Out of all biopharmaceutical products, vaccines are subject to perhaps the most stringent regulatory oversight. This is unsurprising given that they are administered to enormous numbers of healthy individuals. The intense scrutiny of vaccines includes requirements for significant post-approval market surveillance.
Even before the emergence of COVID-19, it was widely accepted that vaccine development was slow. Depending on the country (or province), even clinical trial approval can take over a year. With such a focus on safety, the reality is that vaccine clinical trials will always be somewhat time consuming. However, efforts are being made to accelerate the process; some regulators, for example, offer fast-track designation, accelerated approval, priority review, or other similar frameworks for certain products. In fact, some regulators began considering the feasibility of accelerated vaccine development for a pandemic long before COVID-19. For example, the EMA put in place emergency procedures to speed up the assessment and authorization of a pandemic vaccine; it allows vaccines to be developed and authorized before a pandemic, but not marketed (this is known as conditional marketing authorization). Unfortunately, such preparedness does not apply when a pandemic pathogen is unknown. Meanwhile, the FDA has the power to grant emergency use authorization for certain products, if specific criteria are met.
Currently, however, there is no fully established regulatory pathway for pandemics caused by emerging infectious diseases. One structural gap is the lack of an explicit pathway for local regulators to leverage recommendations from larger regulatory authorities, such as the EMA and the FDA. Such a pathway could enable local regulators to benefit from additional regulatory authority expertise to reduce review and approval times of new vaccines at the country level. Right now, existing blockbuster vaccines can have more than 100 regulatory files; that’s one for each country where the vaccine is distributed.
Some novel initiatives are being seen from other stakeholders; for example, the WHO’s Solidarity Trial aims to accelerate the search for effective COVID-19 treatments. The WHO has been working with numerous parties to develop clinical trial protocols that do not rely on placebo controls. That could help by i) speeding up initiation of trials, ii) enabling comparisons between multiple sites and products, iii) streamlining data collection and processing, iv) establishing surrogate endpoints, and v) improving integration for regulatory submissions.
Other more controversial ideas have emerged to try to accelerate the process; for instance, the WHO is considering the use of human challenge studies (the controlled infection of volunteers with the SARS-CoV2 virus to verify vaccine efficacy) but these are subject to ethical consideration.
The WHO has been working with numerous parties to develop clinical trial protocols that do not rely on placebo controls. That could help by:
- Speeding up initiation of trials
- Enabling comparisons between multiple sites and products
- Streamlining data collection and processing
- Establishing surrogate endpoints
- Improving integration for regulatory submissions
It will be down to regulators to learn from the COVID-19 pandemic and establish new frameworks, but sponsors themselves also have a role to play in helping to accelerate vaccine development safely by devising new ways to speed up recruitment, facilitate how trials are run, and develop efficient manufacturing processes. From a manufacturing perspective, it is crucial that moving fast does not jeopardize safety. When clinical trials are accelerated, the whole clinical material supply chain is under pressure, and process development needs to happen in a much shorter time frame. If an insufficiently robust and poorly understood process is transferred to GMP, it can lead to deviations and scalability issues. When moving fast, developers will also not have time to build a dedicated facility, instead “adapting” an existing manufacturing facility, which can lead to more risk. Knowing your critical process parameters (CPP) and critical quality attributes (CQA) will help when it comes to discussions with regulators (which should start early!), so it is imperative that the relevant data is well captured, using data analytics software and solutions.
Companies without manufacturing experience will likely need to find an experienced partner to help them develop a feasible and efficient manufacturing process. Right now, many start-up and universities are joining the race for a COVID-19 vaccine but, although the science may be compelling, their lack of experience of clinical trials and GMP manufacturing may slow them down. We frequently see how processes with incomplete development work result in poor GMP performance. In our view, investing in a process platform can give a competitive edge because you have more data and knowledge from previous vaccine candidates developed using that same platform. We also advise companies to make use of high-throughput screening tools. For example, Ambr® can be combined with DoE software to assess design space early on. When moving into manufacturing, it is essential to use all of the data generated in the best possible way. Multivariate data analysis can be used to understand possible interactions between different CPP, which may not be obvious in a simple analysis.
Always remember that regulators not only look at clinical results, but also the robustness of the manufacturing process. Even when trying to move fast, do not neglect proper process development.
Find out more: http://ow.ly/6wpi50AFT0x
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