Production of Recombinant Proteins and Monoclonal Antibodies in Hollow Fiber Bioreactors

The production of secreted products from mammalian cells such as recombinant proteins and monoclonal antibodies is generally performed in standard flask, roller or spinner culture. The typical cycle of seeding cells at a very low density in an excess of medium and then harvesting (often quite aggressively) just before the point of medium exhaustion, is itself a very unnatural system. It is only recently understood how dramatically culture conditions can affect protein quality. Popular culture systems take cells that originally grew attached to a porous matrix at high densities with little variability in per cell nutrient and oxygen supply and adapt them to low density styrene-bound or amorphous suspension culture. While well-understood, robust and convenient, classical batch-style 2-D culture on non-porous supports or 3-D suspension culture in other devices are really not very biologically relevant models. Cell culture conditions can affect the quality of the antibody or protein produced.