Regulations 174A and 247A: one-year review
Published 5 April 2022
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1. Introduction
The Human Medicines (Coronavirus and Influenza) (Amendment) Regulations 2020 were laid in Parliament on 16 October 2020. The amendments made included the addition of regulation 174A (R174A) that allows for conditions to be attached to the temporary authorisations of an unlicensed medicine, such as a COVID-19 vaccine, and regulation 247A (R247A) that allows for the expansion of the workforce legally able to administer a COVID-19 or influenza vaccine under an approved national protocol and allows vaccinations to happen on sites other than registered pharmacies, subject to the conditions set out in the protocol.
These amendments followed a public consultation held from 28 August to 18 September 2020 on changes to the Human Medicines Regulations 2012 to support the rollout of COVID-19 vaccines and the upscaling of the influenza vaccination programme in the UK.
As a result of the responses received, the Department of Health and Social Care (DHSC) made key changes to the proposals set out in the original review. This included a commitment to formally review the operation of R174A and R247A following one year of use to evaluate whether there have been any adverse consequences for the market in medicines or for patient safety as a consequence of the operation of these regulations. This is the formal government report of that review.
2. Background
2.1 Regulation 174
R174 is the mechanism which allows for temporary authorisation of an unlicensed medicine, such as a vaccine, where such an authorisation is needed in response to certain public health threats, such as a pandemic. The amendments that were made following the consultation built on and supplemented the existing R174.
While it was implicit under R174 that a decision to authorise the supply of an unlicensed medicinal product could carry certain conditions, it was not expressly articulated. The proposals taken to consultation in August 2020 were to amend the Human Medicines Regulations to make it explicit that the supply of products, including COVID-19 vaccines, which are temporarily authorised under R174 may be subject to conditions. The imposition of conditions enables the licensing authority to define the safeguards that are a pre-requisite for the safe supply and use of the product and without which authorisation would not be valid.
The consultation responses on the proposed changes to R174 focused largely on concerns about the existing provision, rather than the changes consulted on. The government’s response to this was to include a requirement to review its operation after one year of use. However, as planned, the regulation was also amended to make it explicit that the supply of products which are temporarily authorised under R174, may be subject to conditions. The R174A provision, and the statutory framework setting out the action to be taken in the event of a breach of the conditions, enabled the licensing authority the Medicines and Healthcare products Regulatory Agency (MHRA) to define the safeguards for the safe supply and use of the unlicensed products.
2.2 Use of Regulation 174A
The R174A provision was first used when the MHRA temporarily authorised FluBlok on 22 October 2020. FluBlok was first deployed on 18 November 2020 as part of the United Kingdom’s 2020 to 2021 seasonal flu programme to meet a public health need, therefore we are legally required to conduct and publish the results of a review of R174A after 18 November 2021 (when a full year has passed since its first use).
In the 12 months following Flublok’s authorisation, R174A has been used for a number of COVID-19 vaccines and treatments. It was used in the temporary authorisation of the Pfizer COVID-19 vaccine on 2 December 2020 and the AstraZeneca COVID-19 vaccine on 30 December 2020. These vaccines were deployed on 8 December 2020 and 4 January 2021 respectively and have been used extensively in the COVID-19 vaccination programme under these authorisations.
The Moderna COVID-19 vaccine was also authorised under R174 (and subject to conditions under R174A) on 8 January 2021, however no Moderna supply was provided under R174A. Supply of the Moderna vaccine was not anticipated until early April 2021, by which time a Great Britain (GB) conditional marketing authorisation (CMA) for the Moderna vaccine was in place, issued by the MHRA on 31 March 2021. This CMA was put in place via the European Commission Decision Reliance Procedure, following an application from Moderna on 27 March 2021. All supply of Moderna in GB was deployed under the CMA, and Northern Ireland (NI) supply was under the European Medicines Agency (EMA) CMA, issued on 6 January 2021 (the issue of regulatory divergence between NI and GB is explained below).
More recently R174A has been used in the authorisation of 2 COVID-19 treatments in Northern Ireland:
- Ronapreve, a neutralising monoclonal antibody, authorised for use on 20 August 2021
- Molnupiravir, an antiviral, authorised on 4 November 2021
At the same time, these 2 treatments were authorised for use in Great Britain under CMAs, and the reasons for taking this dual approach concerns the arrangements agreed between the EU and UK regarding the Northern Ireland Protocol.
