(69g) Optimizing Biologics Production and Quality: Investigating the Role of Trace Elements in Mammalian Cell Expression Systems

Mammalian cells, particularly Chinese Hamster Ovary (CHO) cells, are widely used for the biologics production. To optimize the productivity and quality of these biologics, it is crucial to have an optimized cell culture media that supports both cell growth and high expression of biologics. This study aimed to investigate the effect of trace elements (iron, zinc, copper, selenium, and manganese) in the cell culture media. A fed-batch process with CHO cells was used as the process model, and a definitive screening design was employed to explore the impact of different trace elements independently. Additionally, the custom media powder sourced from two different vendors was also evaluated.

The findings of this study revealed that iron (Fe) significantly promoted cell growth and enhanced productivity. However, it was also observed that Fe had significant impact on the product quality, specifically affecting the percentage of acidic charge variants of the product. Zinc was found to promote cell growth but did not result in increased titer. On the other hand, copper (Cu) significantly improved the titer by enhancing the TCA cycle activity and suppressing lactate secretion. Manganese affected N-glycan galactosylation, while selenium showed no significant effect within the tested range. Some of these effects were also observed in a cell line derived from different CHO host, indicating the universal impact of the findings. Furthermore, the study demonstrated that the choice of feed vendor had a significant impact on both culture performance and product quality. Residual trace element analysis using ICP-MS highlighted the importance of controlling the variability of raw materials.

In summary, this study demonstrates the systematic investigation of the impact of trace elements in cell culture media on CHO cell growth, productivity, and product quality using DOE approach. The findings highlight the importance of optimizing trace element concentration and controlling raw material variability for maximizing biologics production in mammalian cell expression systems.