Continuous Solvent/Detergent Virus Inactivation Using a Packed-Bed Reactor

Biotechnology Journal
Duarte L MartinsAlois Jungbauer

Abstract

Continuous virus inactivation (VI) remains one of the missing pieces while the biopharma industry moves toward continuous manufacturing. The challenges of adapting VI to the continuous operation are two-fold: 1) achieving fluid homogeneity and 2) a narrow residence time distribution (RTD) for fluid incubation. To address these challenges, a dynamic active in-line mixer and a packed-bed continuous virus inactivation reactor (CVIR) are implemented, which act as a narrow RTD incubation chamber. The developed concept is applied using solvent/detergent (S/D) treatment for inactivation of two commonly used model viruses. The in-line mixer is characterized and enables mixing of the viscous S/D chemicals to ±1.0% of the target concentration in a small dead volume. The reactor's RTD is characterized and additional control experiments confirm that the VI is due to the S/D action and not induced by system components. The CVIR setup achieves steady state rapidly before two reactor volumes and the logarithmic reduction values of the continuous inactivation process are identical to those obtained by the traditional batch operation. The packed-bed reactor for continuous VI unites fully continuous processing with very low-pressure drop and sca...Continue Reading

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Citations

Dec 24, 2019·Biotechnology and Bioengineering·Laura DavidGerhard Schembecker
Feb 6, 2020·Biotechnology and Bioengineering·Duarte L MartinsAlois Jungbauer
Apr 18, 2020·Biotechnology Journal·Jure SencarAlois Jungbauer
Jan 11, 2020·Frontiers in Bioengineering and Biotechnology·Nagesh K Tripathi, Ambuj Shrivastava
Jan 8, 2021·Journal of Chromatography. a·Julia Scheffel, Sophia Hober
Mar 23, 2021·Biotechnology and Bioengineering·Mariana N São PedroMarcel Ottens
Jun 9, 2021·Biotechnology and Bioengineering·Moo Sun HongRichard D Braatz

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