Formaldehyde is the most widely used chemical agent to inactivate virus propagated for vaccine manufacturing. The mechanism of inactivation is by irreversibly cross-linking primary amine groups of viral surface proteins with proximal nitrogen groups, which include those of nucleic acids or proteins from both viral and non-viral sources. According to the Ph. Eur (2011c), the concentration of formaldehyde cannot exceed 0.1% (v/v) at any time during the inactivation procedure. Procedures vary for formaldehyde inactivated vaccines, primarily focusing on formaldehyde concentrations, incubation temperatures and time. Higher formaldehyde concentrations and higher temperatures may expedite the inactivation process but may also negatively impact the immunogenicity of the viral antigens and ablate in-process analytics. Therefore, it is important to determine the effect of formaldehyde concentration and prolonged incubation time as well as the contribution of the thermal component in destroying infectivity of the virus without adversely impacting the infectivity and hemagglutinin titer of virus and in-process analytics. The objective of this study was to characterize the design space around influenza virus inactivation using Design of Experiments (DOE) and recommend optimal process parameters that retain integrity of the virus and process analytics for large scale virus inactivation.<br/><br/>

Leveraging design of experiments to characterize the effects of formaldehyde concentration, incubation temperature and time on influenza A/WS/33 (H1N1) inactivation and process analytics

251st National Meeting (2016)

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