It's been a much quicker process than usual, but what's really changed?
Many people have indicated concern at the speed with which Covid-19 vaccines have been developed. Here we look in more detail at what's different this time around, and how safety standards have been upheld if not given greater focus as vaccines roll out to a global population.
How do we know that COVID-19 vaccines are safe and effective if they have been developed and tested so quickly?
In order to tackle COVID-19, pharmaceutical research organisations and companies have worked quickly to produce vaccines against the virus that causes COVID-19, but the speed at which these vaccines have been produced has become a matter of concern for some people, specifically in relation to safety and efficacy. Here we review what's different under Covid-19, and what's remained consistent with typical vaccine development process.
1. How long does it normally take for a vaccine to be developed?
The process of developing an entirely new vaccine is usually a long and very expensive one, often taking as long as 10 years, or more, from start to finish. It's rarely finished within 5 years. The process usually consists of the following stages:
Initial Development: new vaccines are developed in laboratories
Clinical trials: vaccines go through three phases of testing to make sure they are safe and effective
Manufacturing and Distribution
Vaccine tracking and safety monitoring[1]
2. How have vaccines against COVID-19 been developed so quickly?
Since the Ebola virus outbreak, scientists have been working on protocols to speed up vaccine development in the event of a dangerous pandemic[2]. There are three main reasons why COVID-19 vaccines have been developed so quickly, which are related to funding, vaccine design & technology, and logistics.
Funding
One of the main reasons COVID-19 vaccines have been developed so quickly is financial. There is global demand and real urgency for COVID-19 vaccines, with a strong motivation around the world to tackle the COVID-19 pandemic. Governments, public and private organisations have provided a lot of money, very quickly, towards the development of vaccines in a way we’ve not seen previously in any vaccine development. This has allowed pharmaceutical companies and research organisations to avoid some of the risks, financial concerns and barriers they typically face[3] that would slow them down. Normally, pharmaceutical companies and research organisations, like universities, have to apply for and collect funding for all stages of making a vaccine, from its initial development, through to all the clinical trials that need to be done to test its safety and efficacy. This means there are usually long waits between the different stages of vaccine development, as organisations wait to collect the funding necessary to move onto the next stage. With the funding for COVID-19 vaccines easily secured, pharmaceutical companies have been able to move rapidly throughout the different stages of vaccine development.
Design & Technology
Another reason why COVID-19 vaccines were developed so quickly relates to their design. Traditionally vaccines are developed using a weakened, inactive version, or a lab-produced portion of the virus. It can be a very time consuming process to create these types of vaccines. A lot of the COVID-19 vaccines, however, are made using different methods of delivering the genetic material of the virus into the body - known as “platform technologies”. For example, the Pfizer/BioNTech vaccine uses mRNA technology. This involves placing the genetic material of the SARS-CoV-2 virus (the virus that causes COVID-19) into an existing delivery platform. These delivery platforms were already being developed and researched for use in other vaccines before the COVID-19 pandemic[4]. Scientists didn’t have to take the time to develop the delivery system of the COVID-19 vaccines from scratch. The speed at which the mRNA vaccines were developed was supported by the pace with which specialists worked on the genetic code of the virus that causes COVID-19[5]. Having an existing delivery system, together with a rapid understanding of the virus’ genetic information, it has been possible to put together COVID-19 vaccines much faster than other vaccines in the past, which had to be developed from scratch.
Logistics
Finally, the process of testing the virus has also been carried out much more quickly than is normally possible. Usually, clinical trials happen in phases, carried out in sequence one after another:
Phase one - initial safety checks on a small number of people to make sure it is safe
Phase two - safety tests on more people, and initial efficacy checks to see if the vaccine is producing an immune response
Phase three - in a large efficacy trial, the vaccine is tested on thousands of people to prove it is effective at protecting people[6]
To streamline this process, many of the phases of clinical trials have overlapped, with trials occurring simultaneously. Once required safety criteria are met, the next phase of the trial can go ahead whilst the previous phase is being completed[7]. There is a misconception that making an effective vaccine has to take a very long time. In reality, what slows vaccine developments down are not the necessary scientific steps to make sure it is safe and effective, but real world logistical barriers, like financing. The research process can be long and requires much paperwork, from grant writing, waiting for funding windows, applying for funding, waiting for approval and recruiting volunteers etc. During the long process of developing a vaccine, only a portion of time is actually spent on the science and research to develop a successful vaccine[8].
