Scale-Up of Suspension and Anchorage-Dependent Animal Cells

In this chapter, scale-up is described in a laboratory context (10–20 L), but the principles and techniques employed have been successfully adapted so that cells are now grown industrially in unit volumes of up to 8000 L for vaccine, interferon, and monoclonal antibody production. The need to scale-up cell cultures has been expanded from the historical requirement for vaccine manufacture to include not only interferon and antibodies, but many important medical products such as tissue plasminogen activator and a range of hormones and blood factors. The low productivity of animal cells, resulting from their slow growth rate and low expression of product, plus the complexity of the growth conditions and media, led to attempts to use recombinant bacteria to express mammalian cell and virus proteins. However, this has proven unsuitable for many products, mainly because of incomplete expression and contamination with bacterial toxins, and more importance is now being put on expression of recombinant proteins from mammalian cells. This has allowed the use of faster growing and less fastidious cell lines, such as CHO, and amplification of product expression by multiple copies of the gene.