May 6-11, 2018
Total sialic acid content (TSAC) is a critical product quality attribute (CQA) for a therapeutic protein. Previous studies and results have suggested lot-to-lot variability of raw material, media powder and feed, have potential effects on total sialyation acid content (TSAC) at cell culture fluid (CCF) and harvested cell culture fluid (HCCF). Through searching literature, we found that potential components in media powder and feed such trace metal and vitamins can greatly modulate the sialyation acid level in vivo or in vitro. For instance, the sialic acid content was simultaneously increased in glycopeptides as well as gangliosides under lithium treatment1. Moreover, supplementation of vitamin A, B, C and E were found significant correlation with sialic acid levels in variety of organisms2, 3, & 4. Therefore, an investigation was performed to further examine the relationship between TSAC level and suggested component Multivariate analysis was performed to identify metal and vitamin candidates that potentially have positive or negative effect on sialyation acid level. Top candidates will be selected and experiments will then be performed to carefully evaluate their impacts. We thereby aim to establish the efficient platform to screen for critical regulators of raw materials on TSAC level. This study will provide the insight of understanding better control of product quality and establishes a methodology for identifying the rooting causes in cell culture media contributing to the variability of cell performance.
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- Chitra et al. Indian Journal of Clinical Biochemistry 2008
- Qiao et al. J Nutr Vitaminol 2013.
- Tarthan et al. process Biochemistry, 2016
Wei-Chien Hung, Mei Shao, Bridget Leslie, John Mavrianos, Paul Loray, and Mei Shao, "Impact of raw materials on sialyation for a therapeutic protein" 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/149