Dr Clive Glover, director, strategy at Pall Corporation, discusses the steps the pharmaceutical industry has taken to speed up the development of a Covid-19 vaccine.
Vaccine research
The world has been under lockdown for several months now. Although some locations have loosened restrictions, a safe and effective vaccination will be a crucial element in many countries’ “exit strategy” for Covid-19. The reimplementation of lockdown in Northeast China amid new clusters of infection is a grim reminder of that reality.
While development of a large-scale vaccine would traditionally take years to scale-up to mass production, the unprecedented scope of the pandemic has accelerated the timeline to months, not years. Every day saved in this process corresponds directly to lives saved.
Some of the world’s greatest scientific minds are currently working night and day in this race against the clock, to find a solution. Although this isn’t the first pandemic we’ve faced - we’ve had SARS, MERS, swine flu, bird flu - Covid-19 is one of the worst the world has experienced in modern times.
Tackling this current pandemic is priority one, but we need to think long-term about our ability to respond when a similar threat emerges in future. If a vaccine is going to be the only viable solution to stop the spread of Covid-19 ,we need to make sure as an industry we are geared towards producing a vaccine much faster when the next pandemic hits.
A Collaborative Approach
Bringing a vaccine to market quickly and safely, particularly at the scale needed now, cannot be done by a single organisation—the magnitude is simply too massive. The University of Oxford’s Jenner Institute has recognised this and brought together the UK Coronavirus vaccine consortium team, which includes leaders from numerous 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, AstraZeneca, and my own company, Pall Corporation.
We are involved in this groundbreaking consortium because Pall provides innovative technologies and services for process development and manufacturing of complex biologic drugs in the vaccine, gene therapy, and mAb markets. Similar challenges are seen across these various areas and the lessons learned from our broad experience help us continually improve processes and adapt to change or patient demand. In gene therapies, for example, we’ve been focused on how to quickly scale up development from small-scale academic settings to industrialised levels of production—which is the challenge we now face with the Jenner Institute’s vaccine candidate, ChAdOx1 nCoV-19, and indeed with every Covid-19 vaccine currently in development as time to market is critical.
ChAdOx1 nCoV-19 uses a well-studied chimpanzee adenovirus vector combined with the genetic material of SARS-CoV-2 spike protein. The technique is known to generate a strong immune response and has an excellent safety record, which should enable its use in children, those with preexisting conditions, and older individuals. Though others are being researched, the ChAdOx1 based vaccine is widely seen as the front-runner in the race against the virus.
To develop a new drug, put it through clinical trials and then build out a truly industrial production process would normally take several years. With ChAdOx1 nCoV-19, we have condensed this process to a period of a few months, thanks to an unprecedented cross-industry collaboration and countless man hours from the many individuals in the consortium. Pall’s role has been to design and establish the large scale manufacturing process, which will produce a 1-million doses/batch of vaccine by summer 2020. In just eight weeks, we completed process development and the full design phase, delivered all equipment and manufactured and delivered all single-use consumables. This process would normally take 18 months or more.
AstraZeneca has now begun manufacturing the vaccine ahead of the clinical trial results, and has doubled its capacity to two billion doses. It has also signed partnership agreements with the Serum Institute of India (SII), the world’s largest vaccine manufacturer, and with two health organisations backed by Bill and Melinda Gates, that will see half of the doses supplied to low and middle-income countries.
This spirit of collaboration and innovation is what has been driving the consortium from the start and is showing what can be achieved when organisations and experts from all over the world come together to solve a truly global problem.
Scaling up
The scale-up process has involved creating an industrial-scale process that produces equivalent quality product to that produced at the CBF. This challenging task comprises three main elements: proving that the same results can be achieved using equipment needed for this much larger process, characterising the performance of the equipment, and making sure that the output is equivalent to that of the small-scale process.
Manufacturing modern vaccines such as ChAdOx1 n-CoV-19 (now AZD1222) brings with it many of the challenges that have driven advances in biotech and the gene therapy industry alike. Having long been leaders in these fields, our intimate knowledge of these considerations has enabled us to pivot to large-scale vaccine manufacture quite naturally. And remarkably, though the scale needed for the Covid-19 vaccine is large, the dose is many orders of magnitude smaller than that of many gene therapies.
That said, clearly some strategies that work on a small scale aren’t suitable to make vast quantities of vaccine. Pouring and transporting liquid manually cannot apply when you’re working with hundreds or thousands of liters of cell culture. So we’ve designed efficient processes for moving larger volumes of liquid around a manufacturing facility and ensured all technology choices are optimised for suitability at this scale For example, centrifugation is an effective separation method at a small scale but doesn’t always work as effectively at a larger scale—so the challenge was to develop the filtration techniques appropriate for this particular vaccine and scale.
When our part of the project is complete in the coming weeks, we’ll hand the “blueprint”—sets of instructions, equipment, and consumables—to Cobra Biologics, Halix BV, and Oxford Biomedica to begin GMP manufacture. The finished process will enable batches of one million doses per manufacturing run, with even more possible later in the year. Pall will continue providing technical support and training to ensure that the manufacturers are able to run the process successfully.
Looking forward
The concept that is of singular importance to every member of the consortium is that the process and product are effective and safe every time. Though time is of the essence, neither of these critical elements can be compromised. Pall has always had a strong commitment to approaching manufacturing challenges with an integrated approach, which we believe is crucial to achieving efficacy and safety. In the ChAdOx1 nCoV-19 consortium, multiple disciplines and facilities are working in concert to arrive at robust and safe results. The fact that the clinical testing portion is running in parallel with our manufacturing process work also hastens the process and improves the outcome.
The reality is that Covid-19 will not be the last pandemic we see in our lifetimes. It may not even be the worst. Many have raised concern over various elements of the global pandemic preparedness. However, vaccine development is one area that’s shown impressive speed and agility, largely because industry already had tools in place to produce a safe vaccine quickly (and you can’t start producing until you know what the virus is).
There are lessons the industry can take with us. We need to continue to innovate and invest in how we scale-up manufacturing, as there will be more vaccines to develop in the future. There will also be breakthroughs in biological drug development for acute and chronic illness, which will need rapid scale-up. The platform we’ve been working on will likely be applicable in the next pandemic, and these preparations, infrastructure, and the safety data from the clinical trials will make the process even faster next time. When, not if, the next pandemic hits, we need to call on the lessons we are learning today. Millions of lives will depend on it.