Your mission, should you decide to accept it, is to produce a COVID-19 vaccine. How do you create a vaccine that works, is safe, and can be made for the masses? You need to manufacture a safe and effective COVID-19 vaccine that can be produced at scale.
Mission accepted!
We made contact with our highly-trained scientists in their recombinant protein production lab. All to get the play-by-play on all things vaccine.
This is what we discovered. Cue the theme song.
Researchers across the globe explore thousands of different vaccine candidates every year. Each of them is designed to provide protection against a specific disease. These include influenza, meningococcal and novel coronaviruses like COVID-19. But of these candidates, very few actually make it to pharmacy shelves.
When a vaccine is in development, there are many stages. The process starts with safety testing and efficacy, clinical trials and approvals. Then it goes all the way through to the final process of commercial-scale production. Essentially, what worked in the lab must also have 'manufacturability' - meaning it can be manufactured with relative ease at minimum cost and maximum reliability. Especially in order to mass-produce the vaccine.
Scaling up a vaccine
Seems simple to scale-up vaccine production, right? Think again! Imagine recreating your family's favourite food on a commercial scale. In an extremely regulated commercial kitchen. And every meal has to be absolutely identical. Chances are there will be a lot of testing and tweaking. This process makes sure there's no compromise to flavour, look or feel.
It's a similar process for 'scaling-up' manufacturing of a vaccine. Manufacturers need to reproduce vaccines without any compromise on their safety and effectiveness. But what works in the lab requires further effort. Especially to reproduce at a large scale and the quality required to inject into people.
The low-down on scale-up
Our research scientists are specialists in vaccine protein production and purification. This takes place at our advanced biologics facility in Melbourne. The team has recently been working on the scale-up of a COVID-19 vaccine candidate. This vaccine candidate is from The University of Queensland (UQ).
We first produced the vaccine candidate at small-scale for initial testing. Now we've scaled-up a batch for the first-in-human clinical trial in Brisbane this week. The team has worked day and night. There was even a backup clinical batch running in parallel in Brisbane, just in case there were last-minute technical issues.
Commercial manufacturer CSL has now joined the team. They will optimise the methods developed by UQ, our scientists and other partners to produce the vaccine at commercial scale – with potential to make hundreds of millions of doses. To support this process, CSL scientists have collaborated with our team. They've provided knowledge and hands-on expertise to develop the vaccine product in our labs and ensure large scale manufacture is viable.
The machination of a vaccination
In the global race to produce a COVID-19 vaccine, scale-up of vaccine candidates is forging ahead. For instance, toxicology and testing phases have been underway to fast track development. These stages happen one step at a time.
But the team worked across several development stages at the same time. As a result, this shaves years off the COVID-19 vaccine development process. This is very expensive but super-fast. And in the case of a global pandemic, it's the best approach.
Step-by-step
Scientists produce the vaccine in bio-engineered mammalian cells. UQ developed these cells, which also contain the DNA codes for the antigen. The antigen is the protein that is the basis for the vaccine. From a vast pool of cells, scientists choose the best ones. They'll grow well and produce good quantities of high-quality vaccine. The development of these cells takes months, so while UQ was focusing on this, we worked with CSL to produce antigen from similar cells that had the DNA incorporated temporarily. These temporarily transformed cells are faster to produce. But they make much lower amounts of the vaccine proteins.
This approach allowed our team to develop a purification process for the antigen. They started with capturing the secreted antigen using custom resin developed by UQ. Then they followed with further chromatographic, or separation steps. As a result, this ensures the final antigen is highly purified.
Our team scaled the antigen from half a litre to 20 litres. They prepared enough highly purified antigen to test the vaccine and perform toxicity studies. This meant we were able to show the vaccine was likely to work and be safe. Even before the bio-engineered cells were available for the production run.
Making the COVID-19 vaccine
The bioengineered cells from UQ produced the antigen at levels required to move ahead with larger-scale production. The challenge for the team was to translate the process from the lab bench to the production scale. All to make enough protein for clinical use. This requires expanding the culture from hundreds of millilitres to litres. And moving it from vials to simple flasks to a state-of-the-art bioreactor. This is a challenge in itself. The key is to keep the cells growing and producing the protein. Especially in line with best practice manufacturing standards.
The antigen was then purified to the stringent requirements of a vaccine using a multi-step process. This was done at our Clayton site with practical expertise from CSL. The characterisation required to release the final product was undertaken at CSL in Parkville. We produced a large number of vaccine doses, far more than is required for the Phase I clinical trials involving 120 healthy volunteers. The remainder of the vaccines will be used for stability and other safety testing. The goal of the Phase I studies will be to assess both safety and immunogenicity of the vaccine to allow progression into larger clinical studies designed to study efficacy.
Throughout the process our team have worked hand-in-hand with the UQ team, meeting every day and exchanging the latest data in real-time. Since we had large-scale production happening in parallel, we could make adjustments and compare data as needed.
Prep the vials
Once the purified antigen passes the quality checks, it's put into vials for first-in-human clinical trials.
Building our world-class cGMP facility!
Typically, Australian biotech companies head overseas to manufacture potentially life-saving vaccines. But now we're building Australia's first collaborative worldwide accredited lab!
Our new Advanced Biologics Manufacturing Facility is forecast to open by the end of 2021. The vision is to turn vaccine and drug candidates into safe and effective biopharmaceuticals. And the manufacturing will happen at scale using industry-relevant processes.
The facility will operate using Current Good Manufacturing Practice (cGMP) enabling Australian researchers and biotech companies to progress their projects and enter overseas markets. Most importantly, it will serve as a cornerstone for the proposed establishment of an Australian vaccine pipeline. And it will be an integral part of the Australian biosafety network. For instance, it will provide the capability to produce vaccines and anti-venoms for emergencies.
The COVID-19 vaccine development is being undertaken with support from the Coalition for Epidemic Preparedness Innovations (CEPI). Additionally, this development receives funding from the Federal and Queensland governments and a large number of philanthropic donors. We rarely science alone. Moving at this speed would not be possible without the support of our broader partners including Therapeutic Innovation Australia, Cytiva (formerly GE Life Sciences), Sypharma and Patheon.
This mission will self-destruct in 5, 4, 3... but scientists will continue their hard work to find a safe COVID-19 vaccine.