Manufacturing was also able to start whilst vaccines were in the final phase of clinical trials so that they were ready for distribution immediately after they were approved. [9].
Clinical trials have also been able to proceed much faster than normal because it has been a lot easier to recruit volunteers for trials. To carry out clinical trials on vaccine safety and efficacy, researchers need to recruit volunteers from the public to take part in the trials. These are often poorly publicised and it can take months to recruit enough people to carry out the trials. Due to unprecedented global public support to tackle the pandemic, many people are more than willing to join trials. Researchers have been able to recruit enough volunteers to carry out their trials within a matter of days[10].
3. If mRNA vaccines are new, how do we know they are safe and effective?
Although platform technologies, like mRNA, are not as commonly used, it does not mean they are a completely new technology, or that they haven't been tested. The mRNA platform that the Pfizer vaccine uses has actually been in development by researchers at UK universities for over 20 years[11]. During this process, a safety profile of the vaccine delivery platform is developed, which allows for fast and cost-effective customisation of the delivery platform to develop new vaccines for different diseases.
4. If clinical trials are occurring so quickly, is safety being compromised?
Although clinical trials have moved much faster than usual because many financial and logistical barriers that vaccine developers usually encounter have been removed, the required steps to ensure safety have not been skipped. Once the required safety guidelines are met, clinical trials can move to the next phase, with a new phase starting as previous ones are completed. Although clinical trials have overlapped to speed up the process, no phases in clinical testing have been skipped. Results from clinical trials have shown the vaccines to be effective and they have not revealed any serious concerns after 8 weeks following vaccination[12][13][14].
5. But long term effects of the vaccine have not been tested, how do we know they are safe in the long run?
Clinical trials have focussed on testing for any safety concerns at or before around 8 weeks post-vaccination. Results did not find any serious adverse reactions to the vaccine that would be a cause for concern about vaccine safety within this time frame. Based on past research into vaccine safety following the development of hundreds and thousands of vaccines, it is very rare for vaccines to display any adverse effects after 8 weeks following vaccination. [15].
Furthermore, as vaccines are being rolled out to the public following clinical trials, continual vaccine safety monitoring is being undertaken globally. It is through this process that the rare but unfortunate blood clots associated with the AstraZeneca vaccine were identified. In this case, a small number of vaccinated individuals experienced blood clots after vaccination, and there were slightly more people than might typically experience a blood clot on a normal day without having been vaccinated. The surveillance systems in place were able to quickly identify this pattern. Experts were able to identify the medical conditions associated with these cases, which informed the subsequent guidance on the age categories for which this condition might be a risk, and alternative vaccines to be offered to people in those categories. Hong Kong was able to adapt its vaccination programme based on findings from global safety monitoring taking place in other countries.
The vast majority of patients report at most, mild side-effects, including pain and swelling in the arm where they were injected, feeling sick, headache, chills or fever. A small number of people might be allergic to vaccines but this is very rare. If someone has a history of being allergic to medicines they might be recommended against taking the vaccine until more is known about allergic reactions to vaccines. If allergic reactions do occur there are medications and treatments in hospitals that can deal with these effects, and patients are monitored in the immediate moments following vaccination because allergic reactions typically follow vaccination almost immediately[16].
There is a safety monitoring system of COVID-19 vaccines in place in Hong Kong. The Department of Health in Hong Kong, set up a “pharmacovigilance” system for the COVID-19 vaccines. This system is designed to receive reports of adverse events after vaccination and to identify any side-effects of the vaccines. Any adverse events are to be followed up, so the department has also appointed an “Expert Committee on Clinical Events Assessment Following COVID-19 Immunization, to provide an assessment of any reported adverse effects that might be linked to the COVID-19 vaccines. The Department of Health has also teamed up with the University of Hong Kong to conduct surveillance on any serious adverse effects that might be connected to the COVID-19 vaccines[17].
