How COVID-19 vaccines can win approval from medical regulators

Simone McCarthy, South China Morning Post

Posted at Oct 31 2020 08:18 PM

This handout picture taken on August 6, 2020 and provided by the Russian Direct Investment Fund shows the potential vaccine against the coronavirus disease, developed by the Gamaleya Research Institute of Epidemiology and Microbiology. Russian Direct Investment Fund, Handout/AFP

The race to stop the spread of Covid-19 has triggered the fastest development of vaccines in history as pharmaceutical companies condense a process that typically takes years into a matter of months.

A number of candidate vaccines are expected to report results from their final phase trials in the coming weeks and months, and the process is shaping up to be a challenging time for the world’s regulators with multiple vaccines that use different technologies potentially seeking approval.

The urgency of the situation – a public health emergency that has cost more than 1 million lives worldwide – means that regulators will seek to balance risk with benefit.

What does it take to get a vaccine approved?

Vaccines are vetted through the multiple stages of a clinical trial.

The first two phases show if an experimental vaccine is safe and produces an immune response to the coronavirus in the lab.

Successful candidate vaccines then progress to large-scale phase 3 trials, which evaluate whether they will protect people against Covid-19 and conduct further safety checks.

Phase 3 trials are designed with certain parameters to judge whether the vaccine is working.

This information is typically kept under wraps, but several major pharmaceutical companies from Europe and the US have taken the unprecedented step of releasing the full protocols they will use.

These tell observers at what points these vaccine makers may ask regulators to evaluate their data.

For example, Pfizer will conduct its first interim assessment when 32 of their 42,000 test subjects become infected.

If no more than six of those cases are people who have received their vaccine – showing it is around 77 per cent effective – and they fulfil safety and manufacturing quality criteria, then the company has said it will seek an emergency use authorisation from US regulators.

What’s the difference between emergency use licensing and approval?

While different countries have different rules, there are mechanisms that allow regulators to grant permission for the use of an unapproved product during a public health emergency.

The World Health Organization also has a process for “emergency use listing” for vaccines.

Several vaccines are already in use under such mechanisms.

In China, where three vaccines have been granted emergency use authorisation, hundreds of thousands of people have already been vaccinated. These include vaccines made by Sinopharm, which have also been given emergency use authorisation for high-risk groups in the United Arab Emirates, where the clinical trials are taking place.

But there are concerns about such authorisations, including the risk of administering vaccines before the trials finish, and the WHO’s chief scientist said they should be seen as only a “temporary solution”.

Scientists have also said that taking this route could result in the loss of valuable data, if it interferes with the completion of trials.

What are regulators looking for in approving the vaccines?

In general, regulators are looking for three things: safety, quality and efficacy. They will run their own statistical analyses to evaluate whether vaccine candidates are up to standard. Manufacturing quality and consistency are also evaluated.

Some regulators have already laid out specifications for what they will need to see from vaccine makers’ data.

In the United States and China, for example, vaccine makers will need to prove that their Covid-19 vaccines have an efficacy rate of at least 50 per cent – meaning that those who have been vaccinated are half as likely to get infected as members of the placebo group. This is also the benchmark laid out by the WHO.

Regulators and international bodies such as the International Coalition of Medicines Regulatory Authorities (ICMRA) have called on vaccine makers to include a diverse group of adult participants in their trials to ensure they have information about different age groups, ethnicities and risk categories.

Who are the regulators?

Most countries have their own regulatory authority, whose members 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.

An approval by respected regulators like the US Food and Drug Administration or the European Medicines Agency can guide other countries as they make their own decisions.

The WHO also has a pre-qualification process, which certifies products are safe for purchase by UN agencies and can play a similar role.

In recent months, international bodies like the ICMRA have held meetings with regulators from around the world to discuss details of Covid-19 vaccine development.

What happens after vaccines go to market?

The regulatory process does not end with the licensing of a vaccine. Additional studies will be needed for some groups like children, as trials so far have focused on adults.

Phase 3 trials themselves often monitor participants for a period of years after they received the vaccine to continue to collect data.

“Post-marketing surveillance” is considered an important way to monitor safety after vaccines are released. This is likely to be done both by countries and the pharmaceutical companies. These processes are meant to ensure that any adverse effects that emerge when the vaccines are used on a mass scale will be identified and addressed quickly.