Continuous Culture with Macroporous Matrix, Fluidized Bed Systems
The development of the weighted, collagen microsphere, fluidized bed bioreactor system has produced an effective mammalian cell-culturing process. The cell-culturing technology utilizes continuous culture with immobilized cells inside a special matrix. The matrix is fluidized in a fluidized bed bioreactor. The fluidized bed bioreactor using the collagen microsphere matrix has been shown to be useful for many, if not all, cell types, both anchorage-dependent and suspension cell lines. The chapter provides the details of several production scale hardware configurations that use this technology. Several examples are presented showing data from runs using recombinant cells and hybridomas. These examples are given to illustrate scalability and productivity. Finally, an example is given to illustrate the production economics of this technology for an important pharmaceutical protein, tissue plasminogen activator (tPA). The fluidized bed bioreactor technology has been demonstrated at production scale by making tPA and monoclonal antibodies with excellent results as measured by daily output, product yield, product quality, and production cost.