(234g) Looking inside and out: Addressing Bioprocessing Challenges in the Biopharma Industry

With the expanding use of mammalian and other eukaryotic cells for biologics production in intensive processes, it is important to understand both the intracellular and extracellular environment to enhance overall process performance. This can be achieved through a combination of methodologies to characterize the process parameters, including media conditions and the CHO cells used along with genetic interventions where appropriate. Process intensification increases the demand for media with highly concentrated levels of nutrients necessary to optimize cell growth and antibody production. However, the use of high concentrations of particular nutrients may present unique challenges both in terms of nutrient solubility as well as chemical interactions within the media environment. Understanding the conditions for media solubility can be useful in designing an optimized media formulation, and characterizing the chemical nature of this media will allow us to determine how the media components affect cell growth and productivity. Additionally, understanding how the cells utilize these components will allow the users to reliably estimate how much of each of the nutrients is needed for batch, fed-batch or perfusion operations. Our goal is to apply systems level models to assist bioprocessing experts in negotiating the landscape of cells and their media as part of increased process intensification. We are also evaluating the use of analytical methods for validating these predictions in order to have a better understanding of the forms of chemical complexes in the media. In addition, we are evaluating how CHO cells utilize these nutrients as inputs into cell growth and production. Through genome scale models, we are mapping CHO metabolic pathways and implementing these models to investigate how nutrients are being used in culture. Finally we are applying genetic engineering strategies to improve the performance of different cell types. Many of these projects are underway as part of AMBIC (AMBIC.org) and IBiONe initiatives, an academic-government-industrial consortium and international network, respectively, dedicated to addressing early stage research in upstream biomanufacturing. Focal areas include: 1) understanding industrially-relevant biology, 2) process monitoring and control, and 3) consensus and standardization for advancing upstream biomanufacturing. This presentation will discuss the activities within AMBIC and beyond as we take an introspective and extrospective look at improving performance in cell culture systems now and going forward.