Since 1 January 2021, due to the Northern Ireland Protocol, while Great Britain is subject to the MHRA’s regulatory authority, Northern Ireland continues to be bound by the rules and decisions of the EMA. This means that medicines authorised by the EMA can be used in Northern Ireland, and that the conditions imposed by the EMA should be followed. At the time of MHRA authorisation, the EMA had not authorised either Ronapreve or Molnupiravir, therefore a temporary R174A approval was put in place to cover use of these treatments in Northern Ireland, pending a licensing decision by the EMA. Ronapreve received EMA authorisation on 11 November 2021 while Molnupiravir submitted an application for EMA authorisation on 23 November 2021 and is still awaiting approval.
In the case of both the Pfizer and AstraZeneca COVID-19 vaccines, the conditions that were imposed were designed to support quality and safety of the vaccines. The conditions covered:
- batch testing and manufacturer quality assurance
- deployment and handling guidance
- pharmacovigilance
In the case of Ronapreve and Molnupiravir, the conditions attached though R174A essentially relied on the corresponding MHRA GB CMAs, which specify that authorisation was contingent on supply meeting all the conditions and requirements set out within them. The conditions attached to the Flublok R174A used in the 2020 to 2021 annual flu vaccination were intended to support the quality and safety of the medicine, including batch testing and pharmacovigilance, and these ceased in May 2021 at the end of the flu season. The correspondence relating to this decision, which included the conditions of authorisation, is not publicly available to ensure we minimise the risk of prejudicing the commercial interests of the company responsible for the marketing of the product in the UK.
The key use in practice of R174A has been for the Pfizer and AstraZeneca COVID-19 vaccines. As previously mentioned, conditions were also agreed for the Moderna COVID-19 vaccine, however Moderna was never deployed under R174A.
2.3 Regulation 247A
R247A is the mechanism that allows the expansion of the workforce who are legally and safely able to administer a COVID-19 or influenza vaccine under an approved protocol, to ensure that the UK has the available workforce to administer vaccines at the pace required. The proposals taken to review in August 2021 were as follows:
- expanding the scope of patient group directions (PGDs) to allow the administration of any medicine, including COVID-19 vaccines, which have been temporarily authorised under R174A (so that PGDs could be used alongside the new protocols)
- introducing a new national protocol, to allow those who are registered healthcare professionals who do not normally vaccinate, and people who are not registered healthcare professionals, to safely administer a COVID-19 or influenza vaccine
- expanding the workforce legally allowed to administer vaccines under NHS and local authority occupational health schemes, so that additional healthcare professionals in the occupational health workforce can administer vaccines
Following feedback from respondents, further changes were made to the proposals to create an additional level of reassurance in relation to the expanded workforce by making it clear that the new national protocol should include, where appropriate, requirements for the supervision of an additional experienced vaccinator.
2.4 Use of Regulation 247A
Under R247A, the first national protocol for the COVID-19 vaccination programme was issued on 18 December 2020 for the Pfizer COVID-19 vaccine. Since then, national protocols have been approved by ministers and issued for the AstraZeneca COVID-19 vaccine, the Moderna COVID-19 vaccine, and the inactivated influenza vaccines used for the annual flu vaccination programme. This report meets the requirement to conduct and publish the results of a review of R247A after 18 December 2021 when a full year has passed since the Pfizer national protocol was first published.
In practice these protocols have become a key tool to support the programmes of mass vaccination against COVID-19 and influenza, in particular, where administration takes place at mass vaccination centres and the various roles (drawing up the vaccine, assessing individuals, administering the vaccine, overall clinical supervision) are split between a number of different people. Immunisations at some GP practices and community pharmacies under their ordinary annual flu vaccination arrangements (that is, not involving co-administration of COVID-19 vaccinations) have continued to be PGD based rather than protocol based. This is in part due to lower throughput at some sites and because the vaccines themselves are supplied by the manufacturers in single dose syringes and so a splitting of roles is not of practical value.
Full details of the national protocols issued to date can be found in the table at annex A (below).
3. Stakeholder review
To inform this report on the use of R174A and R247A, a stakeholder review was held between 29 November 2021 and 7 January 2022.
The review was conducted by email and sent to 28 organisations representing the UK’s medicines industry, pharmacy groups, medical groups and patient organisations. A full list of the organisations consulted, along with the email sent inviting them to participate, can be found at annex B.
