We’ve learnt a lot of new acronyms in the past 18 months. First, the World Health Organisation (WHO) named the coronavirus disease (COVID-19) and recommended we use personal protective equipment (PPE). Then came vaccines like Pfizer and Moderna, which feature messenger ribonucleic acid (mRNA) encased in lipid nanoparticles (LNPs).
In a time of abbreviations and scientific acceleration, then, it’s good to know some corners simply can’t be cut. The safety of COVID-19 vaccines is being ensured by rigorous procedures set by regulatory authorities around the world – from the Food and Drug Administration (FDA) in the US, to the European Medicine Agency (EMA) in the EU, and the Therapeutic Goods Administration (TGA) in Australia.
But what do these processes involve, exactly? And what does it take to get a vaccine to market? To find out we spoke with La Trobe alumna Dr Rosalie Cull (PhD in Biochemistry, 1998), who’s helping Moderna bring their new COVID-19 mRNA vaccine to Australia.
From PhD to biotech leader
Rosalie has always been passionate about turning scientific research into marketable products. Throughout her 30-year career in the biotech and pharmaceutical industries, she’s brought a range of therapeutic products to market, including medical devices, cutting edge oncology drugs and orphan drugs for rare diseases.
When she came to study her PhD in biochemistry at La Trobe University, Rosalie had already worked in biotech companies for several years. Her industry experience gave her a different perspective to some of the other students in the lab.
“For me, it was never about pure research. It was about asking, ‘What is the commercial imperative? What does the product look like at the end of the day?’” Rosalie says.
Her decision to focus on biotech commercialisation was later cemented when, as then-president of La Trobe’s Postgraduate Students’ Association, she was invited to sit on a range of committees. One of those committees oversaw the start-up of the University’s Research and Innovation Precinct.
“Through these committees, I was able to engage with a range of different business aspects. I spoke to a lot of people about careers that were related to science, to see what was going to suit me,” she says.
“At that point I knew I wasn’t going to go back into the lab when I finished my PhD. I wanted to do something different and regulatory affairs seemed to be the thing – though I did a lot of work in business development and commercialisation, as well.”
In her current role as CEO of Adjutor Healthcare, Rosalie helps biotechnology, medical and pharmaceutical companies navigate the complex pathways to regulatory approval, registration and commercialisation in Australia and New Zealand, into Asia and across North America and Europe.
Last year her team worked with local importers and manufacturers to secure TGA approval for the PPE, disinfectants, syringes and needles that supplied Australia’s National Medical Stockpile. They also helped local companies comply with WHO hand sanitiser requirements.
Now, Rosalie and her staff are managing the regulatory submission and approval process for Moderna, whose COVID-19 vaccine is the second mRNA vaccine to be purchased by the Australian Government.
Approving a COVID-19 vaccine for use
Before any vaccine can be used in Australia, the TGA needs to assess its safety, efficacy and quality. Ultimately, a vaccine can only be registered for use if its benefits are much greater than its risks. It’s up to Rosalie and her team to make sure the TGA has all the information it needs to properly assess whether Moderna’s COVID-19 vaccine meets the required standards.
For COVID-19 vaccines, and some other products, the TGA offers what’s called a provisional approval pathway. This provisional approval process allows temporary registration of promising new products, where the benefits of early access substantially outweigh the risks.
“To date, all of the COVID-19 vaccines have been provisionally approved in Australia. I know that worries some people, but it really shouldn’t – the process is robust,” Rosalie says.
First, Rosalie and her team submit a justification to TGA as to why they should consider the vaccine for provisional approval. If their justification is accepted, the application process kicks off, which means compiling and submitting a comprehensive dossier of scientific evidence.
“The dossier includes the results of clinical trials (studies with humans) and non-clinical trials (studies with animals), as well as detailed information on chemistry, manufacturing and control, and risk management plans,” Rosalie explains.
“We put in as much information as we have at the time, to answer a range of questions: How is the product made? How is it made safely? How is it made consistently? What will its labels look like? What is the consumer medicine information going to say? What will the product information for doctors say?”
