Advancing regulatory dialogue: In silico models for improved vaccine biomanufacturing - an expert meeting report.

On March 30, 2022, Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), organised a hybrid workshop, titled "Regulatory Dialogue for Road Maps of Implementation of New Tools in Chemistry, Manufacturing, and Controls Dossiers." This event brought together modellers, regulatory experts, and academic and industry professionals specialising in vaccine process and product development. The sessions discussed key parameters and requirements for model development and verification relevant to vaccine biomanufacturing and shelf life. The stability model was highlighted as having the most significant impact on the common technical document (CTD) due to its potential to streamline data requirements. Regulators are open to considering reliable reduced stability data packages (3-12 months) instead of the standard 36 months, potentially expediting product availability. Appropriate study design reduces uncertainty and therefore the risk of making poor decisions. Upstream models are further from the final product, and their role in the control strategy of the product will define their level of risk and, therefore, requirements for validation and inclusion of information in the file. Regulators may consider downstream models high risk as these can be associated with the monitoring and/or control of critical quality attributes and/or be involved in the release of a product. However, requirements for validation and/or dossier content should always be linked to the intended use of the model and its overall role in the control strategy as per the new EMA Quality Innovation Group Considerations regarding Pharmaceutical Process Models. The success of these models hinges on manufacturers providing enough quality data to prove their accuracy in representing real-world processes. Proactive engagement with regulators, supported by detailed evidence, can foster regulator understanding of new models and potentially lead to new guidelines and pathways for model acceptance.