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978-3-8439-4471-7, Reihe Technische Chemie
Viral clearance for continuous biopharmaceutical processes
265 Seiten, Dissertation Technische Universität Dortmund (2020), Softcover, A5
Continuous processing inside disposable equipment will be the future production method for monoclonal antibodies (mAb). Although most unit operations are already available in their continuous process mode, viral clearance is often neglected in the on-going discussion.
Two viral clearance steps are mandatory for mAb production processes, where low pH viral inactivation and viral filtration are the two standard steps.
The first step, low pH viral inactivation, is operated at pH levels < 4 for a certain inactivation duration. The coiled flow inverter (CFI) was used to provide this necessary inactivation duration in the continuous setup. A concept of a virus study for continuous low pH viral inactivation was developed and successfully tested. This study will be the basis for validation of this process step. Afterwards, computational fluid dynamics (CFD) simulation was utilized to gain deeper process understanding. New insights into the formation of Dean vortices were gained. Moreover, the continuous process conditions were further investigated by implementing the pH level distribution and viral inactivation process into the simulation. The results could be compared to the performed virus study. This method will decrease the experimental effort and more importantly enable the development of well understood, controllable and safe continuous viral clearance steps in the future. Finally, the helical flow inverter (HFI) was invented as a concept for a scale-up-ready device. With these results, low pH viral inactivation is now ready for implementation into continuous biopharmaceutical processes.
The second viral clearance step, viral filtration, was tested with phage studies, revealing the limitations of currently commercially available virus filters under these continuous conditions.
Finally, a side-by-side comparability study was performed, showing that batch and continuous processing lead to comparable product quality.