Quality by Design for enabling RNA platform production 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. Pfizer-BioNTech’s (BNT162b2) and Moderna’s (mRNA-1713) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the first RNA-based biologics to be approved for human use and mass produced.RNA technology holds great promise beyond infectious disease prophylaxis, from cancer and gene therapy to treatments against cardiovascular and autoimmune diseases.Current production processes have been developed and scaled up at an unprecedented speed, mostly under a Quality by Testing paradigm.Recent research has highlighted a strong link between product and process development.The application of advanced analytical and modeling technologies could rapidly reshape and digitize manufacturing processes.