(470d) Using Numerical Modelling (CFD) to Expedite Scale-up and Technology Transfer of Industrial Bioprocesses between Manufacturing Sites | AIChE

(470d) Using Numerical Modelling (CFD) to Expedite Scale-up and Technology Transfer of Industrial Bioprocesses between Manufacturing Sites

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Computational Fluid Dynamics (CFD) uses direct numerical simulations to solve problems involving fluid flows. APC has used CFD to facilitate rapid trouble shooting, scale up and technology transfer across a variety of equipment sets including mixing vessels, wave-bag reactors and TFF skids.

In this industrial application, three unit operations from a 300 L pilot plant process at a development site were transferred to a 1500 L process in a newly built manufacturing site. Significant differences in agitator geometries, liquid height aspect ratios and vessel design precluded the application of more traditional engineering correlations to ensure a successful transfer.

Numerical simulations of the sending site vessels at standard process conditions were completed, and a robust picture of the hydrodynamic environment in terms of shear and velocity profiles was generated. Due to the shear sensitive nature of the product in question, shear profiles during the corresponding unit operation from the sending site were used as a design constraint for the agitation strategy in the same unit operation at the receiving site. Agitation strategies were developed to achieve the required blend times without exceeding these shear constraints. An acceptable operating range was determined for each vessel and the impact of target agitation speeds on the process fluid at minimum and maximum fill levels was investigated.

Furthermore, a family approach was applied to vessels of similar aspect ratios and equivalent agitator design to identify potential agitation speeds for eight further vessels at the receiving facility, using traditional engineering correlations.

This approach allowed for robust agitation strategies to be developed without the need to conduct multiple at-scale mixing experiments. The results of the CFD simulations were validated using one confirmatory at-scale run and no further adjustments to the proposed agitation ranges were required.