September 9, 2021
Vaccine development is normally a slow and laborious process. Most estimates cite an average period of around 10 years from first trials to the market, not including the decades of preliminary knowledge upon which any new research builds. The fastest development period to date was for the Mumps vaccine of the 1960s, which was developed in around four years.
By any measure, the coronavirus pandemic dramatically accelerated this process, as companies and governments raced to respond to a truly global crisis. Moderna had produced its first batch of clinical-grade vaccine by February 7th, 2020, just four weeks after the SARS-CoV-2 genome sequence was published, and within 11 months, vaccines from Pfizer/BioNTech, Moderna, and AstraZeneca had been developed, tested and given authorization for emergency use.
What was cut was not the science or the safety, but the waiting times, for both results and regulatory approval. In the process, the vaccine industry showed a remarkable adaptability and flexibility. But does this success indicate a paradigm shift in the development of other vaccines going forward? Or will it be back to business as usual?
Desperate times, desperate measures
The global pandemic created enormous political will – and public pressure – to see a new vaccine developed as quickly as possible, not present under non-crisis circumstances. This facilitated significant time savings at every step, as the typical long waits for funding, regulatory approval, and permission from ethics boards that normally hinder research were shortened from years to weeks, or even days. The US Food and Drug Administration (FDA) authorised the Pfizer vaccine just 21 days after submission, and the Moderna after 19 days, compared to an average waiting period of 10 months.
Governments and companies both accepted huge financial risks due to the high stakes of the crisis. This allowed many stages to happen in parallel that are normally consecutive, as trials began based on preliminary data, and large-scale trials began before small-scale trials had fully concluded. Usually, scaling up this fast would represent an unacceptable financial hazard to risk-averse companies, as only one in 10 vaccines trialled actually makes it to the market, but by pre-ordering huge quantities of vaccine, governments stepped in to underwrite these risks, saving months in waiting time.
By the same process, manufacturers began production alongside the trials, just in case of approval, which would not have been possible without government support. This meant that plans were in place to distribute the vaccines as soon as they were approved. Just four days passed between Pfizer being approved in the US and vaccinations beginning.
Characteristics of the virus itself also came into play. The gravity of the situation encouraged millions of citizens around the world to volunteer for trials, and thousands could be recruited simultaneously due to the rapid spread of the virus, allowing Phase III trials to be conducted much quicker than usual. Pfizer were able to recruit more than 43,000 volunteers in under 16 weeks for the final phase of their trial; in 2013, the clinical trial of another mRNA vaccine against rabies attracted just 101 participants in 813 days. Regulators helped speed up the process even more by conducting “rolling reviews” of available data, rather than waiting until each phase was concluded before beginning analysis, as is the norm. Companies usually wait to submit this data in one tranche, in case the results are disappointing.
Technology whose time had come
This unprecedented political will combined fruitfully with some promising but underutilised experimental technologies. In particular, the vaccines used two innovative new methods that had been decades in the pipeline: viral vectors (used in AstraZeneca and others), developed through research into other recent pandemics such as SARS and Ebola, and mRNA technology (Pfizer/Moderna), which had been trialled for various vaccines including Zika but never licensed, and came into its own amid the urgent need for new ideas. These so-called “platform” technologies are not developed for one virus alone, but can be relatively easily adapted to combat different viruses by substituting in their genetic information. They are then very quick to produce. Advances in genome sequencing in recent decades meant the new coronavirus could be sequenced in hours, rather than years.
A team effort
Finally, due to the global nature of the pandemic, the search for a vaccine saw remarkable collaboration between global pharmaceutical firms, biotech start-ups, health authorities, regulatory bodies, government agencies, and a range of public and private institutions in every country providing funding, research, and resources. As part of this process, new institutional infrastructure was created to share information and centralise data, and vast amounts of funding were released to public-private partnerships, such as Operation Warp Speed in the US, which committed $10 billion of federal funds to support research.
A blueprint for future vaccines?
The example of 2020 demonstrates what scientists can do without the normal obstacles. But now the question is: are there any lessons from the search for a coronavirus vaccine that can be scaled out to other vaccines? Many of the factors in play here are unlikely to be replicated more broadly for ‘peace-time’ vaccine development. Not every vaccine can be put to the front of the queue for funding and regulatory approval. Not every virus spreads so quickly, allowing data to be collected so fast, and without the threat of disruption from extended lockdowns, the public will obviously not be as motivated to volunteer for trials.
As the crisis recedes, it is also likely that, without government support, the industry will again come up against the commercial obstacles that were effectively sidelined in the search for a Covid-19 vaccine. “If people are not underwriting the risk, then manufacturers will go back to their risk-averse policies,” said Dr Stephen Morris, a research fellow in vaccine production at UCL.
However, there are some reasons to believe that lessons from this process will be put to good use. Firstly, the successful Pfizer and Moderna vaccines have provided a proof of concept for mRNA vaccines, long spoken of as a key hope for the future. Their adaptability and flexibility is raising hopes of a new dawn in vaccine development; Florian Krammer, a Professor of Vaccinology at the Icahn School of Medicine at Mount Sinai in New York claims that, using such technology in conjunction with the lessons learned from Covid-19, the process can be refined to develop vaccines in as little as three months.
Furthermore, many institutions, in search of ways to speed up their working processes, will have found new ways of working that could form the basis for systemic change, innovation, and increased productivity. Companies could redesign and simplify trials procedures, focusing on speed and efficiency and addressing previous obstacles highlighted by this experience, though whether these are sustainable in non-crisis circumstances will clearly depend on the particular specifics of each case. Some companies may also see the value in bolder investment strategies, in the case of viruses and medical conditions which are particularly lacking in available treatments.
For their part, governments can act now to build the infrastructure for future pandemics, streamlining decision-making procedures, hardwiring best practices identified during this pandemic into preparations for the next to increase readiness and robustness in the system. The example of annual flu vaccines, updated regularly according to the most current information, provide a possible model. Governments could also increase funding for research into the adaptable platform technologies that played such an important role in the development of the Covid-19 vaccines.However, in the absence of the urgency of a crisis, the most lasting positive legacy of the Covid-19 pandemic may prove to be the collaborative channels created between the many institutions, organisations, laboratories, logistics companies, government agencies, and research facilities around the world, which have shared big data in new and unprecedented ways. It stands to reason that, faced with a common problem, humanity’s best option is to work together for a common solution.
