Could Australia have its own mRNA vaccine production operation soon? Victoria has announced $50 million in funding for it, while international biotech company BioCina said they have the capability in SA with federal government support. But questions remain about the timelines and feasibility of getting up to speed.
Australia had a lot riding on the Oxford-AstraZeneca vaccine, 50 million doses of which are being manufactured on-shore at CSL in Melbourne.
If we’re churning out AstraZeneca vaccines so quickly, why can’t we switch over to an mRNA vaccine like Pfizer’s or Moderna’s?
“mRNA vaccines are completely new class of vaccine,” says Anton Middelberg, professor of chemical and biomolecular engineering at Adelaide University. “And as a result, we’re having to look at a completely different manufacturing scale.”
Until 2021, approved vaccines have contained at least part of the virus they’re targeting to work. The Oxford-AstraZeneca vaccine, for instance, contains DNA for spike proteins from SARS-CoV-2 to trigger the immune system.
But for mRNA vaccines like Pfizer and Moderna, “the starting point is that you don’t need the virus culture. You do not need the virus in the manufacturing process,” says Middelberg.
“So that actually changes completely the production paradigm.”
Australia has a long and hallowed history of viral cultivation – particularly in Victoria, where Nobel laureate Frank Burnet established the techniques for growing a virus using eggs. Now, CSL is using mammalian cells to develop the components of the AstraZeneca vaccine.
Viral vector vs mRNA vaccines
- Vector virus (like adenovirus) is grown in mammalian cells
- Vector virus is purified from cells
- Parts of target virus are added, turning the vector into a vaccine
- Vaccine is tested and quality controlled
- Microbial cells are used to make enzymes & plasmid DNA
- Those ingredients are reacted with each other to make mRNA
- mRNA is coated by adding polymers and lipids
- Vaccine is tested and quality controlled
“Given the expertise base we have in Australia… it makes sense that as a nation we would have chosen to go down the AstraZeneca pathway,” says Middelberg.
The mRNA production pathway is different. Microbial cells are used to make plasmid DNA and enzymes, which are reacted together to create the mRNA that enters the body. This mRNA is then coated with polymers and lipids so it can remain stable as it does its work.
“With mRNA, a lot more of it happens without cells being present.” The only part of the process that requires cells is the production of plasmid DNA and enzymes, and the cells required are microbial cells – not our well-established mammalian cells.
“These are quite different to mammalian cells. They are widely considered an industrial organ, and they’re used to make things at scale, for example enzymes used in detergents,” says Middelberg.
“They don’t rely on those historical approaches and knowledge of virus culture that’s underpinned vaccine production for a very long time. And it turns out the biotech industry has a history that’s quite relevant.”
So we need microbial cells, but over the past few decades mammalian cells have been providing therapeutic wins. This means that both globally, and nationally, there’s a dearth of expertise in microbial cell culture.
“The most advanced facility for microbial culture is actually one in Adelaide,” says Middelberg. The BioCina manufacturing plant in Thebarton, SA, is a spinoff from the University of Adelaide (where Middelberg is deputy vice chancellor). Right now, it’s the only facility in the country with regulatory approval for microbial culture.
According to Ian Wisenberg, CEO of BioCina, once the plasmid-making is developed using their microbial expertise, the rest of the vaccine manufacture is fairly straightforward. The plasmid development at Thebarton will take about six months, for a couple of reasons. “One is obviously developing that process internally, but also having the equipment to scale. We just placed an order for a 300 litre bioreactor specifically for the plasmid processing,” says Wisenberg.
Once the plasmids and the enzymes are in place, the mRNA production and the lipid coating will be simple to do at the plant – the next roadblock is bottling the vaccines, or ‘fill/finish’. This is the final step of the manufacturing process, involving getting the vaccines into vials, and – like the rest of the process – needs to be sterile and efficient.
“We can do all the manufacturing. It’s that fill/finish part that we don’t have any ability or capability around,” says Wisenberg.
“It would be necessary for some other commercial enterprise or the government to step in and set that up.”
But this is a question of money and will, rather than capability. “There are several facilities that are within walking distance of our Thebarton plant that might make sense,” says Wisenberg.
What will be the price tag to reconfigure the lab? To do it quickly, dropping a preconfigured lab into the space, “about $20 million,” says Wisenberg. “That’s not necessarily our plan, but that is an option…it would certainly put all the pieces in place in 6-12 months.” Wisenberg hopes to expand and extend the plant to other mRNA products as well, which is going to take more time and money.
And then for a fill/finish facility? “For that size, probably also in the $15 to $20 million range.”
Middelberg says that large-scale mRNA vaccine production in Australia could be happening in 6-12 months, if a few things went right: the BioCina facility would need to be reconfigured, and would need access to licensed technology from Pfizer, Moderna or another mRNA vaccine producer.
“They could deliver, within that timeframe, about 100 million doses,” he says.
Whether or not we’re we making mRNA vaccines for COVID-19 by 2022, the technology is worth investing in.
“I think this is a great opportunity for Australia to essentially have sovereignty over its supply of vaccines for now and for the future, because we’re going to need boosters and we’re going to potentially have another pandemic,” says Wisenberg.
“We believe mRNA is going to be the platform of the future, because it’s very, very easy to change the code and develop a new vaccine.”