Ask and You Shall Receive: A GMP Pandemic Response, 3 Priorities from the Covid-19 Vaccine Development Process
In this blog post, Anna Osborne identifies the top three priorities for the successful scale up of the AstraZeneca Covid-19 vaccine development, led by the University of Oxford and Oxford Biomedica, and considers how lessons learned could be applied to the GMP scale-up of advanced therapies.
This follows the webinar discussion exploring the contributing factors to the successful development and commercialisation of an effective Covid-19 vaccine, on the huge scale and at the rapid response demanded by a global pandemic.
James Miskin, Chief Technical Officer at Oxford Biomedica and Sandy Douglas, Research Group Leader at the University of Oxford, had an interesting discussion surrounding their institutions own collaboration as well as that with many other companies. With hindsight on their side, our panel identified the main contributing factors that made their scale up production of an effective covid-19 vaccine possible. The discussion was moderated and included further insight from Jessica Carmen, Executive Vice President at Adjuvant Partners.
The panel examined the main challenges faced in the initial stages of the vaccine production, how these were overcome and the applications of these ideas to the future of advanced therapy commercialisation journeys.
Priority 1: Rapid Response and Collaboration
“Things moved very fast, better than we could have reasonably dreamed to hope.” – Sandy
The University of Oxford’s response to the threat of coronavirus was very rapid. As early as February 2020 they kicked off the process for developing a vaccine against this new and alarming strain.
Internal collaboration within the institute was required to utilise the expertise of specialists in all areas of vaccine production. The capacity of the institute – alongside confidence in the use of a pre-developed vector technology for this novel coronavirus – allowed for the project to start accelerating rapidly, and the team was able to begin scaling up production of the adenovirus aggressively.
The team at the University of Oxford realised that in order for the project to be viable, they had to reach out and ask for help. The first point of call was making contact with the UK Vaccine Manufacturing and Innovation Centre and putting out a cry for help across the UK bioprocesses network. A range of biotechs responded and collaborative work began.
In March 2020 Oxford Biomedica, with over 20 years’ experience of viral vector manufacturing, came on-board.
What was unique about this process, James comments, was so many organisations working collectively, who wouldn’t have previously, towards a shared goal.
At this point they transferred tech to five sites in four different countries. This enabled them to scale up batch production and provide GMP evidence that the process could be ran at scale, within the first three months.
AstraZeneca joined to oversee the project in April 2020 accelerating the pace of development further. They received much needed Investment form the UK government, as well as input from larger partners. As the project became more prominent on a global scale it gained huge manufacturing capabilities, with manufacturing taking place across 12 different countries, in order to reach the 200 billion doses of vaccine achieved today.
The success of these complex collaborations on a global scale provides lessons to the advanced therapeutics industry. Visualising the results of such a large collaboration enables other companies to replicate this, be it on not such a grand scale, for the benefit of their pipeline.
Priority 2: Business Risks Are Necessary, Patient Risks Are Not
The fast pace of the scale up meant that finical risks had to be taken.
Up until AstraZeneca came on-board, the University of Oxford had been working at a substantial financial risk to themselves, with only a small £400k grant from UK Research and Innovation. The companies coming on-board in these early stages therefore took on some of the financial burden the project was facing, allowing for it to progress.
In April 2020, the UK government provided the project a £64 million investment before even the first clinical trial for the vaccine had begun. This was a significant financial risk, but a necessary risk as the world looked towards scientists to help the state of global emergency.
The development and commercialisation processes used in this project were remarkably different to the protocols used by companies during standard vaccine manufacturing. Sandy observes how those involved showed genuine collaboration with aligned interests in this unprecedented territory. This involved honest initial conversations before the proposal of legal contracts in order to understand what they could make possible.
“We had to be scientific and clear about which risks were patient safety risks, which we weren’t going to take and which were business risks.” – Sandy
The urgency of this project is rarely seen in programmes outside of the pandemic, where products can take years to get to market. The speed and scale at which this vaccine was required meant using methods that were not usual practice and came with heavy financial and business risks, but that could save crucial days or weeks.
Patient safety was never comprised, both Sandy and James are clear about that. However, the organisations involved worked collectively making decisions that would speed up development and sharing the consequential financial risks involved.
Whilst the level of financial risk experienced in this project is very unusual in the world of therapeutic development, Sandy believes that there is a place for some of the business risks taken to be used elsewhere. The positive outcome from taking calculated business risks in this incidence makes a strong case for their use. It could also encourage others to take similar steps to advance other therapeutics, such as cell or gene therapies. James notes that this is a tricky subject to navigate, especially for a public company, and involves commitment by all parties to share the risks involved.
Priority 3: Strong Regulatory Relationships
In order for the rapid scale up of this Covid vaccine, a strong dialogue had to be maintained between the organisations and their regulators. For both Sandy and James, they capitalised on a crucial relationship with the MHRA.
“Their approach is absolutely focused on safety but they were actively engaged in what they could do to support rapid build-up of manufacturing capability.” – James
The Covid vaccine programme become a priority for the MHRA, with teams working in response to the schedules of the various organisations involved. Close coordination meant the MHRA enabled the extremely sped up approval of Oxford Biomedica’s Oxbox facility and its newly adapted complex vaccine suites, allowing manufacturing protocols to start immediately. Looking forward, the accelerated approval of the Oxbox facility provides the capacity for the sped-up development of other important advanced therapies.
The MHRA also allowed for clinical trial applications to be turned around within 24 hours, there to be a standard rolling submission on everything, and for necessary discussions and science-led advice to be provided to the organisations involved. All these factors placed values on both patient benefit as well as industrial innovation and were vital to facilitating the rapid development of the programme. The MHRA exhibited understanding and support of the projects’ diversion from standard practice to meet the demands of this unprecedented level of GMP scale up, without sacrificing their accountability of patient and process safety, installing confidence in the vaccine.
A strong regulatory relationship from the beginning of the programme, Sandy believes, was essential for the successful and rapid GMP scale up, with regulatory capacity a key boundary to vaccine access.
“Investing and having good people in that [regulatory] environment is probably one of the smartest investments for UK public health and the economy they could possibly make.’’ – Sandy
It appears evident that maintaining good regulatory relationships could pave the way for productive regulatory conversations regarding other therapeutic areas.
It is clear that there were many contributing factors in the feasibility and success of such a large scale vaccine development programme. What appears key was the shared goal and co-operation maintained between not only the University of Oxford, Oxford Biomedica and all other companies directly involved in the GMP manufacturing scale up processes, but also with the other organisations, including investors and regulators.
The collaborative recognition of the urgency and novelty of the Covid vaccine project by all parties involved, be it via taking financial risks or prioritising the projects needs and activities, enabled the production and supply of over 2 million AstraZeneca Covid-19 vaccines across the globe.
Hypothetically, if a new vaccine was required right now for a new strain of coronavirus both Sandy and James are in confident agreement that with the knowledge they now hold in the collaborative scale up process, results could be achieved even quicker.
Perhaps these unconventional methods of taking business risks and using strong company collaboration could be applied to other conditions and areas of advanced therapeutics. Accelerating and scaling up the development of many product lines could be of great benefit in advancing the industry and getting patients the treatment they need.
Want to find out more? You can watch the full panel discussion on demand, here.