In vivo gene therapies have shown benefit in treating and potentially curing life-threatening diseases. Recombinant adeno-associated viruses (rAAVs) have become the most widely used delivery system for administering in vivo gene therapies.
Yet, while there are many therapeutic products in development, only a small number of gene therapy products are currently approved and concerns have recently been raised about the safety of high doses when administering rAAV. Other ongoing issues include a lack of formal regulatory guidance or recommendations on an acceptable level of the impurities associated with unwanted rAAV capsid products.
To address these gaps and establish an industry position, the BioPhorum Cell & Gene Therapy Empty, Full and Partially Filled Capsids sub-team conducted an industry-wide benchmarking survey.
The results have now been published in this paper, which sets the stage for a comprehensive exploration of the current practices, methodologies, and emerging technologies as they apply to rAAV vectors.
The paper brings a host of benefits for readers. The survey has allowed commentary on the analytical methods used for the release and/or characterization of full, partially filled, and empty capsids in various process development steps. Also, the discussion of the results clarifies which analytical methods are amenable to GMP validation for product release in late-stage clinical trials and commercialization of gene therapy products.
The paper also addresses the lack of shared industry standards for reliable empty/full capsid quantitation during process development or GMP release and the incomplete understanding of the impact of partially filled capsids.