Control of Key Parameters in the Development of Mammalian Production Clones

The large scale production of recombinant proteins is mainly routed by the stability and production potential of the master cell bank. Biological safety of the product is accessed to the history of the cell line as well as to production conditions, down stream procedures and quality control. The quality of a recombinant cell line is assessed predominantly at the lab scale fermentation but at that time the physiologic and genomic status is already defined. For that reason it is inevitable to control parameters influencing the productivity and growth properties already during clone development. Clonal changes in transcriptional and translational behavior according to stress during selection and amplification have to be identified and comprised into the screening process. In different examples we have analyzed production titers and growth rates as well as genotypic variables concerning house keeping genes, selection markers and target genes providing information on the further development of recombinant clones.