Hydrodynamic design space for process transfer across different bioreactor platforms

The increasing diversification of bioreactor platforms in biopharmaceutical manufacturing, including stirred-tank, 1-D rocking, and orbital-rocking systems, has created challenges for transferring processes across systems with fundamentally different mixing mechanisms. Conventional scale-up parameters, such as power input per unit volume (P/V), are well established for stirred-tank reactors (STRs), but impeller-based methods for estimating P/V are not directly applicable to impeller-free systems. In this study, a computational fluid dynamics (CFD)-based framework was developed to define a hydrodynamic design space for process transfer across stirred-tank (STR), 1-D rocking (RM20), and orbital-rocking (CELBIC50) bioreactor systems. Power dissipation per unit volume (Pd/V) was proposed as a platform-independent energy dissipation parameter and combined with shear stress and mixing time to define feasible operating regions. Using this framework, operating conditions could be identified across different bioreactor types using a multi-constraint hydrodynamic design space. Hydrodynamic analysis revealed distinct flow characteristics among the bioreactors, with CELBIC50 exhibiting lower mean shear stress (0.012 vs. 0.019 Pa) and a shorter mixing time (80.9 vs. 146.6 s) than RM20 under the selected operating conditions. Despite these differences, fed-batch CHO cell cultures under the selected conditions showed comparable cell growth, productivity, metabolite profiles, and product quality across STR 2 L, RM20, and CELBIC50, with most performance variables remaining within the common ± 2 σ range. These results demonstrate that a multi-constraint hydrodynamic design space integrating Pd/V, shear stress, and mixing time provides a quantitative framework for identifying transferable operating conditions across different bioreactor systems and supports model-informed process development. Key points • Hydrodynamic characteristics were systematically compared across stirred-tank, 1-D rocking-motion, and orbital-rocking bioreactors under diverse operating conditions. • Pd/V was proposed as a platform-independent energy dissipation parameter across different bioreactor systems. • A constraint-based hydrodynamic design space integrating Pd/V, shear stress, and mixing time was developed for systematic bioprocess transfer.