Coronavirus vaccines in general
When will life be back to normal? That is the one question that everyone in the world is asking.Tema
And it is a valid question; since the winter of 2019/20, the COVID-19 pandemic has affected populations all over the world. Millions have been infected, hundreds of thousands have died with COVID-19 disease, and the consequences of restrictions and precautions are huge. The COVID-19 pandemic has changed the way we live.
Vaccine development has been ongoing since the beginning of 2020, and everyone is hoping that the vaccines can help stop the spread of disease. The discussions about COVID-19 vaccines naturally raise a lot of questions, and in this theme, we try to answer some of them.
Here you can find more information about the COVID-19 vaccines that have been granted a conditional authorisation in the European Union and thus also in Denmark. Learn more about efficacy, the results of the trials based on which they were authorised, the package leaflet, the summary of product characteristics and questions and answers on the vaccine.
- Pfizer/BioNTech (Comirnaty)
- AstraZeneca (Vaxzevria)
- Johnson & Johnson - Janssen Pharmaceutical
Information from other authorities
The authorities’ joint website coronasmitte.dk
Danish Health Authority’s COVID-19 theme page
Statens Serum Institut (SSI): Monitoring of COVID-19 (in Danish only)
Danish Patient Safety Authority: Health risk, emergency preparedness and COVID-19 (in Danish only)
All stops have been pulled out to develop a vaccine as fast and possible without relaxing the requirements for documentation of efficacy and safety.
Researchers, vaccine manufacturers and governments are making every effort to ensure that corona vaccines can reach the public as fast as possible and mitigate the consequences of COVID-19.
Vaccine development is a complex and lengthy process normally taking up to 10 years. But because of the impact of COVID-19 on our society, the development is taking place faster than normal.
Development in the EU.
Development in the EU
The European Medicines Agency has mobilised extra resources and is assessing potential vaccines for COVID-19 while they are being developed. So-called rolling reviews are done in which the authorities review the documentation from the companies before all trials have been completed. In this way, a vaccine can be ready faster than normal. Read more about how the corona vaccines are assessed with a view to obtaining a potential authorisation here.
Through a concerted effort by the EU member states, the goal is to develop, assess and potentially authorise vaccines as fast as possible, with due regard to the same high standards and legal requirements for pharmaceutical quality, safety and efficacy as apply to all other medicines and vaccines.
From idea to authorisation
From idea to authorisation
Once an idea for a vaccine has formed, numerous tests must be conducted before the first vaccine dose of an authorised can be given. In vaccine development, there are different phases that researchers and companies must go through before the potential authorisation of the vaccine.
The researchers must first develop their vaccine candidates, which must then be tested in clinical trials. The more certain researchers become of the vaccine’s efficacy and side effects, the more people are given the vaccine for testing. You can read more about the clinical trial phases here. The phase 3 trials of the corona vaccines are very large, involving tens of thousands of trial subjects globally.
Emergency procedures launched: Ongoing assessment of trial data
The EMA has initiated an emergency plan, which implies that the review times can be shortened considerably and the experts of the EMA can review the documentation of the COVID-19 vaccines efficacy and safety fast without relaxing the authorisation requirements.
This is done through a so-called rolling review under which the vaccine manufacturers submit their data for assessment by the EMA’s experts as soon as they become available. In the normal authorisation procedure, the companies submit all data together after all tests have been completed. The rolling review means that the procedure can be completed in about 70 days compared to normally 210 days because the companies do not wait for all tests to have finished before submitting their data.
Accelerated Authorisation process for COVID-19 vaccines
To make COVID-19 vaccines available as fast as possible, a conditional authorisation can be granted. This basically means that a vaccine can be approved before the availability of long-term data on efficacy and side effects from completed phase 3 trials, which normally takes two to three years.
A conditional authorisation can only be granted if the experts of the EMA assess that the documentation of vaccine efficacy and safety is sufficiently solid, and if the benefits of making a vaccine available to people fast outweigh the theoretical risks of not having the same amount of long-term data as in a standard authorisation procedure.
Under a conditional authorisation, the vaccine manufacturer is obliged to submit further data to the EMA on an ongoing basis. A conditional authorisation is granted for one year and is subject to annual renewal. When the authorities have received all the agreed documentation, the conditional authorisation can be changed to a standard authorisation.
Accelerated manufacturing process
During the COVID-19 pandemic, the companies have expanded their production capacity and are starting productions BEFORE the vaccines are authorised. Consequently, these companies are running a risk since they cannot be sure that their vaccine will be authorised.
