Proceedings of the 2017 Viral Clearance Symposium, Session 2.2: DSP Unit Operations-Purification Unit Operations

The process capability and potential for various forms of chromatography to remove viruses have been discussed extensively in the literature, including the observed variability in performance of some unit operations such as Protein A and cation exchange (CEX). Some unit operations such as anion exchange (AEX) have shown robustness over a wide range of operating conditions. The robustness and effectiveness of the AEX step combined with a detailed understanding of the mechanisms that result in virus and impurity partitioning versus protein partitioning (e.g. conductivity, loading, pH range) support the feasibility of a generic or modular claim for AEX. A more fundamental understanding of the mechanisms for other chromatographic media (Protein A, CEX, and mixed-mode) could lead to more effective and more robust log reduction value (LRV) claims for these steps as well. Specific examples of CEX and mixed-mode chromatography were explored in the session and were also discussed in detail at the 2013 and 2015 Viral Clearance Symposia. Although some gaps remain in the mechanistic understanding of these unit operations, significant progress has been made and was reported at the 2017 Viral Clearance Symposium. It is important to note that recent publications on the mechanisms of viral clearance for mixed-mode chromatography and a framework for measurement of relative hydrophobicity have provided insights and new tools to better define the operating space and critical process parameters. The session also explored the use of next-generation mixed-mode adsorbers and the potential mechanisms contributing to the observed viral clearance. Gaps were also identified (e.g. integrity test when size-based mechanisms are used) and should be addressed to ensure robust viral clearance for these integrated and productive emerging unit operations.LAY ABSTRACT: Preparative chromatography is the most widely used unit operation for purification of therapeutic proteins. This session focused on the potential for various forms of chromatography to remove viruses. To advance to the next level of process, understanding the virus removal mechanism of different types of chromatography was addressed.