Virus safety plays a critical role for complex cell and gene products, requiring specific approaches. The “Safety Tripod,” next-generation sequencing and upstream virus barriers are three such examples.
The Safety Tripod concept is an established past practice that can be adapted for innovative products. In this concept, product safety relies on (i) selecting low risk starting material, (ii) testing of raw materials and process intermediates, and (iii) implementing in-process virus clearance, i.e. inactivation/removal, steps. The latter are quantitatively the most decisive factor. This approach has been particularly successful in the past. At the same time, implementing the concept may not be as easy or even possible for virus- or cell-based therapies that depend on biologically intact virus vectors or even living cells.
[Editor's Note: Learn more about the Safety Tripod in the author's 2017 cover story, "Viral Safety Approaches for Advanced Therapy Medicinal Products."]
When it comes to testing cell substrates that are less well established than Chinese hamster ovary cells (the industry’s workhorse), one approach would be to characterize cell banks with agnostic test methods such as next generation sequencing. In particular, this approach has been shown to work for cell lines that have been found to contain viruses even after fully compendial testing.
For virus clearance, restrictions may apply for lipid enveloped and larger virus vectors for gene therapy. Non-lipid enveloped and smaller adeno-associated virus vectors, however, should still allow for standard virus inactivation methods such as solvent-detergent treatment, or removal of larger virus contaminants by nanofilters of relevant size. For larger virus vectors or cell-based therapies, however, new solutions will be necessary. Recently, upstream virus barriers have been applied as a potential alternative approach, combined with functionally closed downstream processes to avoid contamination events.
These, and other approaches to ensuring viral safety of cell- and gene-based treatments currently under development, will be discussed at the upcoming virtual Virus Forum, June 22–23. To learn more and to register, visit the event Web page.