(204b) Industrial/Academic Partnerships - Mechanistic Understanding of Eco-Friendly Surfactants for Virus Inactivation

Industry and academia have unique roles to play in developing new methods to manufacture biological therapies. Industry brings products to market to save lives, whereas academia has a key role to train and educate the next generation of scientists and engineers. But in the process of training and educating, industry can be a vital source of information on key problems that are encountered and resources. One example of such a partnership is the need to improve viral clearance. Virus clearance is crucial and required to produce biopharmaceutical products, thus avoiding iatrogenic transmission of pathogenic viruses. For a long time, Triton X-100 has been a gold standard for virus clearance in detergent-mediated virus inactivation. Due to toxic byproduct formation created in the breakdown of Triton X-100 in aquatic environments, the EU has mandated its replacement in all biopharmaceutical manufacturing processes. Therefore, we are testing two classes of eco-friendly surfactants, non-ionic glucosides, and zwitterionic amine oxides, and comparing their virus inactivation to Triton X-100. Tetradecyl amine oxide and nonyl glucoside at 1X critical micelle concentration (CMC) were found to be promising alternatives for virus inactivation. The Suid herpesvirus (SuHV-1) and herpes simplex virus (HSV-1) were inactivated within a minute of surfactant treatment. But above and beyond screening for virus inactivation, we are pursuing the mechanism of inactivation. Depending on the type of surfactant and the model virus, detergent-mediated inactivation occurred by either removing the envelope, with no effect on the envelope, or by rupturing of the envelope of the virus. Knowledge gained here with the concentration, duration, and mechanism of virus inactivation for surfactants will provide valuable insight into the design and optimization of detergent-mediated virus clearance strategies in industrial antibody applications.