Explainer | If a coronavirus vaccine passes human trials, how does it get approved?
- There are dozens of vaccines in development but there is still a regulatory process to go through
- With regulators under enormous political pressure to approve a vaccine, public trust will be critical to success
In the background, though, teams of scientists were deconstructing the virus that causes Covid-19 and how the body fights it, in the hope of developing a vaccine, an ever more urgent task as the pandemic claimed more than 700,000 lives.
There are more than two dozen vaccines now in human trials, as developers seek to speed up a process that typically can take years.
Money is no object as governments pledge billions of dollars for vaccines to not just save lives, but also rescue the world economy and millions of livelihoods.
What does it take to get a vaccine approved?
The first clinical trials show if an experimental vaccine is safe and produces an immune response to a virus. Successful candidate vaccines progress to Phase 3 trials which evaluate whether they will work to protect against Covid-19 in thousands of test subjects.
What happens next will be in the hands of regulators in multiple countries.
While it is not certain any candidates will prove effective enough to seek approval, experts say the anticipated regulatory process is shaping up to be challenging.
Multiple vaccines using different technologies may undergo licensing and all countries are likely to be looking to bring products to their market at the same time.
Meanwhile, there is enormous political pressure to approve vaccines quickly, prompting health regulatory officials around the world to say regulatory rigour will not be influenced as they decide which vaccines, if any, end up being jabbed into the arms of hundreds of millions of citizens.
Who are the regulators?
Most countries have their own regulatory authority that will need to approve any vaccine before it can be distributed, even for conditional or emergency use. Regulators are typically doctors, microbiologists, chemists and biostatisticians. Usually an advisory committee made up of medical and scientific experts outside the agency will help them make decisions.
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In recent months, international bodies like the International Coalition of Medicines Regulatory Authorities (ICMRA) have held meetings with regulators from around the world to discuss details of Covid-19 vaccine development.
John Lim, executive director at the Centre of Regulatory Excellence of Duke-NUS Medical School in Singapore, said such practices could help countries make better decisions.
“That levels the playing field so that when a vaccine is available to a country with a less-resourced regulator [they can] be able to make a more informed decision,” he said.
What do regulators look for?
According to Lim: “Safety, quality and efficacy [are] the three mantras of all regulators.”
Clinical trials ideally collect as much data as possible for regulators to make a thorough assessment of risks versus benefits for any candidate vaccine.
Last month, the ICMRA issued a brief outlining the kind of information that Phase 3 trials should collect, such as how the vaccine works in diverse populations, to better understand any safety concerns.
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Regulators go through the data submitted by developers line by line as they look to evaluate any adverse effects, demographic distinctions and efficacy, according to John Donnelly, principal at US-based Vaccinology Consulting.
“They will have their own statisticians analyse the raw data and compare it with what the company has presented them with,” he said.
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But the key question – does it work – is a relative one.
How effective a vaccine needs to be to get licensed or receive an emergency authorisation is at the discretion of a country’s regulators. For example, the United States Food and Drug Administration said it might approve safe vaccines that are at least 50 per cent effective.
This means developers need to show people who are vaccinated are half as likely to get infected compared to those in the placebo group.
Will the vaccines be safe?
Public trust in vaccines is critical to the wide adoption needed for immunisations to be successful in reducing community transmission, experts say. The speed of Covid-19 vaccine development has raised concerns, but health officials around the world have said they will not compromise on safety standards.
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China’s Centre for Disease Control and Prevention director Gao Fu said last month he had received an injection from a Chinese vaccine candidate to boost confidence in its safety.
Russia on Tuesday said it had approved a coronavirus vaccine for public use, but the news raised concerns about safety given it has not been through large scale, phase three trials.
As far as international regulatory standards go, vaccine approval is based on a “risk/benefit assessment”. Regulators look at any risks that turn up in clinical trials and weigh those against the risks from the disease and the efficacy of the vaccine.
“There is always a certain amount of risk,” Donnelly said.
Some may not be picked up during a study period, when sample sizes are in the thousands, or if there is an abbreviated trial, where developers apply for an expedited approval once they have enough efficacy data, as opposed to waiting for all patients enrolled to complete their study period, he said.
“[But] with any vaccine efficacy trial, it can only go on for so long and you can only collect so much data … there are always unknowns,” he said.
These might be questions about how long a vaccine’s protection lasts or whether there will be adverse effects in one in 100,000 or 1,000,000 people, he said.
A shortened time frame put the importance on continued study after approval, which may be a condition of approval, he said.
How long until vaccines are approved?
Some health officials have said approved vaccines could reach the market early next year, although production capacity would initially be limited.
But that does not mean the regulatory process is over, experts say. Approvals could take longer for different demographic groups like the elderly, for whom additional trials may be needed.
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And risks will continue to be monitored after the vaccine is released. This is likely to be done both by countries and the pharmaceutical companies.
“When you go to a much larger population with different age groups, different demographics and disease conditions, you may still find unexpected adverse side effects,” Lim said.
“The pre-market authorisation is critical, but it has to be balanced with continual monitoring. These systems have to be in place, sometimes for years.”
