Understanding and improving cell culture processes through omi
May 6-11, 2018
Biologics remain the fastest growing class of pharmaceutics, with global market growth projected to exceed 400 billion dollars by 2025 . With this growth comes a need to manufacture diverse biological molecules to treat many serious diseases more cost effectively, and to deliver these medicines to the market quickly. Over the past 30 years, advances in life sciences and process engineering have directly contributed to advances in biologics manufacturing resulting in efficient processes with unprecedented protein titers. Nonetheless, common challenges still occur for many bioprocesses as they advance from early development through the process life cycle. This presentation discusses how omics technologies in conjunction with traditional monitoring techniques can be used to understand and improve cell culture processes . Here we present three case studies where Omics technologies were successfully applied to common bioprocessing challenges, including scale-up/down, product quality attribute control, and raw material variability. First, we discuss a legacy process which does not scale effectively between lab and manufacturing scales. In this case, metabolomics and proteomics approaches were used to identify a difference in oxidative stress levels at different scales, resulting in reduced viability, viable cell density and titer . This learning was then applied to the next generation process to successfully develop an optimized scale down model representative of manufacturing scale . Next, we show how Omics technologies can be used to increase both understanding and control of product quality attributes. We provide examples where metabolomics and transcriptomics were applied to improve cellular and process understanding around protein sialylation, a desirable glycosylation attribute , as well as α-Gal, an undesirable glycosylation attribute. In our third case study, we present a metabolomics approach to monitor raw material variability in a legacy process. Manufacturing lots for chemically defined and complex media components were analyzed using NMR and LC/MS, and age and storage related degradation metabolites were identified. The impact on process performance was confirmed through spiking studies. Finally, we propose strategies for incorporating Omics technologies into bioprocess development and manufacturing monitoring to enable long-term, sustainable improvements.
1. Biologics Market Size Worth $399.5 Billion By 2025 | Growth Rate: 3.9%: Grand View Research, Inc. TheStreet.
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4. Lewis, A.M., et al., Understanding and Controlling Sialylation in a CHO Fc-Fusion Process. PLOS ONE, 2016. 11(6): p. e0157111.
Amanda Lewis, "Understanding and improving cell culture processes through omi" in "Cell Culture Engineering XVI", A. Robinson, PhD, Tulane University R. Venkat, PhD, MedImmune E. Schaefer, ScD, J&J Janssen Eds, ECI Symposium Series, (2018). http://dc.engconfintl.org/ccexvi/218