Stakeholder views were sought on the following questions:
- Have there been any adverse consequences for the market in medicines as a consequence of the operation of regulation 174A?
- Have there been any adverse consequences for patient safety as a consequence of the operation of regulation 174A?
- Have there been any adverse consequences for the market in medicines as a consequence of the operation of regulation 247A?
- Have there been any adverse consequences for patient safety as a consequence of the operation of regulation 247A?
Ten responses were received in total. The responses were broadly positive, highlighting the flexibility that had been afforded by the regulations, which have been crucial in delivering the COVID-19 vaccination programme at pace. On the issue of market impacts, the legislative requirement to review the impact of R174A references adverse consequences for the market for medicines while R247A specifically references adverse consequences for the prescription-only medicines market. For both R174A and R247A DHSC asked about adverse consequences for the market for medicines generally, to ensure consistency between the questions and to gather broader views about the use of the regulations to inform future decision making.
3.1 Regulation 174A
None of the 10 respondents to the review were aware of any specific adverse consequences for the market in medicines as a direct consequence of the operation of R147A.
However, one respondent noted that, while their overwhelming view was that the use of R174A has been instrumental in the delivery of the COVID-19 vaccination programme, it should be acknowledged that the emergency mechanism may have potentially led to vaccine hesitancy among some communities and members of the public. They noted that risks of the public perceiving shortcuts being taken in the authorisation process, European and global inconsistencies with regards to time to authorisation, and the fact that new safety signals did emerge following authorisation and commencement of the UK vaccination programme may have damaged public confidence in the vaccines and caused fewer citizens to accept the offer of vaccination.
They also acknowledged this issue had been recognised and attempts had been made to mitigate these concerns at both regional and local levels. Clear explanations of the mechanism and supporting guidance had been useful to minimise the impact of this potential effect, and they suggested that it would be helpful to consider providing such information at an earlier point, should R174A be used again in any future vaccine deployment.
Nine out of 10 respondents were not aware of any adverse consequences for patient safety as a consequence of the operation of R147A.
One respondent noted that without the ability to mobilise vaccine supply through a temporary authorisation, the vaccination programme would not have moved at the rapid pace at which R174A had enabled it to. They added that the very low number of adverse events occurring as a result of COVID-19 vaccination compared with very high number of successful COVID-19 vaccinations suggested that R174A has had a positive impact during this pandemic.
Another respondent commented that the COVID-19 vaccines authorised under R174A had subsequently been linked to a very low number of adverse events, some of which had been serious, in particular the risks of myocarditis with both the Pfizer and Moderna COVID-19 vaccines and thrombosis with thrombocytopenia with the AstraZeneca COVD-19 vaccine. They noted that it was not clear whether these risks would have been identified had the vaccines been authorised under the usual arrangements of a CMA. They added that it was also not clear whether, if these risks had been identified, it would have influenced decisions by the MHRA in terms of licensing, given the public health emergency and subsequent authorisation of the vaccines under a CMA.
In light of these comments, it is important to note that each COVID-19 vaccine candidate was only authorised once it had met robust standards of effectiveness, safety and quality set by the medicines regulator, MHRA. The use of R174A did not alter this strict process and vaccines authorised via this route underwent the same rigorous quality checks as vaccines authorised under CMAs.
3.2 Regulation 247A
No respondents were aware of any adverse consequences for the market in medicines as a consequence of the operation of R247A.
One respondent commented that R247A had created the option of a different vaccine delivery model, which led to higher programme efficiency while allowing the continuation of business-as-usual activities, where appropriate. Another said that the introduction of R247A had demonstrated that relaxing elements of the regulatory framework surrounding community pharmacies had still resulted in safe and efficient delivery of services for patients. They added that they would welcome further discussions with government and system leaders to explore other changes that could be made to increase vaccination capacity.
No respondents were aware of any adverse consequences for patient safety as a consequence of the operation of R247A.
One respondent commented that the flexibility offered by R247A with regards to the vaccination workforce had been a key enabler in delivering the COVID-19 vaccination programme at pace. They added that the ability to maximise the workforce capacity by using non-registered staff and thereby targeting the limited numbers of registered healthcare professionals to key clinical roles had been instrumental to the success of the programme. While there had been concern about whether all individuals involved in the delivery of vaccines under an R247A national protocol would have the appropriate knowledge, skills and competence, this had been mitigated by the rigorous training and competency assessment programmes in place since the launch of the programme.
