Continuous bioprocessing is rapidly gaining momentum, and will be implemented in more manufacturing processes in the next few years. The process intensification produced creates benefits of operational flexibility and efficiency, reduced facility footprint and capital expenditure, and significant cost of goods savings. A fully continuous bioprocess from end to end enables greater utilization of all unit operations, which share all these benefits. Breaking that chain during virus filtration to allow semi-batch operation risks losing some of the advantages of continuous operation throughout the process. This can also lead to a complicated filtration process with either an excessive number of small virus filters or large holding tanks surrounding the virus filter. Continuous virus filtration also generates risks by driving operation to low flows and pressures and increasing the risk of process interruptions. We look into the detailed technical drivers and governing equations behind the risk of low pressure operation and process interruptions, looking at the balance between convective forces and hindered diffusion of viruses. The solution lies in the newest generation of virus filters which are ready for continuous processing due to unique pore structures and high permeabilities. We demonstrate the ability of PegasusTM Prime to deliver strong retention at operating pressures as low as 70 mbar (1 psi) for several days of operation. We also present methods which resolve practical problems relating to process scale continuous virus filtration and the challenges of virus validation. The addition of practical solutions to the technical advances in virus filter design help to facilitate robust continuous virus filtration. This then contributes towards the future of continuous processing by maintaining the benefits provided by the enabling technologies that have advanced continuous bioprocessing from potential theory to economical practice.

Technical and practical solutions to the challenges of low pressures and process interruptions in optimal continuous virus filtration

255th National Meeting (2018)

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