Since vaccines have been rolled out in Hong Kong, only a very small number of adverse effects following vaccination have been reported. As of May 2nd, only 0.2% of doses of the CoronaVac vaccine received by the public had any adverse events associated with them. The Comirnaty vaccine has even fewer associated adverse effects, 0.12% of all doses administered have reported adverse effects[18].
It is important to emphasise that medical professionals in Hong Kong are actively encouraged to report any potential adverse events, even if a connection to vaccination is highly doubtful, because the government is keen to exercise caution.
[1] CDC. (2021). Developing COVID-19 Vaccines. Centers for Disease Control and Prevention. Retrieved from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/distributing/steps-ensure-safety.html
[2] BBC. (2021). Oxford vaccine: How did they make it so quickly? BBC News. Retrieved from: https://www.bbc.co.uk/news/health-55041371
[3] The Guardian. (2021). How has a Covid vaccine been developed so quickly?. The Guardian. Retrieved from: https://www.theguardian.com/society/2020/dec/08/how-has-a-covid-vaccine-been-developed-so-quickly
[4] Live Sciences. (2021). COVID-19 vaccines: The new technology that made them possible. Retrieved from: https://www.livescience.com/mrna-vaccines-future-vaccine-development.html
[5] Asian Scientist. (2020). Chinese Scientists Sequence Genome Of COVID-19. Retrieved from: https://www.asianscientist.com/2020/02/topnews/china-coronavirus-covid-19-study/
[6] BBC. (2021). Oxford vaccine: How did they make it so quickly? BBC News. Retrieved from: https://www.bbc.co.uk/news/health-55041371
[7] GOV.UK. (2021). COVID-19 vaccine development timeline. Retrieved from: COVID-19 vaccine development timeline
[8] BBC. (2021). Oxford vaccine: How did they make it so quickly? BBC News. Retrieved from: https://www.bbc.co.uk/news/health-55041371
[9] CDC. (2021). Developing COVID-19 Vaccines. Centers for Disease Control and Prevention. Retrieved from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/distributing/steps-ensure-safety.html
[10] The Guardian. (2021). How has a Covid vaccine been developed so quickly?. The Guardian. Retrieved from: https://www.theguardian.com/society/2020/dec/08/how-has-a-covid-vaccine-been-developed-so-quickly
[11] Live Sciences. (2021). COVID-19 vaccines: The new technology that made them possible. Retrieved from: https://www.livescience.com/mrna-vaccines-future-vaccine-development.html
[12] Polack, F. P., Thomas, S. J., Kitchin, N., et al. (2020). Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine, The New England Journal of Medicine, 383: 2603-2615. Retrieved from: https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
[13] Wu, Z., Hu, Y., Xu, M., et al. (2021). Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infectious Diseases. https://doi.org/10.1016/ S1473-3099(20)30987-7
[14] CDC. (2021). Developing COVID-19 Vaccines. Centers for Disease Control and Prevention. Retrieved from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/distributing/steps-ensure-safety.html
[15] CDC. (2021). Developing COVID-19 Vaccines. Centers for Disease Control and Prevention. Retrieved from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/distributing/steps-ensure-safety.html
[16] CDC. (2021). Developing COVID-19 Vaccines. Centers for Disease Control and Prevention. Retrieved from: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/distributing/steps-ensure-safety.html
[17] Drug Office. (2021). Safety Monitoring of COVID-19 Vaccines in Hong Kong. Gov.HK. Retrieved from: https://www.drugoffice.gov.hk/eps/do/en/doc/Safety_Monitoring_of_COVID-19_Vaccines_in_Hong_Kong.pdf
[18] Drug Office. (2021). Safety Monitoring of COVID-19 Vaccines in Hong Kong. Gov.HK. Retrieved from: https://www.drugoffice.gov.hk/eps/do/en/doc/Safety_Monitoring_of_COVID-19_Vaccines_in_Hong_Kong.pdf