Continuous viral inactivation: Understanding fundamental mass transfer enables simplified virus validation
October 6-10, 2019
As continuous bioprocessing rapidly approaches the opportunity to add to the global drug supply, establishing a robust continuous viral inactivation (CVI) step and associated validation testing is paramount. The use of a plug flow reactor possesses significant advantages over a multiple tank system in that the product spends less time low pH conditions; it provides the ability to sanitize between cycles; lacks air-liquid interfaces; and enables the 1-point standardization of the pH probe that provides the assurance of reaching the desired target pH. A critical parameter that poses a perceived new challenge is the definition of the exact incubation time of the product stream at production scale, as dispersion effects need to be accounted. Through extensive residence time distribution experimentation, the impact of viscosity, flow rate, and CVI reactor scaling parameters, flow characteristics were identified. This allowed the elucidation of the flow mechanics regarding the transition to weak turbulence inside the reactor due to Dean vortices. Leveraging the Dean vortices influence on dispersion, residence time for the product stream could be calculated allowing for the identification of worst case conditions (i.e. maximum and minimum residence time). The ultimate goal is to use the minimum residence time as the target inactivation time that will allow for a simplified batch based validation strategy in which the worst case conditions for a continuous viral inactivation step could be captured and quantified in a test tube, and be representative of the continuously operated system.
Matthew Brown, "Continuous viral inactivation: Understanding fundamental mass transfer enables simplified virus validation" in "Integrated Continuous Biomanufacturing IV", Veena Warikoo, Roche, USA Alois Jungbauer, BOKU, Austria Jon Coffman, Boehringer Ingelheim, USA Jason Walther, Sanofi, USA Eds, ECI Symposium Series, (2019). https://dc.engconfintl.org/biomanufact_iv/62