Residence time distribution in continuous virus filtration

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 in respect to fluid dynamics and scale‐up. Here we describe a model that considers nonideal mixing and film resistance for RTD prediction in continuous virus filtration, and its experimental validation using the inert tracer NaNO3. The model was successfully calibrated through pulse injection experiments, yielding good agreement between model prediction and experiment ( 0.90). The model enabled the prediction of RTD with variations—for example, 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 0.97. 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 NaNO3 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.

Exploration and Practice of Online–Offline Blended Teaching in Process Simulation Courses

“…Process simulation stands as one of the important cores of chemical engineering, offering users a virtual playground to explore and comprehend the complexities of real-world industrial processes. − In recent years, much attention has been paid to practical and hands-on learning experiences with these process simulation tools. − However, traditional chemical education has predominantly relied on theoretical instruction, often lacking a tangible connection to the practical applications of their studies. Process simulation can bridge this gap by immersing students in a virtual environment that mirrors the challenges and decision-making processes they will encounter in their professional careers. − This not only enhances their grasp of theoretical principles but also cultivates problem-solving skills essential for success.…”