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Impact of Dean Vortices on the Integrity Testing of a Continuous Viral Inactivation Reactor
Author(s) -
Amarikwa Linus,
Orozco Raquel,
Brown Matthew,
Coffman Jon
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.201700726
Subject(s) - tracer , materials science , chemistry , analytical chemistry (journal) , chromatography , physics , nuclear physics
We propose a standard protocol for integrity testing the residence‐time distribution (RTD) in a “Jig in a Box” design (JIB)—a previously described tortuous‐path, tubular, low‐pH, continuous viral inactivation reactor, ensuring that biopharmaceutical products will be incubated for the required minimum residence time, t min . t min is the time by which just 0.001% of the total product containing virus has exited the incubation chamber (i.e., t 0.00001 ). This t 0.00001 is selected to ensure a >4‐log reduction in viral load. As current tracers and in‐line analytical technologies may not be able to detect tracers at the 0.001% level, an alternative approach is required. The authors describe a method for deriving t min from t 0.005 (i.e., the time at which 0.5% of the product has emerged from the reactor outlet) and an experimentally confirmed offset value, t offset = t 0.005 − t 0.00001 . The authors also evaluate tracer candidates—including 100‐nm‐diameter gold nanoparticles, dextrose, monoclonal antibody, and riboflavin—for pre‐process acceptability and the effects of viscosity, molecular diffusion coefficient, and particle size. The authors show that a JIB will yield t min and RTDs that are nearly identical for multiple tracers due to Dean vortex induced mixing. Results indicate that almost any small‐molecule tracer that is generally recognized as safe can be used in pre‐use integrity testing of a continuous viral inactivation reactor under the Deans values (De) of 119–595.