The development of a vaccine is a complex, long process that historically has taken around 10-15 years, so is it right that people are concerned as to how quickly the vaccines against COVID-19 have been developed and made available?
A vaccine is a mechanism to ‘train’ the body’s immune response. Once vaccinated, if a person comes into ‘contact’ with the actual virus (or bacterium), their immune system will ‘remember’ it. In turn, that person will not develop an infection, or develop a milder form of the infection.
Before a vaccine becomes available in any country, it must first undergo rigorous testing and evaluation. This ‘preclinical’ phase does not involve testing on humans but the experimental vaccine is given to animals after extensive lab research, to ensure that the immune response is triggered, and to evaluate its safety. If the vaccine triggers the required immune response, it is then tested in humans.
Many candidate vaccines never progress beyond this stage.
There are three phases of clinical trials – each of which has to follow strict standards set down by medicines regulators:
Phase 1: This phase aims to test the safety of the vaccine, takes around 2 years and requires approximately 10-50 (healthy) people.
Phase 2: Building upon the results of the Phase 1 study, this phase aims to further characterise and understand the immune response, safety and dosage regimen. This stage typically takes 2-3 years and involves hundreds of people in randomized trials (including a placebo (control) group and people with the target disease.
Phase 3: This phase is concerned with assuring that the vaccine safely protects against the disease, including the prevention of infection and the immune response. This stage often takes longer (5-10 years) and requires several thousands of people to participate in the trial.
At any point in the clinical trial setting, a candidate vaccine may be ‘withdrawn’ due to safety or efficacy concerns. These patients would then be monitored post-study to ensure their ongoing safety.
Once the required data is generated from the pre-clinical and clinical trial settings, and assuming the data adheres to the required safety, efficacy and quality standards, this is then submitted and scientifically reviewed by the regulatory authorities to gain approval.
This step alone can take 6-9 months.
Once approved, then it still does not mean that the vaccine is immediately available – the vaccine has to be produced on a mass scale, and then it has to be distributed at the country-level.
So, how did we get a COVID-19 vaccine approved in the UK in December 2020, when it was only considered a pandemic in March 2020?
Well, the first reason is that we were not starting from scratch, scientists had been studying coronaviruses for years. Depending on your source, potentially scientists have been studying coronavirus since the 1930s! This meant, however, that scientists were already familiar with the viral structure, the genomic make-up and lifecycle of the virus. This meant that initial pre-clinical work was vastly accelerated to other vaccine candidates.
The AstraZeneca and Pfizer vaccines also leveraged an existing mRNA vaccine platform technology to enable rapid development, and this in turn enables scientists to become more familiar with the safety profile of the vaccine candidate earlier on.
The third reason can be attributed to the financial investments – suddenly this became a global problem and the governments in different countries invested earlier on, which is quite atypical when it comes to routine vaccine development.
Another consideration is that while in traditional vaccine development the phases of clinical trials are generally carried out in sequence, in the case of the Covid vaccines they have overlapped. This made the process faster and the recruitment of patients for these trials was also accelerated. (The Pfizer clinical trial involved an excess of 40,000 patients and the AstraZeneca study, over 20,000 patients).
Recruitment can often take many weeks/several months whereas this happened much more rapidly – thanks to the power of social media.
In addition, unlike the usual waterfall method of submitting all the documentation at the end of the Phase 3 trial, the regulators supported the approach of a “rolling review” of data – with information being released to the regulators once it had been obtained. This was a gamble for the companies involved as at any stage the data may have suggested a negative benefit-risk profile and the vaccine could have failed, which would have been very costly to the companies had this occurred.
Finally, the vaccine manufacturing began in parallel, again another huge risk to those involved.
Does it mean the companies/regulators have cut-corners since the vaccine has been developed in a shorter time-frame than other vaccines?
The simple answer is no. The required steps and rigorous testing was still performed, just in a different way. The same data sets were reviewed by the independent scientific experts (regulators), and the results adhere to the required safety, efficacy and quality standards as would have been done for any other vaccine.
Yes, there was a few early reports of severe allergic reactions with the Pfizer vaccine but the advice was quickly updated to reflect that people with a previous history of severe allergic reactions to any of the ingredients of the vaccine should not receive it, and anyone receiving the vaccine needs to be monitored for at least 15 minutes afterwards. We have now much more extensive data, and this is very rare as are any other serious reactions to the vaccine.
There are of course unknowns – for instance the long-term safety or effectiveness long into the future. This is the case for all other vaccines (and medicinal products), that are developed – there will always be unknowns and every company/regulatory has the ongoing obligation to continually ensure the safety and efficacy of products by ongoing studies and routine pharmacovigilance monitoring activities.
So far, in our vaccination programme (>20 million people have had their first dose in the UK), the overwhelming majority of concerns related to injection-site reactions (sore arm) and generalized flu-like symptoms. These are found to happen shortly after the vaccination and are typical reactions reflecting the normal immune response expected from a vaccine.
The vaccine is part of an ongoing programme to manage this virus, and until we are on a similar level globally (in terms of infection rates/vaccinations), and until we have even more data on some of the unknowns, we still need to take extra precautions. These include wearing a mask when around others, practising social distancing, frequent handwashing and avoiding crowded areas/poorly ventilated indoor areas.
Covid-19 has taken too many lives, too early (in the UK this is more than 120,000 people within 28 days of a positive test). Based on current experience, the expected benefits of vaccination in preventing the infection far outweigh any known side-effects.
Should anything change this, this would be addressed immediately.
Trust the experts. Save lives.