Professor Harris Makatsoris from King’s College London for developing a ‘factory-in-a-box’ that allows the rapid manufacture of synthetic RNA vaccines against the SARS-CoV-2 virus and minimises the space required for high-volume vaccine production. ©thisisjude.uk 2020

Intro paragraph

The race is on to develop a vaccine to protect us against COVID-19 and engineers are playing a central role. Professor Harris Makatsoris developed a ‘factory-in-a-box’ that not only minimises the footprint requirements of production space traditionally needed for high volume vaccine manufacturing but also makes it possible to prepare vaccines locally, at the point of use.

Engineering contribution

The Sars-CoV-2 virus (which causes COVID-19) and other emerging threats require rapid response platforms to ensure new vaccines can be rolled out. A major obstacle to the development and deployment of suitable candidate substances is manufacturing them at the scale required during each phase of the development, from clinical trials to large-scale production.

To overcome this, Harris Makatsoris, Professor of Sustainable Manufacturing Systems at King's College London, has come up with a novel process intensification technology for vaccine production, to help scale up production of the COVID-19 vaccine substances discovered by his fellow scientists. His innovative ‘factory-in-a-box’ solution enables vaccines to be manufactured quickly where they are needed, such as in hospitals.

Exploiting flow technologies, Professor Makatsoris designed a system of ‘pluggable fluidic device modules’ that can perform in-vitro transcription (IVT) to produce synthetic, self-amplifying RNA-based vaccines (saRNA). RNA-based vaccines work by introducing a tiny part of the genetic code of a virus into the body, containing the instructions cells need to produce antigens to the virus when they are exposed to it during a disease outbreak.

The ‘factory-in-a-box’ is pre-loaded with the enzymes, nucleotides and other reagents needed to trigger the IVT process. It enables the preparation of synthetic RNA vaccines in tightly controlled process conditions from plasmid DNA comprising the genes in the correct sequence.

A single installation of the ‘factory-in-a-box’ can produce up to 600 doses per minute and multiple devices could also operate in parallel to rapidly and reliably manufacture enough vaccine to meet local or national demand.

Impact

As the technology combines preparation, synthesis and downstream filtration operations with computer monitoring and control in an isolated system, it can operate safely in less restricted environments. This makes it equally useful in a local setting such as a hospital or in a conventional pharmaceutical manufacturing facility. It is rapidly deployable, offering end-to-end manufacturing capability to satisfy national or international needs, minimising dependence on overseas supply chains.

Facilitating on-demand production of synthetic RNA against SARS-CoV-2 is an amazing achievement and incredibly helpful to researchers, because self-amplifying RNA-based vaccines are preferred over other approaches as they are produced cell-free and have higher efficacy. The work has been conducted in close collaboration with Imperial College London St Mary’s, one of the key centres working on a vaccine against the pathogen, funded by the Department of Health and the Engineering and Physical Sciences Research Council. In addition to addressing the current pandemic challenge, the technology can be applied to other vaccine platforms and other types of gene therapy.

Professor Nilay Shah FREng, Professor of Process Systems Engineering at Imperial College London, says: “As the pharmaceutical industry is now gradually transitioning to the adoption of process intensification technologies for the next generation drug manufacture, Harris’ work is an ideal exemplar and indeed a demonstration of the capability, especially in emergency situations. This work shows how engineering practice, management skill and innovation can create solutions to respond rapidly to emergencies and challenges such as the current pandemic and ultimately deliver against society’s most urgent need