Effect of harvesting protocol on performance of a hollow fiber bioreactor

In this study, a bioreactor subject to Starling flow in closed shell batch harvest mode was compared to two forms of additional forced extracapillary (EC) space convection including EC circulation and EC cycling. Despite the presence of Starling flow as the dominant EC convection mechanism in the ba tch harvest system, the bioreactor start up was fairly good. However, the a ntibody productivity of the batch harvest system fell off rapidly after day 20 resulting in only 4.5 g of antibody produced. EC circulation with flow parallel to the fibers had a slightly better start up than the batch harves t. However, the antibody productivity also dropped after day 20 with EC cir culation, resulting in only 7.5 g of antibody produced. EC cycling with flo w both parallel and perpendicular to the fibers resulted in a start up simi lar to that of EC circulation. However, in contrast to the other two system s, antibody productivity in the EC cycling system was stable over the 60-da y experiment resulting in the production of 23 g of antibody. These results demonstrate the importance of inducing the proper flow distribution in the EC space to allow consistent and stable production in hollow fiber bioreac tors. (C) 1999 John Wiley & Sons, Inc.