Part 3: Pilot and Manufacturing Scale Comparison of DynaDrive S.U.B. Capabilities

Introduction

Commercialisation of a drug is a monumental milestone that hinges on years of lifecycle management. As a product enters commercialisation, product sponsors are positioned to derive demand from a fluid market. Analysis of supply will inevitably question the cost of goods sold (COGS) and whether it is a process of scale-out or scale-up. In some cases, the decision must be made on how to scale up the process, which may require leaving the existing 2,000 L single-use bioreactor (S.U.B.) systems and moving the process into larger stainless steel vessels. Up until this point, there is a volumetric gap separating the single-use technology and stainless steel bioreactors. Existing 2,000 L S.U.B.s are supply chain limiting, while stainless steel systems can pose other challenges when demand remains fluid.

Modern process approaches have allowed increased product output, elevating titrespast 10 g/L in some cases. These output achievements require increased production efficiency and/or input, pushing many bioreactor systems outside of their operating capabilities. For example, as oxygen transfer rate (OTR) becomes a limiting factor, most traditional S.U.B.s rely primarily on increased sparging flow to increase oxygen mass transfer. Maintaining a dissolved oxygen (DO) target in high-demand cell culture can be difficult due to limitations in the amount of power that can be delivered through the existing drivetrain. Delivering the gas through a micro-sparger has become a strategy that is widely used to improve OTR in traditional S.U.B.s and typically requires a secondary sparger to facilitate the removal of dissolved CO₂ (measured as partial pressure of CO₂ or pCO₂). However, certain cell lines have been identified to be sensitive to the higher shear produced by micro-sparging, and thus, process scale-up should not depend on this method alone to ensure sufficient O₂ delivery or pCO₂ removal.