The medicine regulators from Australia, Canada, Singapore, Switzerland and the United Kingdom (Access Consortium) have discussed the regulatory evidence requirements for COVID-19 vaccine approvals and considerations for post-market pharmacovigilance. This collective statement on COVID-19 vaccines builds on the Consortium’s May 2020 pledge to work together to counter the COVID-19 global pandemic. We have updated this pledge to include the newest member of the Consortium, the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA).
Vaccination is one of the world's greatest public health achievements. Vaccines help prevent, control and even eliminate the spread of deadly diseases and save lives of millions of infants, children and adults. COVID-19 vaccines will play an important role in fighting the COVID-19 pandemic and, similarly to other vaccines, will be vital in national and global public health programs.
The Access Consortium members rigorously evaluate the totality of scientific and clinical evidence provided by sponsors of vaccines as well as other evidence available, including that which may be specific to our countries. Public health agencies develop vaccination programs, provide information about vaccines and immunization, and collaborate with regulators to monitor vaccine safety. Together, medicine regulators and public health agencies continue to monitor the safety of vaccines after they are approved for supply.
The medicines regulators within the Access Consortium will only authorise vaccines if their benefits outweigh the risks, based on the required high level of evidence provided by sponsors.
Authorised vaccines are continually monitored for safety, efficacy and quality.
Evidence of efficacy
Medicines regulators would ideally like to see vaccine efficacy that is as high as possible. A target efficacy of at least 50% is considered by some regulators, such as United States Food and Drug Administration (U.S. FDA), European Medicines Agency (EMA), and Health Canada, to be reasonable for COVID-19 vaccines. For a vaccine to be authorised, the sponsor must show that the vaccine prevents COVID-19 disease in well-conducted clinical trials in humans. Regulators will review the safety and efficacy of each vaccine on a case-by-case basis. Each jurisdiction will also consider the availability of other vaccines and treatments, the status of the pandemic and the epidemiology of disease in each regulatory jurisdiction.
Clinical trials should show that a candidate vaccine very significantly reduces the incidence of SARS-CoV-2 disease in people who are vaccinated, compared to a control group of people who don’t receive the vaccine. This should be based on a reduction in the rate of symptomatic laboratory-confirmed SARS-CoV-2 infections. Ideally, candidate vaccines should also reduce the transmission of disease between individuals, including from asymptomatic to uninfected individuals. A trial that has a sufficient number of participants who develop severe COVID-19 disease in the control group would provide relevant data to support that the vaccine is effective.
Evidence of safety
Clear evidence of safety is vital, especially considering the scale with which vaccines will be administered to help control the pandemic. Before a vaccine is authorized, sponsors must demonstrate robust evidence of safety. Regulators will monitor the continued evidence of safety of the vaccine.
Evidence of COVID-19 vaccine safety will require an adequate safety database to detect infrequent side effects. Participants in clinical trials must be followed for a median of at least 2 months after receiving their final vaccine dose. A longer follow-up period of 6 months for some trial participants is preferred to assess the potential risks of late-onset adverse events and vaccine-associated enhanced respiratory disease.
Participants in clinical trials should continue to be followed for at least 1 year and ideally longer to assess the duration of protection and longer-term safety of the vaccine. For proper assessment, the regulators will need access to the data from these follow-up studies, along with those from non-clinical studies, including studies assessing the risk of vaccine-associated enhanced respiratory disease.
Evidence of quality
Manufacturers of vaccines must follow good manufacturing practices (GMP) and provide sufficient data to demonstrate that the manufacturing process at each production site is well controlled and consistent. Data on established vaccine stability must also be provided before a vaccine can be authorised.
Monitoring safety and effectiveness (pharmacovigilance)
After a vaccine is authorised, sponsors will be required to conduct robust safety and effectiveness monitoring (pharmacovigilance) and risk minimisation activities. They will need to continuously monitor, assess and strengthen vaccine safety to ensure that the benefits of the vaccine continue to outweigh the risks.
Regulators collaborate in monitoring the safety and effectiveness of vaccines to assess new safety issues and take quick action to mitigate risks.
Overall, health care professionals, public health authorities, vaccine sponsors and regulatory agencies are to work closely together to monitor and assess the safety of COVID-19 vaccines after authorisation. Just as important, people who are vaccinated can also play a role in ensuring vaccine safety by immediately reporting any side effects to their health professionals.
Impact of initial vaccine approvals or emergency authorisations
Initial vaccine approvals or emergency authorisations may be based on interim analyses of ongoing randomised placebo-controlled phase 3 clinical trials. This may impact the continuation of these phase 3 clinical trials. For example, if a vaccine from a particular clinical trial is approved, participants in the clinical trial may want to know whether they received the vaccine or the placebo.
Despite initial approvals or emergency authorisations, industry sponsors, investigators and participants are encouraged to continue with their trials as planned. This will be key to providing robust evidence of long-term safety and protection against the virus, which may not be adequately demonstrated through post-authorisation surveillance studies. Data from fully completed and blinded placebo-controlled trials will be ideal to assess the long-term efficacy, safety, and durability of response to the vaccine. These data are also important as they will be used as a benchmark for ensuring that subsequent vaccines are safe and effective.