Onshore manufacturing has an obvious advantage during a pandemic, as importing products from international manufacturers can face competition from other countries. This was seen during the COVID-19 pandemic, with Australia falling far behind other developed countries in vaccination campaigns and struggling to receive vaccines from abroad.
By 2030, Australia wants to be in a position where it has onshore vaccine manufacturing capabilities and infrastructure for clinical trials across a diverse range of vaccine technologies: with the infrastructure designed to be ready to pivot swiftly towards large-scale pandemic manufacturing if required.
Australia does possess inactivated virus and live attenuated virus manufacturing capacity through Melbourne-headquartered CSL.
Onshore manufacturing is currently heavily complemented by partnerships with international vaccine manufacturers to secure supply of vaccines, including Pfizer and Moderna. Australia also has a range of research institutes and contract development and manufacturing organizations (CDMOs) that further develop candidates for manufacture at a scale to support clinical trials.
But scaling up to pandemic-scale infrastructure comes with its challenges: the long lead times in developing infrastructure, skills and processes; ongoing investment to maintain supply chains and keep facilities ‘warm’; and an appropriately trained workforce.
Recent investments have been starting to boost onshore manufacturing capacity: such as Moderna's decision to build a mRNA facility in the country and Seqiris / CSL's investment in a cell-based influenza manufacturing facility.
A new report from CSIRO, Australia's National Science Agency, sets out two key recommendations: to diversify onshore manufacturing capabilities across vaccine types; and secondly to boost clinical trial scale manufacturing to create a pandemic-ready infrastructure.
Diversifying vaccine types
The report, 'Strengthening Australia's Pandemic Preparedness', recommends diversifying manufacturing capabilities across vaccine types, including recombinant protein and viral vector technologies.
“Australia’s population scale manufacturing capabilities are limited to live attenuated and inactivated virus vaccines technologies," notes the report.
"These technologies are likely to continue to play a role in global vaccine products and be supported by planned mRNA manufacturing capacity.
“However, other vaccine technologies may be the most effective at responding to Disease X."
Diversifying onshore manufacturing to include additional vaccine technologies, therefore, could help prepare for the next pandemic.
"Based on Australia’s established population scale manufacturing capabilities, planned mRNA manufacturing capabilities, and technologies that are not currently commercial (i.e., DNA and self-amplifying RNA), recombinant proteins and viral vector technologies should be prioritized for future investments.
“Manufacture of recombinant proteins and viral vector technologies have varied inputs, scale of production and required infrastructure. Recombinant proteins are often complex products as they require mass purification of intermediatory products and often require an adjuvant (a substance that enhances the immune response) to be developed. Conversely, there are more than 10 different vectors that can be used in viral vector technologies and therefore infrastructure requirements vary.
"While it is unlikely Australia will be able to produce multiple additional vaccine technologies at population scale without significant government investment, Australia could export vaccine components across a variety of vaccine technologies if the nation diversifies its small-scale manufacturing capabilities.
"For example, there is potential between pandemics for Australia to value-add by exporting drug substances for fill and finish to be conducted offshore for international markets. Leveraging offshore markets can support scale-up between pandemics; however, this will carry a risk for securing supply in a pandemic.”
Build up CDMO capacity
The second key recommendation is to expand the number of contract development and manufacturing facilities to support Phase I to III trials for vaccines.
At the moment, fewer and fewer late stage clinical trials remain in Australia and intellectual property value is lost offshore due to high input costs and a comparatively small population to support trial patient enrolments.
Australia also faces barriers to onshore manufacturing at population scale due to high input costs and limited export opportunities, as the surrounding region is well serviced by existing manufacturers.
“Increasing the number and breadth of CDMO facilities, including in technologies where Australia does not have established population scale manufacturing, can attract and offer flexibility to companies looking to bring emerging vaccine technologies to market," notes the report.
“Access to versatile CDMO infrastructure can reduce the timelines and cost to vaccine developers, as it reduces financial risk until the vaccine is shown to be effective in late-stage clinical trials.
“Existing Australian CDMOs have competing commercial pressures in a pandemic and are unlikely to be suitably reliable for national needs. Further, it is not feasible for government to provide ongoing financial support for new CDMO facilities across all available vaccine technologies, particularly between pandemics.
"Public‑private partnerships provide an alternative to the status quo in Australia. A public-private model would assist with securing the supply of vaccines in a pandemic as multiple facilities would have existing partnerships with government.
“Such CDMO facilities could service Phase I to III clinical trials and small end commercial manufacture (e.g., cancer vaccines or vaccines for small scale infectious disease outbreaks) with batch sizes in the low millions."
One such example of this is a 2013 capital investment from the Federal and Queensland Governments to set up a new mammalian cell culture facility. This investment attracted international manufacturer Patheon, a subsidiary of Thermo Fisher Scientific, to develop a CDMO business at this facility in Brisbane. The site specializes in good manufacturing practice (GMP) for clinical (Phase I to III) and small-scale commercial manufacturing and is co-located with the Translational Research Institute. The facility collaborates with domestic universities on development of mammalian cell lines and has grown local advanced manufacturing jobs.
Ready to scale up
Such facilities should target commercial opportunities, particularly in between pandemics, to keep infrastructure ‘warm’ and pivot capacity to respond to a pandemic.
"The scale of production (i.e., the size of the bioreactor) for clinical trials varies across vaccine technologies. For example, a 50-litre bioreactor can produce millions of doses of a mRNA vaccine, but a recombinant protein would need a much larger production scale. Greater analysis is required to determine the ideal scale of these CDMO facilities and which vaccines technologies initial facilities should focus on.
“As the number and scale of manufacture of CDMO facilities increases, opportunities to attract international companies will also increase. This will be enabled by proven process validation at a facility and gaining international regulators’ approval for safety by meeting stringent current good manufacturing practice (cGMP) requirements. Engagement with international companies can improve knowledge and expertise in delivering commercially ready manufacturing services.”