The development of a scalable, robust, and economically viable process that provides high-quality mRNA requires careful consideration of the manufacturing steps, including the definition of relevant in-process controls and critical quality attributes. It starts with the mRNA sequence of the template impacting not only the development process, but also the quality system, supply chain, equipment, raw materials, and consumables.
A Design of Experiments (DoE) approach is also critical to optimize the process parameters and ensure robustness of the entire process. This includes optimizing the robustness of the upstream process, including the IVT reaction, polyadenylation, and capping, to reduce by-products and impurities formation which have an impact on the downstream complexity. The downstream process should be adaptable and flexible, with the intrinsic physicochemical characteristics of a specific mRNA construct defining the selection of the most appropriate approach.
Examine why template sequence characteristics are relevant for cGMP manufacturing of high-quality mRNA and consider insights on how to develop a scalable, robust, and economically viable process.