There are number of key steps, processes and stakeholders involved in the approval of and access to a medicine in the UK. This article summarises the process to help explain how this works.
Medicines and Healthcare products Regulatory Agency (MHRA)
The MHRA is an executive agency part of the Department of Health and Social Care (DHSC) in the UK. It is responsible for ensuring that medicines and medical devices work and are acceptably safe.
The MHRA has many roles and responsibilities including the assessment and authorisation of the sale and supply (Marketing Authorisation also known as MA) of medicines in the UK.
Other key MHRA responsibilities include: the regulation of clinical trials for medicines and medical devices; the reporting, investigating and monitoring of adverse events to medicines and incidents with medical devices through the Yellow Card Scheme; the monitoring, surveillance, regulation and investigation of many other health-related areas.
Clinical trials (also called clinical studies)
Before a medicine or a medical device is approved for use, it needs to undergo a rigorous and comprehensive clinical trial process which usually takes many years. However, as we have seen for medicines associated with COVID-19 (e.g. vaccines, monoclonal antibodies, etc.), some of these clinical trials were of shorter duration.
Clinical trials enable pharmaceutical and medical device companies to test their medicines or devices to ensure they work (efficacy) and that their side effects (also called adverse events) are at an acceptable level for patients. As part of this process, new medicines are also compared with either a ‘dummy’ treatment (also called placebo: a medicine given in the same way but without any therapeutic effect) or the reference treatment (‘standard’ or ‘gold standard’) in a specific therapy area.
If we focus on clinical trials for pharmaceutical products, following the ‘pre-clinical’ laboratory research stages, there are four key phases in a clinical study: phases 1, 2, 3 and 4. You can download a visual summarising the objectives, number of participants and duration of each phase here.
The data from all the various clinical trials are compiled in a large comprehensive file (dossier) which is submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) for their review, assessment and opinion. If the MHRA are satisfied with the safety and efficacy data of a new medicine, as well as compliance with the manufacturing quality standards, they will eventually issue a Marketing Authorisation.
Marketing authorisation (MA) and Temporary Authorisation (e.g. for COVID-19 vaccines)
The Regulatory Department of a pharmaceutical company is usually responsible for submitting the MA application dossier to the MHRA. Like the clinical trial process, it involves many international stakeholders and this can take several years, taking into account the time for the MHRA to review the dossier and raise questions to the applicant, for the pharmaceutical company to provide specific answers, etc.
Some MA applications may be fast-tracked ‘If there is compelling evidence of benefit in a public health emergency or if there is a shortage of supply of an essential medicine that has been verified by the Department of Health and Social Care (DHSC)‘ 1.
It is worth noting that the COVID-19 vaccines did not receive a ‘marketing authorisation’, as such. Instead, these medicines received a ‘temporary Authorisation under Regulation 174′ 2,3 which ‘permits the supply to and by the Crown’ 3 of the various brands of COVID-19 vaccines. This authorisation was granted ‘based on the safety, quality and efficacy data submitted‘ 2,3 by the various vaccine manufacturers covering a specific period of time.
Early access to medicines scheme (EAMS)
When there is a clear unmet medical need, the EAMS enables patients with conditions that are life-threatening or seriously impact their lives to gain access to medicines that do not yet have an MA.
In this case the MHRA ‘will give a scientific opinion on the benefit/risk balance of the medicine, based on the data available when the EAMS submission was made. The opinion lasts for a year and can be renewed’4.
It is worth noting that the EAMS is a voluntary scheme and these process and outcome do not replace the standard approval procedures for medicines.
New medicine cost-effectiveness appraisals
In the UK, once a medicine has been approved, it is usually evaluated for the balance between the benefit it brings to patients and its cost.
This cost-effectiveness process can also take a significant amount of time and takes place through the following organisations according to the nation:
England: National Institute for Health and Care Excellence (NICE) – https://www.nice.org.uk/about/what-we-do
Wales: NICE/All Wales Medicines Strategy Group (AWMSG) – https://awttc.nhs.wales/about-us1/our-committees/#AWMSG
Scotland: Scottish Medicines Consortium (SMC) https://www.scottishmedicines.org.uk/about-us/
Northern Ireland: Department of Health (DoH) – https://www.health-ni.gov.uk/
USA: The Emergency Use Authorisation (EUA) process
In the USA, the Federal Drug Administration (FDA) may resort to EUAs which are administered by the Emergency Use Authorization (EUA) Authority. An EUA allows the FDA to help strengthen the nation’s public health protections against a number of threats including infectious diseases, such as COVID-19.
When an emergency use authorization is declared appropriate, ‘the FDA may authorize unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN [chemical, biological, radiological, and nuclear] threat agents when certain criteria are met, including [when] there are no adequate, approved, and available alternatives.’5
In the context of COVID-19, EUAs have been used not only for the vaccines and antiviral treatments such as remdesivir, approved for the treatment of patients requiring hospitalisation, but also for a wide range of medical devices associated with the management of the disease. These include, for instance, blood purification devices, ventilators, in vitro diagnostics, infusion pumps, personal protective equipment (PPE), etc.
The approval of a new medicine and the steps that follow to ensure it is successfully rolled out to patients are complex and lengthy. Fortunately, in the case of public health emergencies, such as the Covid-19 pandemic, health authorities are able to accelerate some of their processes to facilitate quicker access to new treatments for patients.
1. Apply for a licence to market a medicine in the UK. Website last accessed 17.9.2021.
2. Conditions of Authorisation for COVID-19 Vaccine Pfizer/BioNTech (Regulation 174). Website last accessed 17.9.2021
3. Conditions for authorisation for emergency supply under Regulation 174 for COVID-19 Vaccine AstraZeneca. Website last accessed 17.9.2021
4. Apply for the early access to medicines scheme (EAMS). Website last accessed 17.9.2021.
5. Emergency Use Authorization. Website last accessed 17.9.2021
This article was written by Valerie Brisse-Uhlig, a volunteer for Immunodeficiency UK, and was approved by the Chair of the Immunodeficiency UK Medical Panel.
Posted October 2021