(240f) Application of CFD Modeling for the Development and Transfer of Mixing and Compounding Processes with Single Use Equipment

Pharmaceutical Discovery, Development and Manufacturing Forum

26006 Advances in Large Molecule Processes - Oral Session –

Application of CFD Modeling for the development and transfer of mixing and compounding processes with single use equipment

Mario Hirth^1*, Kushal Sinha², Nandkishor Nere², Martin Bultmann¹

*presenter: Mario.hirth@abbvie.com

¹AbbVie Deutschland GmbH&Co KG, Knollstraße 50, 67061 Ludwigshafen

²AbbVie, 1401 Sheridan Road, North Chicago, Il 60064

Mixing is one of the most important unit operations in drug-product processes for large biological molecules as it assurers homogeneity of parenteral drug products in pooling and for additional compounding steps. In order to achieve successful scale-up and technology transfer from development to commercial scale of mixing process, it is crucial to understand the hydrodynamics as a function of equipment and drug substance. Single-use mixing systems are becoming an important option in manufacturing of large molecules for conventional mixing vessels due to the many advantages that come with disposable systems like reduced cross-contamination risk and shorter batch changeover times. The main challenge when transferring large molecule processes from stainless-steel to single-use vessels is insufficient knowledge of the equipment related performance. Computational Fluid Dynamics (CFD) is a well-established and powerful tool to characterize the mixing performance in single-use systems.

In this study, CFD-modeling was applied to study and predict the hydrodynamics of different types and sizes for single-use mixing system applicable from development to manufacturing scale. Understanding the fluid dynamics by CFD in those tanks is a crucial factor to understand the blending, intensity and duration of shear exposure. We present here the results from 5 different single-use mixing systems with a working volume of 50 L, 100 L and 200 L. Flow pattern and mixing performance were predicted as a function of viscosity, fill volume and agitation speed. Tracer simulation was applied to indicate how process parameters affect the mixing duration in the tank. A bolus tracer was injected and the distribution was monitored at several locations to calculate blend time and to identify poor mixing zones for each single-use system. The results can be used to recommend ideal mixing conditions up to batch sizes from 6 L to 200 L. In addition, lab trials were conducted to verify the CFD model. Results show that the CFD approach generates a profound understanding what happens inside the different reactor scales. As a result scale up and tech transfer of mixing and compounding processes get more robust and offer the possibility to decrease the amount of effort and API for mixing validation.

All authors are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.