Implementation and Characterization of Solvent Detergent Viral Inactivation in Single Use Bags

Biomanufacturing of recombinant products from mammalian cell culture systems and plasma derived products requires at least two orthogonal virus reduction steps to comply with regulatory pathogen safety risk mitigation guidelines. Solvent detergent viral inactivation (SD VI) has historically been effectively utilized for the inactivation of lipid-enveloped viruses from plasma derived products, yet only recently have process development activities focused on implementation of SD VI in single use systems.  The adoption of single-use technologies for bioproduction continues to progress, driven predominantly by the benefits of operational flexibility, speed of implementation, lower capital investment, and elimination of cross contamination concerns.  However, the suitability of this flexible production platform for SD VI remains to be fully characterized.  This presentation will review data generated from a recently completed SD VI study on a single-use mixing platform that demonstrates successful performance of this operation in a flexible manufacturing environment.  Specifically, chemical compatibility, non-specific chemical adsorption, and leachables profiles of the reagents used in SD VI with the container film, mixer components, and transfer assemblies will be reviewed.  In addition, the effectiveness of SD VI in single-use bags, based on small scale virus spiking studies, will be presented.  Best practices guidance for appropriate unit operation set up, connectology, mixing and operation from 50 to 500L scale will also be reviewed.  Finally, the potential regulatory impact of the implementation of single-use technology on solvent/detergent viral inactivation, based on the observations from this study, will be discussed.