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Continuous Solvent/Detergent Virus Inactivation Using a Packed‐Bed Reactor
Author(s) -
Martins Duarte L.,
Sencar Jure,
Hammerschmidt Nikolaus,
Tille Björn,
Kinderman Johanna,
Kreil Thomas R.,
Jungbauer Alois
Publication year - 2019
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.201800646
Subject(s) - residence time distribution , packed bed , static mixer , continuous stirred tank reactor , chromatography , trickle bed reactor , mixing (physics) , solvent , bioreactor , chemistry , residence time (fluid dynamics) , drop (telecommunication) , pressure drop , chemical engineering , materials science , process engineering , analytical chemistry (journal) , computer science , mechanics , physics , catalysis , biochemistry , engineering , telecommunications , inclusion (mineral) , mineralogy , geotechnical engineering , organic chemistry , quantum mechanics
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 scalability.