Bioreactor and process design for large-scale mammalian cell culture manufacturing

Good Manufacturing Practice for pharmaceuticals requires that the manufacturing processes be controlled and reproducible. The biological nature of cell culture-based processes lends them an inherently higher variability than is generally found for processes involving production of defined chemical entities. As one regulatory body has pointed out, this places a greater emphasis on in-process controls and adherence to GMPs in the manufacture of cell culture products. Design of bioreactors and associated process control systems is a key element in the successful implementation of a commercial-scale cell culture manufacturing process capable of meeting such high standards. It should be noted that reactor and control system designs for animal cell culture are still very much in a state of evolution from the modified bacterial fermentation systems that currently predominate, and it is difficult to predict how design strategies may change in the coming years. Having said this, however, it should be clear from the information presented here that satisfactory processes can be devised today using proven equipment configurations such as the stirred-tank reactor.