As discussed in Chapter 2, specific protein production (pg/cell/hour) can be dramatically increased by the creation of more efficient producer cells which are capable of high-level transcription coupled with fast and accurate processing and a secretory capacity of matching performance.

However, producing commercial quantities of recombinant protein even by the most productive cells still requires large-scale cell cultures. This need has led to the rapid and continuing development of new approaches to mass cell culture and has been instrumental in dispelling certain dogmas concerning the impracticality of commercial production from animal cells. It has also led to an ongoing re-evaluation of product generation from animal cells according to more sound bio-engineering principles.

Small-scale, low-density animal cell cultures in classical serum-containing medium are relatively simple systems to operate. Since the metabolism of the cells is slow, oxygen demand can be satisfied by simple diffusion or slow stirring, pH changes are slow and easily controlled by buffering and the effect of the production of toxic substances and of proteases are largely abrogated by the absorption and inhibitory capacities of serum.

This situation changes dramatically when large quantities of cells are cultured intensively for the industrial production of kilogram quantities of recombinant proteins and all of these parameters are pushed to new limits. This chapter considers the progress that has been achieved in the key areas to satisfy these demands and discusses the problems that remain and some possible solutions.