Ten things pharmacists should know about COVID-19 vaccines

1. Three COVID-19 vaccines have now been approved for use in the UK

On 2 December 2020, the Pfizer/BioNTech mRNA vaccine became the first COVID-19 vaccine to be authorised for temporary supply across the UK. The UK had already ordered 40 million doses, meaning administration of the vaccine, to the highest priority groups, could start on 8 December 2020.

On 30 December 2020, the Oxford/AstraZeneca adenoviral vector vaccine became the second COVID-19 vaccine to be authorised for use in the UK. The government has secured access to 100 million doses of the Oxford/AstraZeneca vaccine and the first patient, an 82-year-old dialysis patient, was vaccinated on 4 January 2021.

On 3 January 2021, the Moderna mRNA vaccine, which had already been granted a conditional marketing authorisation in the EU, became the third COVID-19 vaccine to be authorised for use in the UK. The government had agreed to purchase an additional 10 million doses of the Moderna vaccine on top of its previous order of 7 million, taking the total number of doses to 17 million. Doses of the vaccine will be available in the UK from spring 2021.

Developers of the other COVID-19 vaccines in the UK portfolio are hoping to achieve regulatory approval in early to mid-2021.

On 1 December 2020, the European Medicines Agency (EMA) said it was starting a rolling review to speed up the assessment of Janssen’s Ad26.COV2.S COVID-19 vaccine. On 12 January 2021, it said that it had received an application for conditional marketing authorisation of the Oxford/AstraZeneca vaccine.

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 50 in clinical trials^[1].

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 were approved for use before phase III results were released, but not in the UK

Three vaccines, two adenoviral vector vaccines and a protein-based vaccine, 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.

On 14 October 2020, Russia registered its second COVID-19 vaccine. Developed by the State Research Center of Virology and Biotechnology, in Russia, the EpiVacCorona vaccine completed its early stage human trials in September 2020 and phase III trials are planned to start in November or December 2020.

On 3 January 2021, India announced that it had granted an emergency approval to a locally-produced COVID-19 vaccine, Covaxin, without peer reviewed phase I/II results and an incomplete phase III trial, which has raised concerns among experts. Efficacy data is not expected until February 2021.

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 367 million doses of different vaccines from seven manufacturers. The portfolio includes two adenoviral vector vaccines (Oxford/AstraZeneca and Janssen), two mRNA vaccines (BioNTech/Pfizer and Moderna), 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.

On 29 November 2020, UK government announced that it had signed a deal for a further 2 million doses of Moderna’s vaccine candidate, bringing the total to 7 million doses for the UK.

On 3 January 2021, the UK government confirmed that it had agreed to purchase an additional 10 million doses of the Moderna vaccine on top of its previous order of 7 million, taking the total number of doses to 17 million.

5. Five of the seven vaccines being backed by the UK are already in phase III trials

Moderna, which is conducting a phase III trial involving 30,000 participants over 18 years of age in the United States, announced primary efficacy results of 94.1% on 30 November 2020. No significant safety concerns were reported. Moderna announced on 10 December 2020 that it had dosed the first participants in a phase II/III study of its vaccine in 3,000 adolescents aged 12 years to 17 years.

Interim analysis of pooled data from phase II/III trials of the Oxford University/AstraZeneca ChAdOx1 vaccine, published in the Lancet on 8 December 2020, suggested it is up to 90% effective in preventing COVID-19 symptoms.

In the trials, which involved more than 24,000 participants from diverse racial groups, the vaccine was given in two regimens: two full doses, or a half dose followed by a full dose. In the full dose/full dose arm, which involved 8,895 participants, the vaccine prevented 62% of cases, and in the half dose/full dose arm, which included 2,741 participants, it prevented 90% of cases, giving an overall efficacy of 70.4%.

The results of Pfizer/BioNTech’s vaccine phase II/III study, published in The New England Journal of Medicine on 11 December 2020, suggested that a two-dose regimen of BNT162b2 conferred 95% protection against COVID-19 in persons 16 years of age or older, at least 7 days following the second dose.

The study included around 43,000 people, aged 16 and older, who were randomised to receive two doses of either the BNT162b2 vaccine or placebo, 21 days apart. Protection began around 12 days after the first dose, with an efficacy of 52% between doses. This particular study did not examine whether vaccination prevented asymptomatic infection.

The paper also highlighted that the safety of the vaccine, over a median of two months, was similar to that of other viral vaccines.

Novavax’s protein adjuvant vaccine began phase III UK trials in September 2020. It recruited over 15,000 participants from 35 research UK sites in just over two months; 50% of volunteers were given two intramuscular doses, 21 days apart, while the remaining received a placebo.

On 29 January 2021, interim analysis of phase III data suggested that the vaccine was 89.3% effective at preventing COVID-19, including effectiveness against the new variants of concern.

Also on 29 January 2021, Janssen Pharmaceutical Companies of Johnson & Johnson announced that an interim analysis of phase III clinical data for its adenoviral vaccine suggested it was 66% effective at preventing the study’s combined endpoints of moderate and severe COVID-19 at 28 days post-vaccination among all volunteers, including those infected with an emerging viral variant.

