ABSTRACT

At present animal-cell culture is used for the production of a large number of pharmaceutical proteins. With over 1200 proteins in clinical trials in 1998 this number is expected to increase in the coming years. As a consequence there will be an increasing demand for medium-and large-scale production facilities. For medium-(10 to 1000 litre)

and large-scale (>1000 litre) production, suspension cultures are being used mostly. The major concern in scale-up of suspension cultures is the supply of oxygen and removal of carbon dioxide. Gas transfer may be enhanced by the direct sparging of gas into the culture medium and by dispersing the gas bubbles using high agitation speeds. However, animal cells are relatively fragile compared to microbial cells due to their larger size and lack of a protective cell wall. As a consequence, the hydrodynamic forces generated during sparging and bubble dispersion cause damage to the cells.