Continuous downstream processing has the potential to transform the manufacture of biotherapeutic products through improvements to the efficiency, cost, and quality of these processes. Significant effort has been made in both academic and industry settings to adapt batch unit operations to their continuous counterparts, with the bulk of the work focused on the challenging task of developing continuous chromatography platforms. As a flow-through operation, virus filtration seems easily adaptable to the continuous process paradigm, and as such, it has received little attention from researchers thus far. However, implementing virus filtration into a fully integrated continuous downstream process has significant challenges which will need to be addressed. For instance, the output of a continuous chromatography step is a series of elution peaks with constantly changing concentrations of protein, salts, and impurities. The impact of such a dynamic system on a filtration process is not yet understood and may require engineering solutions to mitigate its effects. Another difficulty will be validation of these critical viral clearance steps. Typical batch spiking studies, which have been traditionally used for viral clearance validation, may not be suitable for these highly dynamic systems. Although in-line spiking and other validation strategies have been proposed, the feasibility and acceptance of these approaches is not fully understood. This presentation will discuss basic considerations in designing a virus filter unit operation for integration into a continuous downstream purification process, as well as some of the challenges which must still be overcome.

Challenges of implementing virus filtration into continuous manufacturing processes

255th National Meeting (2018)

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