Mitigation of viral particle interaction with glass surfaces improved Ad26 vaccine quality and long-term stability.

Therapies and vaccines based on novel modalities (e.g., viral vectors) often suffer from poor thermal stability warranting deep-frozen storage. By improving stability of these drug products (DP) at refrigerated (2-8°C) conditions, their distribution and administration could be facilitated. In this study, Adenovirus 26-based (Ad26) vaccine drug product had short-term instability at refrigerated conditions during the clinical development. This observation was investigated by a combination of conventional and innovative analytical tools, such as in situ monitoring of viral particle concentration in vials. Adsorption of viral particles to the glass vial surface was identified as main root-cause for poor stability, and this was particularly observed upon vial inversion due to the additional loss of viral particles to the previously unexposed glass surface. After the assessment of different mitigation options, standard glass vials were replaced with siliconized glass vials as they efficiently prevented viral particle adsorption on the glass surface compared to reformulation using excipients. Surprisingly, use of siliconized glass vials improved short as well as long-term stability, as Ad26 DP manufactured at commercial scale remained stable, with practically no changes of infectious titer loss, for at least 30 months at refrigerated conditions. In conclusion, the primary container selection can have a critical impact on viral vector stability. Consequently, container selection and container surface-product interactions should be assessed as part of early formulation and process development.