Historically many people participate in the COVID-19 vaccine trials. The vaccine manufacturers are responsible for ensuring that the design of the trials is such to provide sufficient documentation of the vaccines’ efficacy and side effects. The significance of the documentation depends, among other things, on the number of trial subjects and the duration of the trials. The trial subjects are also followed after vaccine authorisation.
This is the first time in the world that so many trial subjects over such a short period of time have participated in a vaccine trial. The trials are intended to generate knowledge about the vaccines’ effectiveness in COVID-19 prevention and to tell us if they are safe enough in fighting the disease.
When is the documentation of efficacy and safety sufficient?
It is up to the vaccine manufacturers to design the vaccine trials in a way that ensures the provision of enough documentation to demonstrate whether or not a vaccine works and establish the side effects it may cause, so that the drug regulatory authorities can authorise it.
if, for example, a group of 20,000 people are given the vaccine and another group of 20,000 people are given a placebo, it is possible to compare the number of COVID-19 infected individuals in the vaccinated group and placebo group, respectively, to learn more about how effectively the vaccine protects against infection.
This requires a certain number of COVID-19 infected individuals distributed between the group receiving (the right) vaccine and he group receiving a placebo in order to be sufficiently sure about the vaccine’s efficacy.
For example, it is not enough to document vaccine efficacy if a study shows that five vaccinated individuals in a group, despite being exposed to virus, do not contract COVID-19, whereas five individuals in the placebo group do get the disease. Had it been 150 individuals, the documentation would be far more solid.
One of the trials being performed right now has set the threshold for positive COVID-19 cases at 164. The positive COVID-19 cases are then checked against the list of those given the vaccine and those given a placebo. If all of the 164 positive COVID-19 cases are from the placebo group, and none are from the group receiving the vaccine, then the vaccine efficacy is 100 per cent.
How long should a clinical trial last?
There is no definitive answer to the question of how long a clinical trial should last. Aside from the number of people infected, it also depends on the consequences of waiting, of how effective the vaccine turns out to be, and on the side effects being identified during the trials.The longer a trial last, the more certain we become of a vaccine’s efficacy and side effects. In theory, we could wait for data from clinical trials for 10-15 years to reach a higher statistical confidence of efficacy and safety before authorising the vaccine. But in practice, society would have to handle the consequences of COVID-19 during this period.
The authorities therefore need to weigh the need for vaccinating the wider public against the documentation provided by the trials.
The trial subjects therefore continue to be followed in the time after a potential vaccine authorisation to become even more confident of the efficacy of the vaccine and to discover any potential side effects. A conditional authorisation is thus granted.
The vaccines for COVID-19 consist partly of protective ingredients and helping agents, which activate the body’s immune system and produce the antibodies that the body uses to attack coronavirus, and partly of stabilisers and in a few cases preservatives.
The protective ingredient is made up of antigens in the coronavirus vaccines; they are molecules in the form of proteins. It is the antigens in the vaccine that stimulate our immune system to produce antibodies to fight the targeted disease – in this case COVID-19.
The COVID-19 vaccines being developed use different technologies and contain different parts of the SARS-CoV-2 coronavirus.You can read more about the different types here
Helping agents boost the body's production of antibodies
Stabilisers and preservatives
The EU, including Denmark, is aiming for several COVID-19 vaccines at once. This includes vaccines that are based on different technologies. This is done to widen the opportunities for the rapid development, manufacture and dissemination of COVID-19 vaccines to all EU citizens.
Apart from the COVID-19 vaccines, most anti-virus vaccines usually consist of live attenuated virus like the chickenpox vaccine or inactivated dead virus like the regular seasonal influenza vaccine.
None of the COVID-19 vaccines being developed for the European market are based on live or inactivated virus. Instead, they are based on the special surface protein of the coronavirus, the so-called spike protein. Some of the vaccines contain the spike protein itself, while others contain the genetic code for the spike protein.
Illustration: Coronavirus with the red surface molecule called spike.
Other COVID-19 vaccines being developed contain inactivated coronavirus, like a regular influenza vaccine. These are developed in China, and they are not expected to enter the EU market.
Vaccines based on the special surface protein of the coronavirus
The purpose of these vaccine types is to stimulate the body to recognise the spike protein if we are exposed to coronavirus. In order for the body to recognise the spike protein, it must have met the spike protein before. There are several ways to achieve this:
- By being vaccinated with the spike protein itself (protein subunit).