Another respondent commented on the importance of the non-clinical workforce, and the valuable role they can play (and have played) in delivering the COVID-19 vaccination programme as well as the need to ensure that there continues to be sufficiently accessible and appropriate training available to non-clinical staff.
A further respondent commented that there had been no adverse consequences that they were aware of and, conversely, that there had been a significant benefit to the overall vaccination programme by allowing large volumes of vaccines to be delivered through various models. The combination of PGDs and R247A national protocols has enabled innovation across the system, ultimately to the benefit of individuals. They also commented that under the current system, pharmacy technicians can operate under a R247A national protocol but not under a PGD. They suggested that as registered healthcare professionals, pharmacy technicians should be empowered to operate under a PGD and they added that the COVID-19 vaccination programme has demonstrated that pharmacy technicians can safely administer vaccinations for individuals, as well as being a key part in meeting capacity challenges of various vaccination programmes.
This view was echoed by another respondent, who commented that R247A had allowed for a range of individuals to be able to participate in a vaccination programme as vaccinators, whereas a PGD is more limited. They recommended that that registered pharmacy technicians should be able to supply a medicine under a PGD, or at least that they should be able to administer vaccinations under a PGD.
Finally, one respondent commented that while the scale and pace at which the COVID-19 vaccination programme had been delivered presented potential safety risks, they were not aware of any evidence that individuals had suffered significant harm as a result, or that any harms that had been suffered were disproportionate to health benefits. Additionally, they commented that they would not advocate the expansion of R247A beyond its current scope of being used to expand the workforce legally able to administer a COVID-19 or influenza vaccine during the pandemic.
Annex A: national protocols issued to date
1. Pfizer/BioNTech COVID-19 vaccine
See the national protocol for COVID-19 mRNA vaccine BNT162b2 (Pfizer/BioNTech).
| National protocols | Date issued |
|---|---|
| National protocol for COVID-19 mRNA vaccine BNT162b2 (Pfizer/BioNTech) v01.00 | 18 December 2020 |
| National protocol for COVID-19 mRNA vaccine BNT162b2 (Pfizer/BioNTech) v02.00 | 10 January 2021 |
| National protocol for COVID-19 mRNA vaccine BNT162b2 (Pfizer/BioNTech) v03.00 | 13 April 2021 |
| National protocol for COVID-19 mRNA vaccine BNT162b2 (Pfizer/BioNTech) v04.00 | 13 August 2021 |
| National protocol for COVID-19 mRNA vaccine BNT162b2 (Pfizer/BioNTech) v05.00 | 21 September 2021 |
| National protocol for COVID-19 mRNA vaccine BNT162b2 (Pfizer/BioNTech) v06.00 | 20 November 2021 |
| National protocol for Comirnaty® COVID-19 mRNA vaccine v01.00 | 13 August 2021 |
| National protocol for Comirnaty® COVID-19 mRNA vaccine v02.00 | 21 September 2021 |
| National protocol for Comirnaty® COVID-19 mRNA vaccine v03.00 | 20 November 2021 |
| National protocol for Comirnaty® COVID-19 mRNA vaccine v04.00 | 8 December 2021 |
| National protocol for Comirnaty® COVID-19 mRNA vaccine v05.00 | 16 December 2021 |
| National protocol for Comirnaty® 30microgram/dose COVID-19 mRNA vaccine v06.00 | 7 January 2022 |
| National protocol for Comirnaty® 10 microgram/dose COVID-19 mRNA vaccine v01.00 | 24 January 2022 |
2. AstraZeneca COVID-19 vaccine
See the national protocol for COVID-19 Vaccine AstraZeneca (ChAdOx1-S [recombinant]).
| National protocols | Date issued |
|---|---|
| National protocol for COVID-19 Vaccine AstraZeneca, (ChAdOx1-S [recombinant]) v01.00 | 10 January 2021 |
| National protocol for COVID-19 Vaccine AstraZeneca, (ChAdOx1-S [recombinant]) v02.00 | 14 April 2021 |
| National protocol for COVID-19 Vaccine AstraZeneca, (ChAdOx1-S [recombinant]) v03.00 | 27 April 2021 |
| National protocol for COVID-19 Vaccine AstraZeneca, (ChAdOx1-S [recombinant]) v04.00 | 29 October 2021 |
3. Moderna COVID-19 vaccine
See the national protocol for Spikevax (formerly COVID-19 Vaccine Moderna).
