Computational fluid dynamics could enable effective and efficient scale up of gene therapy
Novel use of computational fluid dynamics to translate and scale-up bioreactor processes was found to be effective and comparable compared with small-scale manufacturing of gene therapy.
Computational fluid dynamics (CFD) has found a novel application in the scale up of advanced therapy production. Often applied to aerodynamics and weather simulation, CFD modelling has found to be effective in assessing 3D bioreactor hydrodynamics, enabling effective scale-up which could save time and money.
Ex vivo gene therapy requires cells containing the replacement or modifying genes to be expanded before administration to the patient. However, current methods of scale-up involve empirical, geometry‐dependent methods that may not accurately represent the hydrodynamics of 3D bioreactors, and may require multiple iterations of time-consuming and costly scale‐up studies.
In a study, CFD modelling was applied to the translation of induced pluripotent stem cells (iPSCs) from flask-scale to a bioreactor-scale, current good manufacturing practice (cGMP)-compliant process. CFD modelling was used to assess the hydrodynamics of the baseline 100ml spinner flask (Corning; NY, USA) and the 3L BioBLU 3c computer‐controlled bioreactor (Eppendorf; Hamburg, Germany).
The CFD analysis was found to accurately describe scale-up parameters, accounting for variables such as impeller type, addition of probes and volume, which geometric modelling is unable to do. Through implementation of the CFD-established parameters, human iPSCs were successful expanded, whilst maintaining their pluripotency, and further differentiated into cardiomyocytes.
“Although further optimization studies are required to exhibit the robustness of the scaled process”, the authors wrote, “we believe this proof‐of‐concept work is a major step forward in the development of affordable and commercial ready cell therapies derived from pluripotent stem cells.”