- By being vaccinated with the genetic code for the spike protein, which is translated by the body and produces spike protein (mRNA and DNA vaccines).
- By being vaccinated with a modified virus (e.g. cold virus) in which the genetic code for the spike protein has been inserted, which is translated by the body and produces spike protein (virus vector).
The use of gene technology in COVID-19 vaccines
However, the genetic code for the spike protein is destroyed and is not stored in the body after vaccination. In addition, gene technology is already used to manufacture authorised and widely used vaccines, such as the hepatitis B and the HPV vaccines.
Safety and monitoring
The clinical trials of COVID-19 vaccines test the efficacy as well as the side effects. Although the development of the COVID-19 vaccines is faster than normal, the requirements for documentation of efficacy and safety are not relaxed. Once the vaccines are put into use, the authorities’ close monitoring will continue.
The monitoring of a vaccine continues for as long as it is in use. This applies to all medicines. The monitoring starts already in the early laboratory and animal tests, and it is intensified when the trials with human beings begin. Trials with humans, also called clinical trials, are divided into three phases so that the safety can be monitored closely and in a responsible manner.
The trials of the COVID-19 vaccines are the largest drug trials ever conducted in terms of the number of trial subjects. Tens of thousands of trial subjects have tested the vaccines for COVID-19 in trials all over the world. All trial subjects are followed closely, both during the trials and one year after the trials have ended.
In order for a vaccine to be authorised, the side effects must not be worse than the disease
Like all medicines, the COVID-19 vaccines can cause side effects. The decisive point is that the vaccine’s potential side effects must not be worse than the symptoms and the disease that the vaccine is intended to prevent. These two concerns are weighed up by independent experts of the European Medicines Agency in their assessment of whether the COVID-19 vaccines can be authorised.
Once authorised, the known side effects of a COVID-19 vaccine will appear from the package leaflet. Most vaccines may cause redness at the injection site or a mild headache that will pass after a few days.
Special monitoring of the safety after a vaccine has been authorised and taken into use
The Danish Medicines Agency registers, monitors and assesses reports of suspected side effects in Denmark. New vaccines and new medicine are monitored closely. This also applies to the COVID-19 vaccines. The Danish Medicines Agency, the Danish Health Authority and SSI have prepared for this specifically since a particularly high number of people are expected to be vaccinated within a short period of time.
In the first two years after a vaccine or medicine has been put in use, doctors, dentists, prescribing pharmacists and midwives must report any suspected side effects experienced by their patients to the Danish Medicines Agency. After this period, the reporting obligation only concerns suspected serious or unexpected side effects.
Other healthcare professionals, patients and relatives can report all suspected side effects to the Danish Medicines Agency. This applies to all medicines, including the COVID-19 vaccines.
Read more about side effects of COVID-19 vaccines here.
Vaccines are monitored throughout the EU
In the monitoring of the safety of COVID-19 vaccines, the Danish Medicines Agency collaborates with the drug regulatory authorities in Europe, the European Medicines Agency, EMA, and the World Health Organization, WHO, and more.
The drug regulatory authorities and the vaccine manufacturers report suspected side effects to the EMA, from which there is access to reports of suspected side effects in the entire EU/EEA and in third countries. The Danish Medicines Agency monitors and assesses in collaboration with other European drug regulatory authorities if there are signals of new or changed risks of the vaccines in the European database of side effects.
Joint European assessments of the safety of the vaccines will also be made in connection with the periodic safety update reports that vaccine manufacturers are obliged to submit at regular intervals.
Here the experts from the drug regulatory authorities in the EU member states assess if there is any new information that calls for changes to the package leaflet. The European Commission then considers the next steps.
If you are vaccinated against a disease, side effects such as redness at the injection site, fever and muscle soreness are common. Serious side effects could also occur, but they are rare. The authorities are keeping a close eye on the vaccines’ safety both before and after authorisation.
When you are vaccinated, you reduce your risk of contracting COVID-19 and falling ill. Like all medicines, the COVID-19 vaccines may cause possible side effects of which the most common are redness at the injection site and transient fever.
Before a vaccine is authorised, it is tested in large trials with tens of thousands of human subjects. The decisive matter for authorisation of a COVID-19 vaccine is that it protects against disease and that its possible side effects are not worse than the symptoms or the disease that it aims to protect.
Vaccines are monitored closely
Even though the COVID-19 vaccines have been developed faster than normal, the documentation has undergone the same thorough review. The trials of the COVID-19 vaccines are the largest drug trials the world has ever seen.
