We will develop, build, and operate an integrated continuous cGMP production facility for mRNA at pilot scale that will also provide a template for commercial production. This will be a platform technology that could be used across the board for mRNA production, and the project will provide significant outreach among the industry and technology transfer with the aim of reducing the barriers – technical and regulatory – to the adoption of these technologies. 

The technology will allow flexible, knowledge-based manufacturing for agile, efficient, and rapid deployment of mRNA vaccines for pandemics. If we had this technology now, we would be able to scale up rapidly and produce as much Covid-19 vaccine as needed, adapted as necessary for new variants. The significant engineering work in this project includes automation, technology/process integration, and PAT, and design, fabrication, and implementation.

The poly A tail on mRNAs makes thymine (T)-based affinity ligands a useful approach for the capture and purificationof mRNAs. Oligo-dT ligands with 20 to 60 T repeats have recently become commercially available in membrane, monolith, and particle-based chromatographic formats at laboratory scales. However, the dynamic binding capacities and corresponding through-puts of the monolith and particle-based media have not been sufficient to drive industrial bioprocessing adoption. While affinity chromatography has been shown to be amenable tocontinuous operation for protein-based biological products using various periodic continuous chromatography (PCC) systems that can also address dynamic binding capacity limitations, there are many other ways to use affinity-based interactions for truly continuous separations.