By taking advantage of their identical or similar post translational modifications to human, mammalian cells are considered as the main expression system for mAb production 2. Monoclonal antibodies (mAbs) have become the major biopharmaceutical products over the recent decade 1. Similar results were obtained during 250 L scale bioreactor culture, indicating the scalability of the approach.Ĭonclusion: The obtained results showed that pH fluctuations could be effectively controlled by optimizing CO 2 stripping. Accordingly, after increasing the agitation speed and headspace aeration, the culture pH was successfully maintained in the range of 6.95-7.1, resulting in 51% increase in final product titer. CO 2 accumulation was found to be affected by an interaction between agitation speed and overlay air flow rate. Results: The results indicated that the major factor affecting pH is non-efficient CO 2 removal. Subsequently, Central Composite Design (CCD) was employed to obtain a model for product titer prediction as a function of individual and interaction effects of significant variables. As culture pH directly influences process productivity, protein titer was measured as the response variable. Methods: Factors inducing partial pressure of CO 2 and lactate accumulation (as the main factors altering culture pH) were assessed by Plackett-Burman design to identify the significant ones.
IVCD CELL CULTURE SERIES
Accordingly, a series of experiments were conducted using an IgG1 producing Chinese Hamster Ovary (CHO-S) cell culture in 30 L bioreactor to assess the efficiency of an alternative strategy in controlling culture pH. Although CO 2 sparging and base addition are used as common approaches for pH control, these strategies are not necessarily successful in large scale bioreactors due to their effect on osmolality and cell viability. Biopharmaceutical Research Center, Aryogen Pharmed Inc., Alborz University of Medical Sciences, Karaj, Iranīiopharmaceutical Research Center, Aryogen Pharmed Inc., Alborz University of Medical Sciences, Karaj, Iran, Tel: +98 26 336106480 Drastic pH drop is a common consequence of scaling up a mammalian cell culture process, where it may affect the final performance of cell culture.
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