The Importance of Viral Clearance and Characterization in Gene Therapy Products
Speakers:
- Ya-Chen Chang, Regenxbio
- Akunna Iheanacho, Texcell
- Katelyn Pritchard, Texcell
- Maja Leskovec, BIA Separations, Inc.
Maja Leskovec, Head of Process Development Viruses at BIA Separations, Inc., presented “High Resolution Chromatography for AAV Polishing as key Virus Removal Step” as part of the webinar “The Importance of Viral Clearance and Characterization in Gene Therapy Products”.
The Importance of Viral Clearance and Characterization in Gene Therapy Products
It is a regulatory requirement (ICH Q5A Revision 2) to demonstrate viral safety of biotechnology product derived from in vitro cell culture, including viral-vector derived products like recombinant Adeno-Associated virus used as a delivery medium for gene therapy products. Viral clearance in gene therapy product poses different challenges from the other non-viral biotechnology product in the viral removal strategies. In this webinar, we will present a case study with a clinically relevant AAV8 downstream process:
- The rationale of the study design: the choices of virus panel, surrogate and the unit operation for demonstrating viral clearance.
- Present the clearance achieved in a scaled down model of the process.
High Resolution Chromatography for AAV Polishing as key Virus Removal Step
Viral vectors undergo regulatory requirements for viral safety (ICH Q5A Revision 2), similar to any other product derived from human or animal cell line culture. One of the widely used vectors in gene therapy is the Adeno-associated virus, with currently more than 350 ongoing clinical trials. Similar characteristics of full AAV vector and potentially adventitious virus contaminants represent a unique challenge for efficient virus removal strategy, very similar to ensuring efficient separation of empty and partial particles, co-produced during the upstream process.
Such separation requires very high-resolution chromatography media and scale-to-scale reproducibility within just a few percent. To address the above-mentioned needs BIA Separations, Inc. developed new CIMmultus HR line (HR stands for High Reproducibility) columns with better resolution and narrower acceptance criteria. These columns allow for batch-to-batch and scale-to-scale reproducibility within just 3% of the AAV8 empty capsid isoconductivity elution and permit step gradient elution using the same buffer strength at any scale. Removal of empty capsids in two orders of magnitude should be possible at any scale, as well as efficient several log removals of model viruses.