Although the development of a large-scale vaccine would traditionally take years to scale-up to mass production, the ambition in the face of this global pandemic is to achieve this feat in a matter of months. Every day saved in this process will saves thousands of lives, explains Dr Clive Glover, Director of Strategy, Pall Corporation.
At the same time, if a vaccine is going to be the only viable solution to stop the spread of COVID-19, we need to make sure that, as an industry, we are geared towards producing a vaccine much faster when the next pandemic hits. We need to think long-term.
A joint effort
Safely bringing a vaccine to market at this scale can’t be done by a single entity. That’s why the University of Oxford’s Jenner Institute has brought together the UK Coronavirus Vaccine Consortium, which includes leaders from various academic and industry organisations, including the University of Oxford Clinical Biomanufacturing Facility (CBF), the Vaccines Manufacturing and Innovation Centre (VMIC), Advent Srl, Cobra Biologics, Halix BV, Oxford Biomedica and my own company, Pall Corporation.
The collaboration is a joint effort; the consortium members bring different areas of expertise to the table that combine to deliver results at an unprecedented pace. The majority of consortium members are experts in GMP manufacturing — at various scales and in different locations — and are capable of combining their efforts to create millions of doses.
The original goal was to aim for one million doses by September and up to 100 million doses by the end of the year. Other manufacturers are joining in the effort all the time, such as the Serum Institute of India (SII), the world’s largest vaccine manufacturer, and AstraZeneca.
The University of Oxford announced the agreement with AstraZeneca for the further development, large-scale manufacture and potential distribution of the COVID-19 vaccine candidate in April.
As well as providing UK access as early as possible if the vaccine candidate is successful, AstraZeneca is liaising with global partners regarding the international distribution of the vaccine, particularly working to make it available and accessible for low- and medium-income countries.
Pall is part of this revolutionary consortium and global manufacturing effort because we provide pioneering technologies and services for the process development and manufacture of complex biologic drugs in the vaccine, gene therapy and mAb markets.
The challenges that we have encountered and mastered while working in these fields are very similar to the hurdles associated with scaling vaccine manufacture up to such a large scale.
For example, in gene therapies, our focus has been on how to rapidly scale-up development from small-scale academic settings to industrialised levels of production.
This is the exact challenge that we now face with the Jenner Institute’s vaccine candidate, ChAdOx1 nCoV-19 (now AZD1222) and, undeniably, with every COVID-19 vaccine currently in development … because time to market is key.
The process of developing a new drug and putting it through clinical trials, as well as constructing a production process of industrial scale, normally takes years. Thanks to cross-industry co-operation and true perseverance from those involved, we have reduced this process to a matter of a few months with ChAdOx1 nCoV-19.
Pall’s role has been to design and establish the large-scale manufacturing process, which will produce a one million dose batch of vaccine by summer 2020. To date, we have completed a process that would normally take 18 months or more. We have finalised process development and the full design phase, delivered all the equipment and manufactured and delivered all the single-use consumables.
Although time is of the essence, the most important aspect is a safe and effective process and product. This cannot be compromised. At Pall, we’ve always had a strong commitment to approaching manufacturing challenges with an integrated approach, which we believe is crucial to achieving efficacy and safety. With this consortium, numerous teams, disciplines and facilities are working harmoniously to ensure safe and robust results.
Scaling-up
Fundamentally, the scale-up process in this instance consists of developing an industrial-scale process that bears a product of equal quality to that of the CBF. This task is defined by two vital elements: the same results must be attainable using the equipment required for this much larger-scale process and characterising the performance of the equipment.
Many modern vaccines, such as those using Jenner Institute’s ChAdOx1 adenoviral vector vaccine platform, mirror many of the challenges that have driven advances in biotech manufacturing and that the gene therapy industry faces.
In the case of accelerating process development, this is perfectly aligned to support rapid development such as that needed in the fight against COVID-19. Pall’s integrated manufacturing solutions for gene therapy — and vaccines — provide scalable, well characterised processes in which individual unit operations are synchronised and co-ordinated to deliver a defined, consistent result.
It’s also worth noting that although the scale needed for the COVID-19 vaccine is large, the dose is many orders of magnitude smaller than that of many gene therapies.
Of course, some successful approaches used on a small scale aren’t appropriate when making vast quantities of a vaccine. When working with hundreds or thousands of litres of cell culture, manually pouring and transporting liquid won’t work.
That’s why we’ve designed effective procedures to move larger volumes of liquid around a manufacturing facility and certified that all technology choices are enhanced and appropriate at this scale.
Various steps in the process require adapting; whereas centrifugation is an efficient separation method on a small scale, for example, it doesn’t always work as well on a larger scale. Hence, we had to establish filtration techniques that were suitable for this specific vaccine and its scale.
We recently completed the project, and the process “blueprints,” including the instructions, equipment and consumables, have been shared with the consortium partners and licensed manufacturers to support the manufacture.
Cobra Biologics, Halix BV and Oxford Biomedica have either begun GMP manufacture or will start very soon. Our Pall team will be on hand to offer technical guidance and training to support the manufacturers and help them to run the process.
After COVID-19?
The lessons that we are learning from this process are ones that, as an industry, we can take with us. We must continue to invest in scale-up procedures as there will be more vaccines to develop in the future. COVID-19 won’t be the last pandemic that we see in our lifetimes and it might not even be the worst.
Concerns have been vocalised regarding various elements of the global pandemic preparedness, but vaccine development is one aspect that has shown remarkable speed and dexterity. This is mostly because, in the biopharmaceutical sector, we already had the means in place to quickly produce a safe vaccine … and because you can’t start producing one until you know what the virus is!
Beyond COVID-19, the platform that we’ve been working on could be used for the next pandemic outbreak and these preparations, the safety data from the clinical trials and the infrastructure put in place, will make the process faster next time. When, not if, the next pandemic hits, we will need to be able to call on the lessons this vaccine manufacture is teaching us; lives around the world will depend on it.