INTERACTION OF CELL-CULTURE WITH DOWNSTREAM PURIFICATION - A CASE-STUDY

Separation of product from secreting mammalian cells in the culture br oth means the transition from product generation to product isolation. This interface within a biotech production process has to perform a p roper solid/liquid phase separation of the cell suspension to make the product containing fluid amenable for further purification. These sub sequent steps require fluid with low occurence of contaminants in orde r to function properly. The goal of this study was to evaluate some ec onomic and fast cell separation methods for the preparation of a produ ct fluid ready for use in further ultrafiltration and chromatographic processes. We have performed experiments to test the usefulness of dis c stack centrifuges and tangential flow microfiltration units at large scale. Both systems revealed outstanding prospects with regard to thr oughput and scale up properties. However, the centrificgation did not lead to a fluid sufficiently free of particles for direct ultrafiltrat ion or chromatography. Thus, an additional filtration step was necessa ry. On the other hand microfiltration led to an acceptable quality of process fluid directly. By optimisation of process parameters an effec tive, reproducible and robust cell separation can be obtained. However , our experience has been that such optimal conditions are somewhat sp ecific for a narrow range. Thus, even the equipment functioning well w ith one type of cell would possibly not perform as well with another c ell or even with the same cell under conditions slightly different to the usual situation.