Ten things pharmacists should know about COVID-19 vaccines
Work towards a COVID-19 vaccine is progressing rapidly and new information is emerging every day. Here we aim to summarise the most important details of COVID-19 vaccine development from a pharmacy perspective.
Open access article
The Royal Pharmaceutical Society has made this article free to access in order to help healthcare professionals stay informed about an issue of national importance.
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1. The first COVID-19 vaccines could be approved for use in the UK in early 2021
Matt Hancock, the health secretary, has said that a vaccine may be available by late 2020, or early 2021. However, before anyone can predict when we might have a useable vaccine against COVID-19, efficacy results from phase III trials — which are currently in progress — are needed. And, if positive, these need to be presented to the appropriate regulatory authority to authorise emergency use.
Developers of several vaccines, including those in the UK portfolio, are hoping to achieve regulatory approval in early to mid-2021. In early October 2020, the European Medicines Agency said it was starting a rolling review to speed up the assessment of two vaccines for COVID-19 — the ChAdOx1 vaccine being developed by Oxford University and AstraZeneca, and the BNT162b2 vaccine being developed by BioNTech and Pfizer.
However, once a vaccine is approved, manufacturers then need to ensure there is enough of it in the freezer, ready to go, as well as the manpower and facilities to deliver it fairly to billions of people across the world.
The World Health Organization says it does not expect widespread dissemination of a COVID-19 vaccine until the middle of 2021 at the earliest.
Calculations by the Coalition for Epidemic Preparedness Innovations show that, even if manufacturing capacity doubled, as planned, over the next 12 months, less than half the world’s population could be protected against COVID-19 by the end of 2022.
2. There are currently more than 300 COVID-19 vaccine candidates
However, the majority of these are at the pre-clinical phase of development, with around 40 in clinical trials.
Only phase III trials can determine if the vaccine protects against COVID-19. Many phase III vaccine studies fail because the dose chosen does not best balance safety and efficacy, and because they are large enough to reveal evidence of relatively rare side effects that might be missed in earlier, smaller-scale studies.
If there is sufficient evidence to demonstrate the safety, quality and efficacy of a vaccine against COVID-19, a temporary authorisation for the supply of the vaccine could be given by the UK’s licensing authority, under regulation 174 of the Human Medicines Regulations, before the vaccine is officially licensed. The government is currently ensuring the right legislative measures are in place to deal with that scenario.
Based on previous vaccine development, those at the pre-clinical stage have roughly a 7% chance of succeeding, while those that make it to clinical trials have about a 20% chance of succeeding.
More than 250,000 people in the UK have signed up to take part in COVID-19 research
One way in which development of COVID-19 vaccines has been accelerated is by combining clinical research phases, so some vaccines have undergone, or are currently undergoing, phase I/II or phase II/III trials.
So far, more than 250,000 people in the UK have signed up to take part in COVID-19 research through the NHS COVID-19 vaccine research registry.
3. Some COVID-19 vaccines have already been approved for use, but not in the UK
Two adenoviral vector vaccines have been given early or limited approval without waiting for the results of phase III trials.
Sputnik V — a combination of two adenoviruses, Ad5 and Ad26, formerly known as Gam-COVID-Vac — which is being developed by the Gamaleya Research Institute in Moscow, Russia, was approved by the Ministry of Health of the Russian Federation on 11 August 2020.
Experts have raised considerable concerns about the vaccine’s safety and efficacy, given it has not yet entered phase III clinical trials. However, Russia has said the approval is a “conditional registration certificate”, which would depend on results from phase III trials.
Another vaccine developed by the Chinese company CanSino Biologics, which is based on the adenovirus Ad5, was approved by the Chinese military in June 2020 for a year as “a specially needed drug”. In August 2020, the company announced that it plans to start phase III trials of its vaccine in Russia.
4. The UK has pre-ordered the most COVID-19 vaccines per capita in the world, with enough for five doses per person
The UK is hedging its bets, with pre-orders for 340 million doses of different vaccines from six manufacturers. The portfolio includes two adenoviral vector vaccines (Oxford/AstraZeneca and Janssen), an mRNA vaccine (BioNTech/Pfizer), an inactivated whole virus vaccine (Valneva), and two protein adjuvant vaccines (GSK/Sanofi, Novavax). The government has also provided £41m in funding to support trials of another RNA vaccine being developed by Imperial College London. Find out more about their development here.
