Trial & regulatory procedures

Re-engineering the R&D machine to reach the 100-days goal

Making vaccines available for use in 100 days will require a paradigm shift in these areas of vaccine development.

In the race to make safe and effective vaccines available within 100 days of a pandemic threat being detected, having the right manufacturing, research and clinical tools in place is key. But this is just the start. The world also needs to re-design the vaccine development model so that much more work is done ahead of time, while at the other end of the spectrum crucial follow-up studies continue after emergency use has commenced.

The challenge is great. No vaccines have ever been developed faster than those for COVID-19, yet the 326 days it took to secure the first emergency use authorisation from a stringent regulatory agency was still more than three times longer than our 100-day aspiration. Bridging that gap is daunting – but doable.

Transforming vaccine R&D

There are a range of non-trivial advances that can be made across vaccine candidate development, preclinical modelling, dose-ranging, clinical safety, immunogenicity and efficacy trials. However, incremental improvements alone will not be enough. Optimising the unprecedented development timelines achieved in the COVID-19 pandemic would likely only compress timelines by around 15-25%. Getting down to 100 days requires a paradigm shift in the three stages of vaccine development: readiness, response and rollout/regulatory review.

This does not mean reducing existing standards. Rather, it is about understanding development contingencies, while at the same time leveraging new technologies and scientific insights. 

The task is analogous to the transformation in cycle times in Formula 1 pitstops. In motor racing, greatly increased levels of preparation and parallel processing means that what used to take over a minute can now be done in less than two seconds, with no compromise in driver safety. That 97% reduction in time spent in the pitstop is comparable with the reduction we are seeking from the traditional vaccine development timeline of around 10 years.

As with racing cars, redesigning the tools needed to get the job done will be critical. And this starts with a quantum leap in preparedness work prior to any outbreak.

Specifically, we need to enable rapid vaccine candidate design and selection by developing prototype vaccines for priority pathogens. Encouragingly, we now have tried-and-tested platforms for rapid vaccine development in this COVID-19 pandemic, including mRNA technology, and we can leverage artificial intelligence (AI) to help in designing immunogens, the active element that produces an immune response. 

We also need plug-and-play assay platforms – including standardised processes, reagents and raw materials – that will allow us to rapidly evaluate the comparative efficacy of different vaccines.

By combining these ingredients, researchers around the world can establish a library of prototype vaccines against the viral families known to infect humans and generate prototype safety and dosing evidence through clinical trials that are conducted before any outbreak occurs.

Doing vital research in “peacetime”

In effect, we will be pulling forward vital research into “peacetime”, rather than scrambling to do everything at once when the next crisis hits. 

To make this work seamlessly, we need to find appropriate preclinical models; build a repertoire of assays to test samples throughout the vaccine development phases; make harmonised assays globally available through a centralised laboratory network; and establish a global network of clinical trial sites, including pre-enrollment of study cohorts.

All this can be done before a future outbreak is recognised and the 100-day clock starts ticking so that during the critical phase, scientists can accurately characterise the pathogen responsible for the outbreak and shift to adapting prototype vaccines and create pathogen-specific versions. This process will involve building on prior safety data and, for example, established markers for efficacy, to develop a vaccine with performance and safety characteristics sufficient to justify emergency use within a scenario-based benefit-risk assessment.

Ultimately, the decision as to whether any vaccine can be rolled out in a particular situation will be a judgment call for regulators, based on a benefit-risk assessment that considers both the lethality of the pathogen and the strength of the vaccine data. But by having a solid package of evidence on prototype vaccines ready ahead of time, it should be possible to break the “firewall” between clinical trials and public health interventions so that confirmatory data continues to be collected after initial deployment.

The fact is that large Phase 3 vaccine efficacy trials involving two doses of vaccine, usually given at least four weeks apart, cannot be started and completed within 100 days, so pushing the majority of enabling steps to before and after is unavoidable.

In future global health emergencies, the rapid rollout of vaccines based on pre-established safety data should go hand-in-hand with the ongoing assembly and review of real-world evidence of efficacy. This represents a change in the traditional mindset and will require an adaptation in regulatory protocols. But it is less radical than it might seem at first glance. Such an overlap already occurred to a degree with COVID-19 vaccines, and the concept of regulatory approval based on data from closely related products is well established for seasonal flu shots, where routine annual changes are made without new clinical trials.

Faster vaccine development will save lives in future, dangerous, outbreak situations and the right investment decisions made today will be crucial in reducing the risks posed by tomorrow’s disease outbreaks. If we get it right, we may be able to stop future epidemics from becoming pandemics altogether. 

Find out more about the 100 days mission here.