Scientists propose new truncated process for developing COVID-19 vaccines at "pandemic speed"

Scientists have proposed a new truncated process for developing vaccines quickly during a pandemic, with a fast start and many steps executed in parallel before confirming a successful outcome of another step, an approach they claim can help stop the COVID-19 crisis.

According to the researchers from the Coalition for Epidemic Preparedness Innovation (CEPI), vaccine development is a lengthy, expensive process with high rates of attrition, typically taking multiple candidates, and many years to produce a licensed therapeutic.

CEPI, which includes Nicole Lurie, Distinguished Health Policy Fellow from the University of Pennsylvania in the US, is a foundation that finances independent research projects to develop vaccines against emerging infectious diseases.

In an article, published in the New England Journal of Medicine, experts from CEPI said vaccine developers usually follow a linear sequence of steps, with multiple pauses for data analysis or manufacturing-process checks due to the cost and high failure rates of the process.

However, with a quick start and phases executed in parallel, such as scaling up manufacturing before successful confirmation of the outcomes, the scientists believe the process can be fast-tracked, but with high financial risks.

They said for some vaccine platforms which have yielded significant success in humans, phase I clinical trials may be able to proceed in parallel with testing in animal models.

According to the researchers, an ideal platform for this new paradigm would support development from viral sequencing to clinical trials in less than 16 weeks.

Such a truncated process, they said, can demonstrate the successful and consistent activation of immune responses in humans, and be suitable for a large-scale manufacturing platform that is independent of the pathogen.

Citing an example, they said Moderna's mRNA-based SARS-CoV-2 candidate vaccine entered a phase I clinical trial on March 16, less than 10 weeks after the first genetic sequences were released.

The proposed paradigm, the scientists said, requires multiple activities to be conducted at financial risk without knowing whether the vaccine candidate will be safe and effective.

Among those with the greatest potential for quick development are DNA- and RNA-based platforms, the researchers noted in the article.

They explained that both these genetic material-based vaccines can be made quickly since they do not require culture or fermentation, but instead use synthetic processes.

According to the researchers, the use of next-generation genome sequencing may also cut development time of more conventional vaccines during epidemics.

Among other ways of hastening the process, they said testing in a suitable animal model, and rigorous safety monitoring in clinical trials will be critical.

The scientists also suggested that manufacturing steps could be scaled up to commercial levels before data on the trial's outcomes are available.

However, they cautioned that building manufacturing capacity can cost hundreds of millions of dollars.

With novel platform technologies, the article also warned that there is additional cause for concern since large-scale production of these vaccine prototypes has never been done.

For these platforms, the scientists said, facilities capable of producing large quantities must be identified, technologies transferred, and manufacturing processes adapted, all without knowing if the vaccine candidate is viable.

But since it's unclear if these new platforms will be scalable to produce sufficient quantities of vaccine fast enough, they recommended that vaccines also be developed using tried-and-true methods in parallel, even if they take longer to enter clinical trials.

One possible way, the scientists said, would be to test several vaccines simultaneously in a clinical trial design which uses a single, shared control group, so that more participants would receive an active vaccine.

However, they said this approach can be logistically and statistically complex, and may generate head-to-head comparative data which different vaccine developers may seek to avoid.

"A global financing system that supports end-to-end development, large-scale manufacturing, deployment, and ensures fair allocation, and protects private-sector partners from significant financial losses will be a critical component of future pandemic preparedness," the researchers concluded in the article.