A ‘portfolio-based’ approach will allow the government to ‘monitor the landscape of coronavirus vaccine development’
According to a government spokesperson, this “portfolio-based” approach will allow the government to “monitor the landscape of coronavirus vaccine development”, both in the UK and internationally, and ensure that the UK is in the best position possible to support the discovery, manufacture and mass-deployment of a successful vaccine.
Efforts to find and manufacture a safe and effective vaccine against coronavirus are being led by the Vaccine Task Force, which was set up by the Department for Business, Energy and Industrial Strategy in May 2020.
The UK has also committed to join the COVID-19 vaccine allocation plan — COVAX — an international initiative, co-led by the World Health Organization, to support discovery, manufacture and fair distribution of COVID-19 vaccines worldwide.
5. Four of the six vaccines being backed by the UK are already in phase III trials
This includes the Oxford University/AstraZeneca ChAdOx1 adenoviral vector vaccine, which is undergoing phase III clinical trials in South Africa, Brazil and the United States, as well as phase II/III trials in the UK. The UK trial involves 10,000 adults and children.
Results from the phase I trial of ChAdOx1, published in The Lancet, show that it is safe and invoked an immune response, but this is not the same as showing efficacy.
Novavax’s protein adjuvant vaccine began phase III UK trials in September 2020, with 10,000 adults aged 18–84 years, with and without relevant comorbidities.
Also in September 2020, Janssen launched phase III trials of its adenoviral vector vaccine. One trial will test a single-dose regimen across three continents, involving up to 60,000 adults, with and without comorbidities. A separate phase III trial of a two-dose regimen in multiple countries will be conducted in parallel.
BioNTech and Pfizer are carrying out phase II/III trials of their RNA vaccine with more than 25,000 volunteers in the United States, Argentina and Brazil.
6. Once a vaccine is approved in the UK, its administration will be prioritised according to age and clinical risk
In September 2020, the Joint Committee for Vaccination and Immunisation (JCVI), which advises UK health departments on immunisation, said that a simple, age-based programme would likely result in faster delivery and better uptake in those at the highest risk from COVID-19. It produced a “provisional” ranking of prioritisation for persons-at-risk:
- Older adults resident in a care home and care home workers
- All those aged 80 years and over and health and social care workers
- All those aged 75 years and over
- All those aged 70 years and over
- All those aged 65 years and over
- High-risk adults aged under 65 years
- Moderate-risk adults aged under 65 years
- All those aged 60 years and over
- All those aged 55 years and over
- All those aged 50 years and over
- Rest of the population (priority to be determined)
However, the JCVI said that the prioritisation could “change substantially” if the first available vaccines were not considered suitable for, or effective in, older adults.
7. It is unlikely that one vaccine will be suitable for all sectors of the population, and booster doses may be needed
Much like influenza vaccines, it is likely that we will need different types of COVID-19 vaccines for different sectors of the population. For example, there is little evidence of the safety of RNA vaccines in children and pregnant women, whereas the protein–adjuvant platforms have long experience in children.
Older adults are both more susceptible to severe COVID-19 and less likely to mount an immune response following vaccination
Older adults may be particularly problematic as they are both more susceptible to severe COVID-19 and less likely to mount an immune response following vaccination, because of an ageing immune system.
There are also concerns that some people may already have immunity to the vectors used in adenoviral vector vaccines, which may end up hampering — or even neutralising — the new vaccines. However, the adenoviral vectors being used in vaccines within the UK portfolio have been designed to overcome this problem.
In addition, it is not yet known how long the vaccine-induced protection may last in humans, and it remains possible that booster vaccinations will be required to sustain protection against COVID-19. The need for boosters is likely to influence the choice of vaccine platform used since immunity induced by a first dose of viral vector vaccine may make them unsuitable for a booster dose, meaning that a combination of different vaccines is required.
Even then, the first generation of COVID-19 vaccines may only be partially effective — flu vaccinations, for example, are only 40–60% effective. The World Health Organization gives a target efficacy for SARS-CoV-2 vaccines of at least 50% (preferably 70%), including in older people.
The effectiveness of a vaccine can be influenced by how it gets into the body. All of the first-wave vaccines that are now in clinical trials have to be injected into muscle. A spray, similar to that used to deliver asthma medicines, might work better, since the coronavirus invades our bodies through the airway. This approach is currently being investigated in small trials to assess the safety and effectiveness of Oxford University’s adenoviral vector vaccine and Imperial College London’s RNA vaccine.
