Simulation of continuous low pH viral inactivation inside a coiled flow inverter

Abstract

Continuous production of monoclonal antibodies is gaining more and more importance. To ensure continuous flow through the entire process as well as viral safety, continuous viral clearance needs to be investigated as well. This study focuses on low pH viral inactivation inside a coiled flow inverter (CFI). Computational fluid dynamics (CFD) simulation is used to gain further insight into the inactivation process inside the apparatus. The influence of viruses in comparison to different tracer elements on the residence time distribution (RTD) behavior is investigated. Finally, the viral inactivation kinetics are implemented into the CFD simulation and real process conditions are simulated. These are compared to experimental results. To the authors' knowledge, this study represents the first successful simulation of continuous viral inactivation inside a CFI. It allows the detailed analysis of processes inside the apparatus and the prediction of experimental virus study results and will therefore contribute to the effective planning of future validation studies.

Continuous low pH viral inactivation: Operation and scaling strategy informs viral clearance study

“…In addition, affinity chromatography experiences self-sharpening peaks that can result in concentrated elution peaks. Like most companies that have defined an end-to-end continuous manufacturing process that incorporates a low pH CVI step (Coolbaugh et al, 2021;David et al, 2019David et al, , 2020, a mixing step occurs where a single ProA elution peak, which is shaped like an asymmetric Gaussian curve, is blended. This converts the feed material of the subsequent unit operations to be near homogeneous in composition and more reflective of a load material from a batch process with a pooling step.…”

Development of a transient inline spiking system for evaluating virus clearance in continuous bioprocessing—Proof of concept for virus filtration

“…Several researchers have begun to address the first challenge, for example, through the development of continuous flow reactors for virus inactivation or continuous chromatography systems for virus removal. For example, David, Maiser et al (2019) used a coiled flow inverter (CFI) with a narrow residence time distribution (RTD) for continuous inactivation of xenotropic murine leukemia virus (XMuLV), with the results in good agreement with model simulations developed using computational fluid dynamics (David et al, 2020). Similar results have been obtained with a packed bed continuous virus inactivation reactor using solvent/detergent mixtures for XMuLV and bovine viral diarrhea virus (Martins et al, 2019) and using low pH for XMuLV and pseudorabies virus (Martins et al, 2020).…”

“…Several researchers have begun to address the first challenge, for example, through the development of continuous flow reactors for virus inactivation or continuous chromatography systems for virus removal. For example, David, Maiser et al (2019) used a coiled flow inverter (CFI) with a narrow residence time distribution (RTD) for continuous inactivation of xenotropic murine leukemia virus (XMuLV), with the results in good agreement with model simulations developed using computational fluid dynamics (David et al, 2020).…”