The pitched-blade system is traditionally the choice for stirred tank bioreactors in large-scale production of animal cells in suspension culture. The packed-bed basket technology developed by New Brunswick Scientific provides a shear-free environment for large-scale (up to 100 L) production of animal cells. At present, little information is available on the utility of this system for the production of secreted proteins, especially in perfusion mode of operation. The perfusion process provides a homeostatic environment for optimal cell growth similar to that experienced by cells in vivo. In contrast, the batch culture approach does not appropriately model this homeostatic environment due to the depletion of nutrients and accumulation of waste products in the culture system. Thus, the objective of this study was to compare the growth and productivity of alkaline phosphatase (ALKP)-secreting Chinese hamster ovary (CHO) cells cultured in these two bioreactor types: pitched-blade bioreactors operated in batch mode versus packed-bed bioreactors operated in perfusion mode. CHO cells cultured in the packed-bed bioreactor, operated in perfusion mode, produced greater amounts of ALKP compared to cells cultured in the pitched-blade system run in batch mode. These observations suggest that continuous exposure of cells to fresh culture media and the shear-free culture environment provided by the Fibra-Cel growth matrix disks offered more favorable growth conditions for CHO cells, allowing for either greater cell proliferation (higher density) or greater protein production on a per-cell basis. Overall, the results of this comparison study suggest that packed-bed bioreactors provide significant advantages for moderate-scale production of cells. The benefits of this bioreactor system may translate to large-scale cell culture for generating secreted protein products useful in medical applications…