Improved virus purification processes for vaccines and gene therapy

ABSTRACT The downstream processing of virus particles for vaccination or gene therapy is becoming a critical bottleneck as upstream titers keep improving. Moreover, the growing pressure to develop cost‐efficient processes has brought forward new downstream trains. This review aims at analyzing the state‐of‐the‐art in viral downstream purification processes, encompassing the classical unit operations and their recent developments. Emphasis is given to novel strategies for process intensification, such as continuous or semi‐continuous systems based on multicolumn technology, opening up process efficiency. Process understanding in the light of the pharmaceutical quality by design (QbD) initiative is also discussed. Finally, an outlook of the upcoming breakthrough technologies is presented. Biotechnol. Bioeng. 2015;112: 843–857. © 2015 Wiley Periodicals, Inc. Different approaches to increase process knowledge in downstream processing. Mechanistic modeling requires a deep understanding of the physicochemical property of the system, whereas a data‐driven model requires the use of statistical tools such as DoE or Monte Carlo simulations. However, the two approaches can complement each other and provide more robust process knowledge, together with the use of high throughput screening techniques, the integration of all the unit operations and the process economics parameters.