How does a vaccine get approved in Europe? The process, explained
Developing a vaccine is a long road. Of the hundreds of vaccine candidates, very few meet the requirements to get approved by international authorities.
In the European Union, vaccines and other drugs, are controlled by the European Medicines Agency (EMA) and other regulators.
It usually takes an average of 10 to 15 years to develop a vaccine. But international leaders claim that one against COVID-19 could be ready in a year or two. So far, no coronavirus vaccine has ever been developed. So, is this realistic?
Here are the steps that any potential vaccine must go through to get approved for human use.
Step 1: Exploratory work
To beat a virus, researchers need to know how it works. It starts in the laboratory where scientists try to understand how the virus affects human or animal cells and determine its genetic sequence.
They will identify the structure of the virus proteins to see if they can use them to create an immune response. An effective vaccine needs to mimic an infection without making you sick.
In the case of SARS-CoV-2, this was facilitated by all the research already conducted during the SARS and MERS global outbreaks. China also shared the genetic sequence of the new coronavirus in January. This helped develop test kits and possible treatments.
The final objective of this step is to determine possible antigens - foreign objects or toxins that trigger your immune system to make antibodies - that could help to prevent or treat the disease. At the end of this stage, researchers have a vaccine candidate to move forward.
Step 2: Pre-clinical development
Before testing a vaccine on humans, scientists must perform rigorous tests to ensure that it is safe and able to produce an immune response. That’s why, at this stage, the vaccine candidate is tested in labs and animals. Many potential vaccines fail, either because they don’t work or because they are harmful.
Once these tests are completed, batches of vaccines that meet the minimum requirements for initiating human clinical trials will start to be prepared.
Step 3: Clinical trials
This is the first time the new vaccine is tested on humans.
Clinical trials have three phases.
Phase 1 trials
The vaccine is tested on 20 - 100 healthy adult volunteers, preferably young people.
Researchers need to answer these questions:
• Does the vaccine seem to produce the needed immune response?
• What is the right dose?
• Does it cause any harm?
• Are there serious side effects?
“What is important is to try to understand: 'what is the safety of the vaccine?' in this small number of subjects," explains Dr Marco Cavaleri, Head of Biological Health Threats and Vaccines Strategy at the EMA. "And the immunogenicity: 'what is the right dose?'. Or at least to have some initial ideas of what the right dose could be, to be carried on in later clinical trials”.
Phase 2 trials
The vaccine is tested on several hundred volunteers. To make the studies more comprehensive, scientists try to analyse a range of variables. The participants might come from different geographical areas, be of different ages, or any other aspect that could have an impact on the development of the virus.
Researchers are looking for:
• 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 3 trials
At this stage, the vaccine is tested on thousands of volunteers. These are the larger clinical studies.
While this is happening, the manufacturing process scales up, so initial small batches of an investigational vaccine become large batches that can be commercialised.
At the end of this process, the results will be submitted to the regulatory authorities and they will be key to whether or not a vaccine gets approved.
The EMA can only approve the vaccine if its benefits are greater than its risks.
“If everything is fine, the quality, safety, and efficacy are of adequate level and the benefit-risk is established as being positive, then the vaccine gets approved and is ready to be commercialised and deployed,” says Dr Cavaleri.
How is it possible to develop a COVID-19 vaccine so quickly?
Normally, each stage of this process can take several years. But these are not normal times.
In the case of COVID-19, the goal is to apply greater flexibility, without compromising safety.
Researchers are currently looking at which parts of this process can be sped up, skipped or made more efficient. One method is to run different stages of the trial at the same time. Rapid procedures have also been implemented to accelerate regulatory steps.
“We have to differentiate between those tests that would be nice to have or supplementary, important information, but not critical, versus those testings that are still considered crucial in order to protect the safety of the participants in clinical trials”, says Dr Cavaleri.
According to the EMA, the first vaccines could be ready for approval at the beginning of 2021. However, the European regulator emphasises that only COVID-19 vaccines that prove their safety and efficacy will be approved.
“These vaccines will be given to millions of people and therefore their safety is crucial. We will only authorise vaccines if we have sound data allowing to establish their safety, efficacy, and quality”, the EMA told Dailyrater.
One way to speed up the vaccine development process is by sharing information and research between countries. The EU is pushing hard to increase scientific coordination in the fight against the coronavirus.
Is the vaccine approval process the same around the world?
The process of developing a vaccine is the same in Europe and other parts of the world. However, each jurisdiction has its own regulation and there may be some small differences in the way regulators interact with developers.
"Overall, there are no major differences and we are all following the same powerful requirements (for vaccine development) with, of course, some variation also on a case by case basis".
What if Europe doesn’t find the vaccine first?
The European regulator says it is open to accepting clinical trials conducted in other parts of the world. So if, for example, the United States or China finds the vaccine before Europe, it will not be necessary to repeat each step of the process, except for any tests that might be specific to the European population.
The EMA also states that Europe and North America are "pretty much aligned" in terms of manufacturing requirements.
“There is indeed intense cooperation with other regulators and in particular with the US Food and Drug Administration and with Canada,” says Dr Cavaleri.
Is the approval of a vaccine by the EMA valid for all EU member states?
If the EMA approves a vaccine, it applies immediately to all EU member states.
The only differences from one state to another are in terms of deployment and availability, as this will depend on the agreements made between the member states and the manufacturers.
Once a vaccine is approved, how long does it take to become accessible to everyone?
This depends on the capability of the developer to rapidly scale up the manufacturing after approval.
In the case of COVID-19, Dr Cavaleri claims that he has witnessed a significant effort among manufacturers to scale up quickly but it is still difficult to know if the early supply of any new vaccine will be sufficient to cover all of Europe's needs.