summit - sustainable manufacture of macromolecular intracellular therapeutics

This project will develop a flexible and scalable RNA-manufacturing process and delivery system for the sustainable manufacture of biologic drugs, with considerably reduced material-use/energy-costs and the need for repurposing or rebuilding facilities. RNA is the medicine platform of the future with many application-types in clinical trial. RNA therapeutics are suitable for manufacture without using cell-based processes, so it is possible to take an RNA sequence to a candidate vaccine or therapeutic in weeks. A particular advantage is that same manufacturing plant can be used to produce an extraordinary array of drugs from personalised medicines to vaccines. The aim of this application is to further enhance the RNA-manufacturing process to reduce waste and improve sustainability. We will achieve this through several RNA-manufacturing innovations. We will optimise a scalable RNA Biofoundry (that we call Biofoundry in a box --BiaB). This will enable globally distributed-manufacturing via continuous-flow processes, to improve RNA purity and reduce waste. We will also develop tunable and thermostable formulations; these reduce cold-chain requirements and the need for energy-consuming ultralow temperature freezers. Alongside the equipment, novel excipients will be developed for a supramolecular _delivery system_ _that does not require organic solvents_ for sustainable manufacture of local, disease-strain-specific therapeutic/vaccine applications. We will also develop a low-loss fill-finish line so that all of the process intensification advantages of the RNA Biofoundary to produce a minimum viable product size for early clinical development are not wasted through the traditional approaches to demonstrating quality and sterility assurance. Whilst we anticipate that RNA can be used for a wide range of indications, the immediate use case is as a vaccine. Humanity has never been at greater risk of zoonotic-pathogen outbreaks, recent high-profile examples include zoonotic viral pathogens (SARS/MERS/Ebola/Influenza/monkeypox). The COVID-19 pandemic demonstrated the capacity for rapid development, high efficacy and positive safety profile of mRNA vaccines as needs arise. The focus of this application therefore will be to optimise the sustainability of facility capable of manufacturing a pipeline of RNA vaccines to prevent a potential avian-influenza crossover-event before it becomes a pandemic. Improved pathogen surveillance and sequencing will enable infectious diseases to be identified and therapeutics designed earlier (e.g. the CEPI 100-day mission). The scale of the manufacture we are proposing, combined with the thermostability makes our approach highly suitable for use in low-and-middle-income countries (LMICs), where there is a vaccination backlog.