What does it take to get regulatory approval of vaccines?



Published 26 October 2020
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The world is holding its breath for a vaccine to save lives, as over 100 vaccine candidates to fight the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development. As of today 48 vaccines are in the human trials. Global authorities, scientists and business and health organisations are racing not only to find a vaccine, but also to be the first to obtain approval for a COVID-19 vaccine. However, as history has shown, safe vaccines usually take years to develop.

By Knut Sverre Skurdal Andresen & Anuschka Teresa Hager-Thoresen

For the sake of safety and efficacy, developing vaccines takes time and only a few candidates end up meeting the requirements to obtain approval. In average, it takes 10-15 years until a vaccine is fully approved. Some vaccines have even taken over 25 years to develop. The mumps vaccine from the 1960's is currently holding the record of obtaining market approval within only four years. Dr Hillemann, then head of the virus research department at Merck & Co., which is now one of the largest multinational pharmaceutical companies in the world, took a swab of his daughter's throat who had been complaining of a sore throat. The strain of mumps virus (called Jeryl Lynn after Dr Hillemann's daughter) is still used in vaccines given to newborns all over the world.

It all starts in the lab. Before starting with trials, scientists need to understand how the virus proteins are structured, its genetic sequence and how it responses to human or animal cells. With this knowledge, scientists try to find the right antigen – the substance your immune system does not recognize and thus will produce antibodies to fight off.

This antigen – the vaccine candidate – is tested in the lab and on animals under controlled conditions to check whether the animal produces an immune response. Many candidates will already fail at this stage, either for being harmful or simply not working. Once the safety and potential of the candidate has been established, the candidate moves into clinical trials, which are conducted in three phases. Clinical trials have to follow strict standards and protocols and are overseen and inspected by governmental authorities such as the European Medicines Agency (EMA) in Europe, the US Food and Drug Administration (FDA) in the United States and the Ministry of Health, Labor and Welfare (MHLW) in Japan. In each phase of the clinical trials, the number of healthy volunteers is increased. For each phase, there are different and more detailed aspects of the candidate to be verified:

Phase I

  • Does the vaccine seem to work?
  • Are there serious side effects?
  • Is the vaccine safe?

Phase II

  • What are the most common short-term side effects?
  • What is the optimal dose?
  • How are the immune systems of the participants responding to the vaccine?

Phase III

  • Is the vaccine effective, i.a. how many people are getting infected after having received the candidate?
  • What are the most common side effects?
  • Is the vaccine safe?

Results from the studies are then submitted to the authorities for scientific evaluation to determine whether the benefits of the vaccine are fare greater than the risks. If approved, the vaccine obtains marketing authorisation (MA). Currently there are no candidates for COVID-19 approved for full use. However, four Chinese COVID-19 candidates and two Russian COVID-19 candidates are approved for early or limited use, without having received the results of the Phase III clinical trial results yet. Russia has announced it will release temporary data from Phase III clinical trial in November.

In order to accelerate the development of a COVID-19 vaccine, extraordinary measures have been implemented throughout the world. Under the Federal Food, Drug and Cosmetic Act, the FDA may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat or prevent serious or life-threatening diseases or conditions caused by chemical, biological, radioactive or nuclear (CBRN) threat agents when there are no adequate, approved and available alternatives.

In the European Union, the EMA has adopted a separate and expeditious grant procedure for incoming applications for approval of vaccines and other pharmaceuticals applicable for the treatment and prevention against COVID-19. A MA recommended by EMA and approved by the EU Commission will be valid for all EEA countries, Norway included.

Still, after having received a MA, pharmaceutical companies will need to facilitate for manufacturing infrastructure tailored to the specific vaccine production. Once the manufacturing infrastructure is in place, producing vaccines on a large scale will take some time as well. Following the manufacturing, the vaccine will need to be distributed, which due to social distance requirements have to be done in stages and controlled forms.

Even if the history of vaccines and the procedures of vaccine development itself have shown that the successful development of a safe vaccine takes time, the outbreak of COVID-19 has so far been proof that not only a virus but also the human ability to solve and overcome regulatory, scientific and practical issues can move with pandemic speed.