Ultimately, rigorous testing is required across all populations to make the careful decisions needed for vaccine development and eventual delivery.
8. Pharmacists and their teams are likely to be involved in administering COVID-19 vaccines once they are available
The government has proposed expanding the scope of patient group directions to allow pharmacists to administer unlicensed vaccines, including the COVID-19 vaccine. There may also be scope for pharmacy technicians to become eligible to administer a COVID-19 vaccine as the government has proposed a national protocol to allow registered healthcare professionals, who do not normally vaccinate, and people who are not registered healthcare professionals, to safely administer a licensed or temporarily authorised COVID-19 vaccine.
The proposals have been widely welcomed by health bodies, but the Royal Pharmaceutical Society (RPS) has called for indemnity insurance for individual healthcare professionals to be amended to cover the administering of unlicensed vaccines.
The RPS highlighted that European legislation to provide blanket indemnity for all healthcare professionals delivering COVID-19 vaccination services is being considered, but that clarity is needed on how this would apply to UK healthcare professionals once we exit the EU.
The consultation for the government’s proposals closed on 18 September 2020.
Four of the six vaccines in the UK portfolio require two doses, several weeks apart, with single and two-dose regimens being tested in trials of the other two vaccines. The need for a second dose may further complicate delivery of mass vaccination programmes.
9. Cold storage may be a challenge as some vaccines need to be stored at -80°C
There are some concerns that, depending on the COVID-19 vaccines that make it through to approval, there may be challenges associated with shipping and storage of the vaccine.
RNA vaccines will need to be shipped on dry ice and stored in ultra-cold freezers
For example, mRNA is naturally unstable and needs to be stored frozen at below -20°C, and in some cases as cold as -70–80°C. This will complicate the global shipping and clinical use of RNA vaccines, especially in the developing world, since they will need to be shipped on dry ice and stored in ultra-cold freezers until just before use.
Imperial College London, which is developing an RNA vaccine, has said that although, initially, its vaccine will be a frozen product, it will look to rapidly transition to a 2–8°C presentation, with a freeze-dried product as a longer-term option.
Some vaccines, including the adenoviral vector vaccines, adjuvanted protein vaccines and inactivated whole virus vaccines , are expected to be stable at 2–8°C, so storage for those will be the same as for influenza vaccines.
The UK government is taking a number of steps to help bolster its vaccine manufacturing capacity. In May 2020, it announced that it was investing up to £93m to open the UK’s first dedicated Vaccine Manufacturing and Innovation Centre (VMIC), 12 months early, in summer 2021. While the VMIC is being built, a rapid deployment facility has been established with a further investment of £38m, to begin manufacturing in 2020.
The government has also made several other deals, including one with the Indian pharmaceutical company Wockhardt, in which the company has agreed to carry out the “fill and finish” stage of the manufacturing process, whereby the vaccine is dispensed into vials ready for distribution. Wockhardt has a manufacturing capacity of 400 million doses in the UK.
In addition, several of the main vaccine developers have made deals with manufacturers in different countries to secure sufficient capacity. For example, AstraZeneca, which has partnered with Oxford University on its vaccine, has reportedly made deals with more than 20 contract manufacturing organisations to hit its goal of delivering 2 billion doses by the end of 2021.
10. At least 60% of the population would have to be immune to achieve herd immunity, which could take years
Herd immunity describes the process by which at-risk individuals are protected from infection because they are surrounded by immune individuals, therefore minimising spread of the virus.
Public health strategies to control COVID-19 generally fall into two categories: ‘mitigation’, which aims to achieve herd immunity by allowing the virus to spread through the population while mitigating disease burden so as not to overwhelm the health service, and ‘suppression’, which aims to drastically reduce SARS-CoV-2 transmission rates and halt endogenous transmission in the target population.
Achieving widespread herd immunity in the UK would mean that 36 million people will need to be immune
Estimates suggest that achieving widespread herd immunity in the UK would mean that 36 million people will need to be immune, either through getting infected and recovering, or by receiving a vaccine. Herd immunity becomes harder to achieve when vaccine-induced or natural immunity is partial or only for a limited period, or when logistical or other constraints limit roll-out or uptake of a vaccine.
Experts say that minimising the spread of COVID-19 by practising hand hygiene and social distancing is the only method we currently have to reduce the number of people dying of the infection.
Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2020.20208429
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