Vaccine production platform technologies have played a crucial role in rapidly developing and manufacturing vaccines during the COVID-19 pandemic. The role of disease agnostic platform technologies, such as the adenovirus-vectored (AVV), messenger RNA (mRNA), and the newer self-amplifying RNA (saRNA) vaccine platforms is expected to further increase in the future. Here we present modelling tools that can be used to aid the rapid development and mass-production of vaccines produced with these platform technologies. The impact of key design and operational uncertainties on the productivity and cost performance of these vaccine platforms is evaluated using techno-economic modelling and variance-based global sensitivity analysis. Furthermore, the use of the quality by digital design framework and techno-economic modelling for supporting the rapid development and improving the performance of these vaccine production technologies is also illustrated.

The COVID-19 crisis has highlighted the critical role of vaccine manufacturing in managing infectious disease outbreaks and pandemics. Enhancing RNA manufacturing capability, distribution and flexibility will now be central in future epidemic preparedness and emergency response strategies. This insight showcases the adaptation of Quality by Design (QbD) principles to RNA vaccine platform production processes. In particular, the implementation of a digital, holistic, and RNA-specific QbD approach can revolutionize vaccine development, regulatory approval, and manufacturing. We discuss how this framework can help overcome the remaining scientific, industrial, and regulatory challenges, potentially leading to a globally distributed network of versatile and pre-approved manufacturing platforms. A new blueprint is herein proposed for the development, validation and lifecycle management of these platform processes.

RNA-based products have emerged as one of the most promising and strategic technologies for global vaccination, infectious disease control, and future therapy development. The assessment of critical quality attributes (CQAs), product-process interactions, relevant process analytical technologies, and process modeling capabilities can feed into a robust Quality by Design (QbD) framework for future development, design, and control of manufacturing processes. QbD implementation will help the RNA technology reach its full potential and will be central to the development, pre-qualification, and regulatory approval of rapid response, disease-agnostic RNA platform production processes.