All of the experience with the vaccines has been gained over a shorter period of time than normal because the development steps have run in parallel. It cannot be ruled out that unexpected side effects may appear, but we know from other vaccines that almost all side effects after vaccination occur within the first six weeks and that it is very rare for them to occur later.
The drug regulatory authorities continue to monitor the vaccines closely after they have been authorised to be able to respond should it turn out that a vaccine is associated with an increased risk, such as side effects that did not emerge during the trials or known side effects that appear to occur more frequently than in the trials.
Vaccine monitoring includes side effects reported by the general public and healthcare professionals.
Healthcare professionals can report suspected side effects to the Danish Medicines Agency via this page Report an adverse drug reaction from human vaccines - for healthcare professionals (e-form), however, the form is in Danish only.
What to do after vaccination
Mild, transient side effects are common after any vaccination and most often completely harmless. This could be discomfort, redness at the injection site, mild fever and muscle soreness. There is no need to contact your doctor if you experience any of this. If you develop a mild fever this is a sign that your immune system is reacting.
Contact your doctor if you have serious symptoms
However, if you experience serious symptoms after vaccination, you should contact your doctor. This could be allergic reactions such as breathing difficulties or a rash. Your doctor can assess if the symptoms are caused by the vaccine or other conditions.
Your doctor is obligated to report suspected side effects to the Danish Medicines Agency. Remember that you can always ask your doctor if you are not sure whether the symptoms you have are side effects of the vaccine.
You or a relative can report suspected side effects to the Danish Medicines Agency via a Danish reporting form found here ’Meld en bivirkning ved COVID-19-vaccine - for borgere’ (Report a side effect from a COVID-19 vaccine – for members of the general public (e-form).
Contracts on vaccine procurement
The EU has assessed that joint procurement of COVID-19 vaccines is safest, quickest and most effective. This is because none of the EU member states alone have the required capacity to invest in the development and production of sufficiently many COVID-19 vaccines. In addition, the need to ensure that all EU member states have access to the vaccines is important.
The European Commission has therefore negotiated contracts with several vaccine manufacturers on the supply of vaccines, providing for all EU member states, including Denmark.
The EU finances part of the costs related to vaccine development to enable the vaccine manufacturers to develop a vaccine fast and to start a large-scale production. This is done to secure access to enough vaccines for those that the European health authorities recommend vaccination and for anyone else who wants to be vaccinated.
The objective in Denmark is to secure sufficiently many vaccine doses so that everyone who wants to be vaccinated can be.
Award criteria for vaccine procurement contract
The contracts negotiated between the European Commission and the vaccine manufacturers comprised a number of criteria that the manufacturers had to fulfil.
For example, the trials and studies conducted as part of the development of the vaccines must be designed so that it seems realistic that a useful result can be reached. The vaccine manufacturers were also assessed in terms of whether they had sufficient capacity to produce enough vaccines for the populations in Europe.
Read about which criteria the companies must fulfil, how the negotiations are conducted, and how the EMA safeguards against conflicting interest.
Overview of vaccine procurement contracts
The European Commission has signed contracts on the future procurement of vaccines that ensure the delivery of COVID-19 vaccines for Denmark
The European Commission is, on behalf of the EU member states, proceeding with negotiations with other vaccine manufacturers to secure the supply of vaccines. This is to ensure that there will be enough vaccines for everyone in case one or more of the vaccines cannot be authorised.
Corona vaccines are widely debated on social media. Please contribute to a factual debate, and by respecting the views that you don’t agree with.
Social media is overflowing with information about corona vaccines, and people have different views.
Regardless of our own beliefs, it is in everyone’s interest that we talk to each other and discuss questions about vaccines on an informed basis.
You are responsible for the information you share with others.
Remember the following general advice when using social media:
- Think before you share
- Check the sources
- Share substantiated information
- Don’t spread rumours
Show your respect for others – watch your tone
Tempers flare, especially on social media. We can make both social media and the world a better place when we treat each other with respect when we discuss our views.
A few tips for a proper vaccine debate on social media
- Make room for diversity
- Keep a civil tone
- Be open and curious about other people’s views
- Ask ‘what do you base this on?’
- Try to find trustworthy information and sources together
Further reading in Danish is available here:
Danish Emergency Management Agency: Use social media sensibly
Danish Medicines Agency: How to evaluate evidence of the efficacy of medicines
The Danish Medicines Agency’s corona virus theme about documentation