Effects of perfusion processes under limiting conditions on different Chinese Hamster Ovary cells

Background The use of perfusion culture to generate biopharmaceuticals is an attractive alternative to fed-batch bioreactor operation. The process allows for generation of high cell densities, stable culture conditions and a short residence time of active ingredients to facilitate the production of sensitive therapeutic proteins. However, challenges remain for efficient perfusion based production at industrial scale, primarily complexity of required equipment and strategies adopted for downstream processing. For perfusion systems to be industrially viable there is a need to increase product yields from a perfusion-based platform. We have shown previously that one effective way to enhance the cell specific productivity is via glucose limitation [1,2]. The mechanisms leading to an increased productivity under these glucose limiting conditions are still under investigation. Preliminary studies using proteomic analysis have indicated changes in histone acetylation [2]. In this work, we investigated the influence of glucose limited conditions on the production of two different recombinant proteins in perfusion processes.