Current Considerations and Future Advances in Chemically Defined Medium Development for the Production of Protein Therapeutics in CHO Cells

Cell culture media support propagation or scale‐up of CHO cell inoculum and production of biotherapeutic molecules. Formulations and compositions of culture media vary from complex undefined (i.e. media containing serum and animal‐ or plant‐derived hydrolysates) to defined (i.e. distinct chemicals) in nature. Many biopharmaceutical manufacturers have moved away from media that contain animal‐derived components to mitigate introducing adventitious agents into the final products and media containing plant‐based hydrolysates to reduce lot‐to‐lot variability of raw material, which may impact final productivity and product quality. Chemically defined (CD) media have become the preferred choice for biologics manufacturing. However, development of CD media is not devoid of challenges. CD media can be sensitive to changes in raw material sources, medium mixing and blending processes, and storage conditions (duration, temperature, oxygen, and light exposure). Therefore, precautionary controls should be included as part of medium development operations to ensure handling consistency. In addition, long‐term media storage and stability are critical factors in CD medium formulation development. During development, bench‐scale evaluation is typically conducted. However, consistent performance must be established for large‐scale use. Long‐term storage, storage containers, and powder media hydration protocols should be considered. Raw material batch‐to‐batch consistency in both supplier sourcing and impurity contaminant control is a focus of CD medium development to ensure consistent final product quality. This chapter will discuss practical aspects for developing chemically defined media for CHO cells as well as provide an outlook on the role of systems biology in developing the next generation of media and production processes.