(340bg) Advancing Downstream Processes for the Purification of Therapeutic Viruses | AIChE

(340bg) Advancing Downstream Processes for the Purification of Therapeutic Viruses


Kawka, K. - Presenter, McMaster University
Ghosh, R., McMaster University
Latulippe, D., McMaster University
Research Interests

Viruses are an important new class of biotherapeutics that have been gaining significant interest for their applications as vectors in gene therapy and vaccines and as oncolytic agents in novel cancer immunotherapies. While these new therapies present great promise in clinical trials, the large-scale purification of viruses is still hindered by low overall yields that are typically below 20%. Therefore, there is a clear need for more effective downstream technologies especially suited for the purification of each type of virus.

Virus purification processes involve a series of interconnected unit operations, and it is a challenge to select the optimal conditions for each step. While most of our studies involve applying membrane chromatography (MC) as a method to remove host-cell impurities (i.e. DNA and proteins), it is important to simultaneously consider additional process steps. This was demonstrated in a study where we applied an integrated approach evaluating the effect of an enzymatic DNA digestion step on the performance of the MC for host-cell DNA removal in an adenovirus purification process. After a series of optimizations, an 80-fold improvement in the removal of DNA and a 10-fold scale-up in the amount of processed virus were achieved,a compared with an initial round of optimizations that considered the MC step alone.b

The physicochemical characteristics of different types of viruses also impose a challenge for process development, making it impossible to develop a global process that would be effective for all virus types. For example, while anion-exchange membrane chromatography was a great option for the purification of adenoviruses, it was not successful for the purification of rhabdoviruses. Instead, hydrophobic interaction membrane chromatography (HIMC) was much more suitable for the latter. Therefore, we have developed a process where rhabdoviruses were harvested from culture media, concentrated more than 30-fold, and successfully purified during a one-step HIMC process.

This collection of experimental results along with literature data are currently being used in an assessment of the economic feasibility of virus production processes. Upstream and downstream operations were modelled using the software BioSolve Process (Biopharm Services). Several production scenarios are presently being analysed to identify key cost drivers and to quantify their contribution to the cost of goods of virus production across a range of scales. Considering practical limitations in a comprehensive analysis of the economic aspects of virus manufacturing will help us address critically outstanding questions in the field and will guide a more rational selection of process conditions. Ultimately, these advances will benefit patients that will be able to rely on new, safe, and affordable biotherapeutics.


a Kawka, K., et al. "Integrated development of enzymatic DNA digestion and membrane chromatography processes for the purification of therapeutic adenoviruses." Separation and Purification Technology 254 (2021): 117503.

b Kawka, K., et al. "Purification of therapeutic adenoviruses using laterally-fed membrane chromatography." Journal of Membrane Science 579 (2019): 351-358.


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