Sunday, August 1, 2010
Pacific Concourse (Hyatt Regency San Francisco)
Shifting a mammalian cell culture process from hydrolysate-containing media to chemically-defined media has presented the challenge of defining cell sensitivity to certain hydrodynamic forces across multiple CHO cell lines. Previous scale-up experience using a hydrolysate process has shown one platform approach of aeration/agitation may be universally applied to multiple cell lines. The use of hydrolysate is known to provide a certain degree of protection against the shear induced forces that are present in stirred tank bioreactors. For chemically-defined processes, however, mass transfer aspects such as KLa, sparger design, sparge rate, gas entrance velocity, and carbon dioxide removal must be tailored to cope with a cell line’s proneness to shear damage. Case studies describing the scale-up of two different antibody producing CHO cell lines from bench-scale to pilot-scale were used to compare shear sensitivity between the two cell lines. A scale-down model to evaluate the cell line’s sensitivity to shear during early stages of development is established to assist in determining an appropriate scale-up strategy earlier and more efficiently. Once validated at the pilot scale, this strategy can be applied directly to the manufacturing scale.