International biotechnology company Moderna will establish an mRNA manufacturing facility in Melbourne, after striking a deal with the Federal and Victorian governments.
The facility aims to produce mRNA vaccines by 2024, “pending regulatory and planning approval”. These vaccines could be used for COVID, influenza, and future pandemics – among other diseases. During a pandemic, the facility could make 100 million mRNA vaccines per year.
The Australian government has been seeking interest from biotechnology companies on mRNA manufacture since May, when ATAGI recommended against the AstraZeneca vaccine for some age groups, placing a strain on the mRNA supply.
Given the long consultation period, and the fact that Pfizer and Moderna created test vaccines in a matter of weeks after the outbreak of SARS-CoV-2, why is it going to take so long to make these vaccines onshore?
The key is making mRNA – or more specifically, making the plasmid DNA and enzymes which are required to make mRNA.
This process requires fermenting in microbial (or bacterial) cells, and most Australian biotechnology facilities don’t have the right equipment or skillset for microbial fermentation. CSL, for instance, which has been making the AstraZeneca vaccine in Melbourne, specialises in mammalian cell culture.
At present, there is only one facility in the country with the regulatory approvals to make pharmaceutical-grade mRNA precursors – the BioCina plant in Adelaide. BioCina intends to make these precursors by next year, but lacks the other infrastructure to make mRNA vaccines.
To set up such a facility will require a large investment in technology and training.
“Vaccine production involves a complex range of steps that require not only significant up-front investment in R&D, but also in selecting suppliers of key ingredients, setting up manufacturing processes and quality checks, and sourcing primary and secondary packaging,” says Dr Vinod Balasubramaniam, a virologist at Monash University in Malaysia.
“There’s a ton of equipment involved in our manufacturing,” says Ian Wisenberg, CEO of BioCina.
“There’s upstream, midstream and downstream equipment.”
In addition to the fermentation, a facility would need to be able to prepare the right compounds for fermenting – a process that takes several specialised staff and equipment – as well as refolding, isolating and purifying the products after fermentation.
Once the mRNA is made, it then needs to be encapsulated in lipids to keep stable – known as lipid nanoparticle coating – and then bottled for distribution in a fill/finish facility. While the mRNA capability doesn’t currently exist in Melbourne and will need to be set up by Moderna, Victorian researchers have successfully demonstrated the second two parts of the vaccine manufacturing process.
As well as these requirements, the facility will need to be Good Manufacturing Process Certified by the Therapeutic Goods Administration. If the mRNA vaccines are sold overseas, they will also need to be certified by other countries’ bodies – such as the US’ Federal Drug Administration or the EU’s European Medicines Agency.
“To get those approvals, you actually have to go through the process of manufacturing a product that goes through to commercial,” explains Ian Wisenberg, CEO of BioCina.
“The US FDA will come and actually physically inspect the facility to make sure that it complies with all their requirements. And many of the agencies around the world will accept the US FDA’s recommendations to approve.”
This approval process can also take months – or even years. Every step of the manufacturing process needs to be meticulously clean, with no foreign or unexpected matter entering at any point in the stream.
While its fruits are still several years away, this deal with Moderna will be a useful boon to Australia’s nascent mRNA industry.
“The best news about this is that Moderna will engage much more heavily with the research community here. This is a welcome addition to the already burgeoning RNA ecosystem across Australia which has strength across the whole RNA field, not just mRNA vaccines,” says Pall Thordarson, director of the UNSW RNA Institute.
“It will make a huge difference in developing other RNA technology that will transform our health outcomes over the next 10 to 20 years.”