The TGA then scrutinises the dossier, working through all the information in detail and making sure every risk is covered off.
Finding and filling gaps in clinical data
According to Rosalie, the approval and registration process is iterative. Any gaps are interrogated in an ongoing way.
For example, if clinical data is lacking in a sub-population (say, those with a specific, pre-existing medical condition), the dossier must show how additional studies will fulfil this. The TGA may also request rolling submission of clinical data from trials that are in progress, but not yet completed.
“Within the context of the pandemic and the urgent need for COVID-19 vaccines, there’s a continual flow of information. The TGA is really in the loop with clinical data – they’re getting copies of the results as they’re being announced in the US and Europe. All the information from real-world use, the millions of doses rolled out all around the world, all of that safety information is being provided to regulatory agencies, pretty much in real-time,” Rosalie says.
“We’ve never seen such a level of transparency and cooperation between industry and regulators. You get a real sense that this is history-making.”
Over time, as more clinical data becomes available, Rosalie and her team will consolidate it to convert the vaccine’s provisional approval to a full approval. They’ll also work on other regulatory aspects, like getting the vaccine’s medical indication extended for specific age groups (Moderna was recently approved for 12 to 17-year-olds, for example) or doing variations for additional manufacturing and testing sites, as needed.
Compared to pre-pandemic times, Rosalie says, the scientific effort to get COVID-19 vaccines approved has become faster, better connected and more intense.
“Before the pandemic, you’d typically have a full dossier and a standard milestone-based review process. During a global pandemic, it’s not like that. It’s all accelerated. The questions are constant and for my team and I, it’s a situation of ‘respond as soon as you can, with everything you’ve got.’ And even after approval, there’s lots of ongoing monitoring and regulatory maintenance,” Rosalie says.
“I mean, you’ve got companies and regulatory authorities doing trend analyses on the data to see what it’s telling them, as they receive it. Globally there would be thousands of people working on just this aspect alone! There’s so much effort that goes into it – I’m surprised we’ve had enough scientists and statisticians in the world to work on this. It’s a great time to be a scientist!”
Commercial considerations and next steps
Rosalie and her team are also providing commercialisation services for Moderna. Generally, most commercialisation plans are modular, and the level of complexity depends on how the company intends to operate locally.
“If a company is setting up their own local entity, rather than partnering with an existing local distributor, they’ll need to consider things like pharmacovigilance, which is where you’re collecting information on adverse events and reporting those to the Australian government. It means they’ll need to have a call centre that patients and healthcare professionals can ring and ask questions like 'When is the product coming? What if I've left the product out of the fridge for two hours – can I still use it? My patient has a pre-existing medical condition – is it OK for them to have this product?'” Rosalie explains.
“They’ll also need to put procedures in place around product recalls and create localised work instructions to supplement their international standard operating procedures. Last but not least, they’ll need a number of permits, certifications and licenses to be able to bring their product into Australia, particularly if it meets the definition of a biological product, like a vaccine.”
In Moderna’s case, to execute the commercialisation plan Rosalie and her team will liaise with a wide range of Australian stakeholders – from TGA Laboratories, to the Australian COVID taskforce, Australian Border Force, and the Department of Agriculture, Water and Environment. They’ll also work with teams in the US and Europe.
To best manage the volume of work across multiple time-zones, Rosalie has grown her staff. Her latest hire? La Trobe alumna Aleksandra Zvezdakoski (Bachelor of Science (Hons) 2016), who’s joined Adjutor as a regulatory consultant following roles at GSK, Commercial Eyes and Pfizer.
For Rosalie, Aleksandra and the rest of the team, there’s no doubt working with Moderna is a career highlight.
“A project like this is what we live for. My whole team is over the moon that they’ve been able to be part of something so important,” Rosalie says.
“It’s not just about healthcare, it’s about everything from the economy to people being able to travel to see their loved ones. When you take a step back from the day-to-day detail of it, it’s satisfying to realise it’s that big.”