Abstract
The process capability and potential for various forms of chromatography to remove viruses has been discussed in the literature extensively including the observed variability in performance of some unit operations such as protein A and CEX (Miesegaes 2010A, Miesegaes 2010B, Roush 2015). Some unit operations such as AEX have demonstrated robustness over a wide range of operating conditions (Miesegaes 2010B, Roush 2014). The robustness and effectiveness of the AEX step combined with a detailed understanding of the mechanisms that result in virus and impurity partitioning vs. protein partitioning (e.g. conductivity, loading, pH range, etc.) 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 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 (Hubbard and Roush, 2014; Chen, 2016; Gallo, 2016). 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 Symposia. It is important to note that recent literature publications on mechanisms of viral clearance for mixed mode chromatography (Brown et al Biotech Bioeng, 2017) and a framework for measurement of relative hydrophobicity (Johnson et al J. Chrom B, 2017) 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 employed) that should be addressed to ensure robust viral clearance for these integrated and productive emerging unit operations.
- Affinity chromatography
- Downstream processing
- Ion exchange chromatography
- Membrane adsorbers
- Multimodal chromatography
- Viral Clearance
- Received June 18, 2018.
- Accepted June 28, 2018.
- Copyright © 2018, Parenteral Drug Association
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