| National protocols | Date issued |
|---|---|
| National protocol for COVID-19 Vaccine Moderna v01.00 | 8 April 2021 |
| National protocol for Spikevax (formerly COVID-19 Vaccine Moderna) v02.00 | 8 October 2021 |
| National protocol for Spikevax (formerly COVID-19 Vaccine Moderna) v03.00 | 9 December 2021 |
| National protocol for Spikevax (formerly COVID-19 Vaccine Moderna) v04.00 | 16 December 2021 |
| National protocol for Spikevax (formerly COVID-19 Vaccine Moderna) v05.00 | 20 January 2022 |
4. Inactivated influenza vaccine
See the national protocol for inactivated influenza vaccine.
| National protocols | Date issued |
|---|---|
| National protocol for inactivated influenza vaccine v02.00 | 1 September 2021 |
| National protocol for inactivated influenza vaccine v03.00 | 5 November 2021 |
Annex B: organisations consulted
- Medicines and Healthcare products Regulatory Agency (MHRA)
- Joint Committee on Vaccination and Immunisation (JCVI)
- UK Health Security Agency (UKHSA)
- NHS England and NHS Improvement (NHSEI)
- Royal College of General Practitioners
- Royal College of Nursing
- The Patients Association
- UK Medicines Information
- The Association of the British Pharmaceutical Industry
- British Generic Manufacturers Association
- Ethical Medicines Industry Group
- General Pharmaceutical Council
- Royal Pharmaceutical Society
- Company Chemists Association
- Pharmaceutical Services Negotiating Committee
- National Pharmacy Association
- Specialist Pharmacy Services
- Royal College of Physicians
- British Medical Association
- Royal College of Paediatrics and Child Health
- General Medical Council
- Royal College of General Practitioners
- National Voices
- Vaccines Taskforce
- Deputy Chief Medical Officers (DCMOs) and Chief Medical Officers (CMOs)
- Welsh Government
- Scottish Government
- Northern Ireland Government
Text of invitation sent to stakeholders
Dear colleagues,
We are writing to invite you to participate in a targeted government review, conducted by the Department of Health and Social Care (DHSC) on behalf of the Secretary of State, as part of a formal review of the impact of the implementation of Regulation 174A of the Human Medicines Regulations 2012 (R174A) (HMRs) and Regulation 247A of the HMRs (R247A).
The Secretary of State for Health and Social Care of the United Kingdom is legally obliged to conduct these reviews following a year of their first use, in accordance with the conditions attached to the regulations. The conclusions drawn from this review on the operation of R174A and R247A will be set out in a report published on GOV.UK and copies will be placed in the libraries of both Houses of Parliament.
The review comprises of 4 questions which seek your views on the consequences for the market in medicines or for patient safety as a consequence of the operation of these regulations. The focus of these questions are in line with the requirements of the review as set out within the legislation for R174A and R247A.
As key stakeholders we are seeking your input to the review. In particular, we would be grateful for your responses to the following questions:
- Have there been any adverse consequences for the market in medicines as a consequence of the operation of Regulation 174A?
- Have there been any adverse consequences for patient safety as a consequence of the operation of Regulation 174A?
- Have there been any adverse consequences for the market in medicines as a consequence of the operation of Regulation 247A?
- Have there been any adverse consequences for patient safety as a consequence of the operation of Regulation 247A?
The attached document provides a background of the implementation of R174A and R247A to date, as well as a suggested framework for your answers, however these are only meant to serve as guidelines. We encourage all stakeholders to approach these questions as they deem best in order to ensure the government’s review of R174A and R247A produces as broad a range of responses as possible.
If you require the review questions in a particular format, please get in touch and we will accommodate this.
Please note that any responses to this review specifically referenced in the report will be listed by organisation – the names of individual respondents will not be published in the report.
We would be grateful if you could provide any responses, or nil responses, to us by close of play Monday 20 December 2021.
If you have any queries, please do not hesitate to get in touch by contacting the following email address: r174r247review@dhsc.gov.uk.
Kind regards,
COVID-19 Vaccines Deployment Team
DHSC