Scale Related Variables and Their Potential Impact on Process and Product Quality in the Production of Biologics

Cell culture technologies for the production of recombinant protein therapeutics have evolved over the years and span from batch to fed batch, perfusion and other production methods. Process intensification has resulted in new challenges during process scale-up. We assessed dissolved oxygen and pH control strategies at 2-L, 100-L and 2000-L scale to evaluate process and product consistency across the three scales. Differences in mass transfer characteristics and offline sample handling across the scales caused up to 20% differences in integral viable cell density. The changes in the cell growth profiles resulted in shifts in product glycan profiles and associated effector function attributes. Understanding the cell culture operating space based on the selected production method and associated control variables is key to successful process scale-up.