The development of effective procedures for the evaluation and validation of virus clearance in continuous/connected processes is essential for the successful implementation of these operations in biomanufacturing. The overall objective of this project was to develop an inline spiking protocol that could provide accurate quantification of virus clearance in connected / continuous bioprocessing. Experimental studies were performed with several model protein-containing feed streams using the Viresolve® Pro virus filter both with and without the Viresolve® Pro Shield H prefilter. The virus spike was added inline using a syringe pump operated at a small fraction of the feed flow rate to minimize hydrodynamic disturbances. Data were obtained over a range of spiking conditions, including the ratio of the spike to process flow rates and the duration of the spike. The residence time distribution in the system was evaluated from data for a non-interacting fluorescent tracer added to the inline spike. The viral clearance evaluated using Phi X174 and MVM as model viruses were in excellent agreement with data obtained in a conventional batch process, demonstrating the reliability of the inline spiking protocol. These results provide a framework that can be used for the design and optimization of inline spiking protocols to evaluate virus clearance in continuous/connected processes.

Development of an in-line spiking system for evaluation of viral clearance in continuous / connected bioprocesses

ACS Spring 2022

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