shear device are compared with those from the centrifuge under production conditions. The characterization of shear stresses through the use of CFD and the scale-down shear device provides a rational basis for evaluating the impact of shear on mammalian cells and can be used as a reliable predictor of scale-up primary recovery performance.