Mammalian Cell Cultivation

Bioreactors developed for mammalian cell culture use a smooth surfaced ceramic for the growth of adherent cells or a porous ceramic for the immobilization of suspension cells. Mammalian cell culture technology has been used for the production of viral vaccines, monoclonal antibodies for diagnostic and therapeutic use, interferons, interleukins, growth factors, and blood regulation proteins. The design of novel bioreactors for mammalian cell culture must take into consideration process constraints such as cell line distribution, product formation, oxygen transfer, nutrient supply, and shear. A viable alternative to scalable mass cell culture is the use of bioreactors with ceramic matrices. Immobilization of adherent and suspension cells on these surfaces has resulted in the favorable production of both cells and cell derived proteins. Cell culture densities ranging from 2 X 106 cells per mL (spinner flask culture) to 1 X 108 cells per mL (high density perfusion reactors) have been obtained (155).

For the cultivation of anchorage dependent animal cells, packed bed bioreactors have been used. Such reactors up to 100 L in size have been successfully operated with BHK 21 C13 monolayer cells for the production of foot-and-mouth disease virus vaccine antigen (156). In a commonly used packed bed bioreactor, glass beads ensure adherence and subsequent colonization in situ (157). The use of polyester or polyurethane foam matrices (158) for the culture of hybridomas ensures passive entrapment of the cells in the inert matrix with the added advantages of perfusion of cells with fresh medium, increased process intensity, and improved downstream processing. The first airlift fermentor (1000 L scale) to produce monoclonal antibodies from hybridoma cells in suspension was developed by Celltech (159).

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