The vaccine, called Ad.26.COV2.S or JNJ-78436725, requires only a single injection and can be stored in a refrigerator for months.

A separate phase III trial of a two-dose regimen is being conducted in parallel in multiple countries.

6. Once a vaccine is approved in the UK, its administration will be prioritised according to age and clinical risk

Following the approval of the Pfizer/BioNTech vaccine, Wei Shen Lim, chair of COVID-19 immunisation within the Joint Committee on Vaccination and Immunisation (JCVI), said that age was the “single most important factor” in prioritising groups that would be vaccinated in the first phase of the vaccination programme.

Priority groups for the first phase of the vaccination programme are:

1. Residents in a care home for older adults and their carers
2. All those aged 80 years and over and frontline health and social care workers
3. All those aged 75 years and over
4. All those aged 70 years and over and clinically extremely vulnerable individuals
5. All those aged 65 years and over
6. All individuals aged 16 years to 64 years with underlying health conditions which put them at higher risk of serious disease and mortality.
7. All those aged 60 years and over
8. All those aged 55 years and over
9. All those aged 50 years and over

Lim said that the vaccine would be offered on a voluntary basis but that, in the first phase of the vaccination programme, he hoped that “90–99% of people who are at risk of dying from COVID-19 will be included or covered”.

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^[2].

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^[3]. 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.

On 31 December 2020, the Joint Committee on Vaccination and Immunisation (JCVI) published a short statement saying that it supported a two-dose vaccine schedule for both the Pfizer/BioNTech and Oxford/AstraZeneca vaccines, advising a maximum interval between the first and second doses of 12 weeks for both vaccines.

The JCVI said it could be assumed that protection from the first dose would wane in the medium term, and the second dose will still be required to provide more durable protection, but it advised initially prioritising delivery of the first vaccine dose as this was highly likely to have a greater public health impact in the short term and reduce the number of preventable deaths from COVID-19.

8. Pharmacists will be able to administer an unlicensed COVID-19 vaccination when one becomes available

This is following changes to the Human Medicine Regulations (HMR) that came into effect from 16 October 2020, following a government consultation on the delivery of COVID-19 and flu vaccines using a wider workforce, potentially including pharmacy technicians.

In its consultation response, published on 16 October 2020, the Department of Health and Social Care (DHSC) said national protocols would be created in each of the UK’s four countries to determine who could administer any COVID-19 or flu vaccine, and these should include requirements for supervision by an additional experienced vaccinator for healthcare staff newly qualified to administer vaccines.

Hospital pharmacists working in vaccination centres and hospital hubs have been given the “lead responsibility” for ensuring COVID-19 vaccines are safely handled and administered. A letter sent earlier in December 2020 from Keith Ridge, chief pharmaceutical officer for England, said a “lead responsible chief pharmacist” should be appointed for each hospital hub or vaccination centre.

The programme will start in hospital hubs from 8 December 2020, with the vaccination of outpatients aged 80 years or over who are already planning to visit hospitals, inpatients in the same age group who are being discharged home, and care home workers.

Fifty hospitals have been chosen by NHS England to be hubs, where vaccinations will take place on site.

In a letter sent to contractors on 27 November 2020, NHS England said it was planning for designated pharmacy sites to be ready to administer COVID-19 vaccines under a local enhanced service (LES) from late December 2020 or early January 2021.

However, NHS England said in the letter that it only plans to “commission selected community pharmacy contractors” who are able to deliver vaccines from a site that meets a specific set of requirements — outlined in a separate document — which include “fridge space to store (2–8ºC) 1,000 vaccine doses at one time”.

Selected pharmacies will be paid £12.58 per vaccination. If two doses per patient are required, a payment of £25.16 will be made on completion of the final dose.

It is likely that only a few community pharmacies will have the storage facilities and staffing to act as vaccination sites, at least in the first phase of the programme.

Primary care networks will also start running local vaccination services from 14 December 2020.

The first wave of 200 sites run by community pharmacies are due to start administering vaccines from the week commencing 11 January 2021.

NHS England has yet to confirm the total number of pharmacy-led vaccination centres. However, Prime Minister Boris Johnson told Parliament on 6 January 2021 that “hundreds” had been commissioned to provide vaccinations.

As of 28 January 2021, 117 community pharmacies were administering vaccines across the country, with around 200 expected to join the programme.

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.

Pfizer/BioNTech’s vaccine must be stored at -70°C, however, once thawed, it can be stored for 5 days at 2-8 degrees C but, once out of the refrigerator, it needs to be used within 6 hours.

Whereas Moderna’s vaccine can be stored at standard freezer temperatures of -20°C and is stable for 30 days in a refrigerator.

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 Oxford/AstraZeneca vaccine can be kept at 2-8°C at all times. However, once opened, it needs to be used within 6 hours when stored at room temperature and within 48 hours when stored in a refrigerator.

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^[4].

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^[5]. 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^[6].

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^[5].