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\begin{document}

\title{Residence time distribution in continuous virus filtration}



\author[1]{Alois Jungbauer}%
\author[1]{Yu-Cheng Chen}%
\author[1]{Gabriele Recanati}%
\author[1]{Fernando De Mathia}%
\author[2]{Dong-Qiang Lin}%
\affil[1]{Universitat fur Bodenkultur Department fur Biotechnologie}%
\affil[2]{Zhejiang University College of Chemical and Biological Engineering}%


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  \date{June 13, 2024}


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\begin{abstract}
Regulatory authorities recommend using residence time distribution (RTD)
to address material traceability in continuous manufacturing. Continuous
virus filtration is an essential but poorly understood step in biologics
manufacturing. Here we describe a model that considers non-ideal mixing
and film resistance for RTD prediction in continuous virus filtration,
and its experimental validation using the inert tracer NaNO
\textsubscript{3}. The model was successfully calibrated through pulse
injection experiments, yielding good agreement between model prediction
and experiment ( R 2 \textgreater{} ~ 0.90). The model enables
prediction of RTD with variations---e.g., in injection volumes, flow
rates, tracer concentrations, and filter surface areas---and was
validated using stepwise experiments, and combined stepwise and pulse
injection experiments. All validation experiments achieved R 2
\textgreater{} ~ 0.97, except when valves were switched at a high flow
rate. Notably, if the process includes a porous material---such as a
porous chromatography material, ultrafilter, or virus filter---it must
be considered whether the molecule size affects the RTD, as tracers with
different sizes may penetrate the pore space differently. Calibration of
the model with NaNO \textsubscript{3} enabled extrapolation to RTD of
recombinant antibodies, which will promote significant savings in
antibody consumption. This RTD model is ready for further application in
end-to-end integrated continuous downstream processes, such as
addressing material traceability during continuous virus filtration
processes.%
\end{abstract}%



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\textbf{Hosted file}

\verb`Modeling of VF-RTD_06.docx`  available at \url{https://authorea.com/users/596738/articles/723244-residence-time-distribution-in-continuous-virus-filtration}

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