Chromatographic Purification of Viruses: State of the Art and Current Trends

Viruses and virus-derived subunits are essential components of pharmaceuticals for vaccinations as well as gene and tumor therapy. For a safe and efficient application in the public healthcare system, they must be proven to be effective and meet the regulatory requirements. The latter also concerns the product purity, relating, among others, to proteins and DNA of the host cells, which are used for virus amplification. As these contaminants may contain pathogenic and immunogenic components, their depletion is essential for a pharmaceutical application and is generally achieved by a multi-stage downstream process. In this, chromatography is an important part, flanked by various filtration or other purification techniques. In this chapter, we review the current state of chromatographic purification technologies for the downstream processing of whole active or inactivated viruses. Within this context, the focus is on technologies that are frequently applied and can be considered the standard within this application area, as well as recent developments and promising approaches in terms of platform technologies and continuous processing. Additionally, we emphasize the important choice of stationary phase backbone composition using resins, monoliths, or membranes, and give a short overview on modeling approaches to streamline process development more efficiently.