COVID-19: regulatory implications for the UK and European life sciences industry
Marie Manley and co-authors from Sidley Austin explain the updates to regulations in the EU and UK in light of the COVID-19 coronavirus pandemic.
COVID-19 presents an unprecedented challenge to the global life sciences industry. UK and EU regulators have worked to provide up-to-date guidance in response to the evolving crisis and supported R&D in the hope that we will eventually be able to contain the impact of the spread. However, to maximise clarity in this uncertain environment, regulators must continue to co-ordinate and communicate their efforts.
This update provides guidance on the responses of UK and EU regulators in the areas of clinical trials, inspections and the continuity of supply in medicinal products and medical devices, as well as the proposed postponement of implementation of the medical device regulation (MDR) and in vitro diagnostics regulation (IVDR).
Both the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) have issued guidance on how investigators and sponsors should manage clinical trials during the outbreak.
The MHRA has stated that the first priority should be the safety of trial participants and this will remain its focus. Its guidance also covers:
- submitting paperwork for trials that have been halted
- restarting a trial after it has been halted
- providing the investigational medicinal product (IMP) to trial participants
- remote monitoring for trials, including replacing in-person visits with phone calls and reducing the number of participant monitoring visits
- reporting of serious adverse events (SAEs) and submission of annual safety reports (DSURs) and end-of-trial notifications
- protocol deviations, serious breaches and waivers
The EMA has published an EU-level harmonised set of recommendations, which are broadly similar to the advice of the MHRA. The guidance provides concrete information on changes and protocol deviations, which may be needed in the conduct of clinical trials to deal with extraordinary situations — for example, if trial participants need to be in self-isolation or quarantine, access to public places (including hospitals) is limited due to the risk of spreading infections and healthcare professionals are being reallocated. A statement published by the EMA urges the EU research community to prioritise large randomised controlled studies to generate conclusive evidence, proposing a harmonised approach to data collection and a robust methodology for COVID-19 clinical trials across the EU.
…regulators must continue to co-ordinate and communicate their efforts”
In addition to its guidance outlined above, the EMA has issued a draft document, titled Points to consider on implications of COVID-19 on methodological aspects of ongoing clinical trials, which is open to stakeholders for a four-week public consultation until 25 April.
It is unavoidable that scheduled clinical trials will be delayed. Large pharmaceutical companies have already announced delays to their clinical trials and revised their R&D plans in light of COVID-19. They have halted enrolment in most ongoing clinical trials and postponed certain studies. It is likely that many other companies will follow suit in the forthcoming weeks and months.
The MHRA has announced that it will conduct only essential Good Practice inspections of laboratories, clinical trials, manufacturing, distribution and pharmacovigilance until further notice. Instead, the regulatory body will prioritise essential on-site inspections linked to the UK government’s COVID-19 response or any other potential serious public health risk where the sites cannot be assessed remotely. Other MHRA inspections will be deferred to a later date.
Continuity of supply
With the majority of active pharmaceutical ingredients (APIs) imported from China and the extensive travel restrictions currently in place, there have been concerns that the COVID-19 outbreak may disrupt pharmaceutical supply chains into the EU.
The EMA, European Commission (EC) and national competent authorities have organised the EU Executive Steering Group on shortages of medicines caused by major events. Other measures the EMA has taken to minimise shortages include co-ordinating with national medicines regulators, EU pharmaceutical industry associations and marketing authorisation holders to spread awareness and information in respect of supply issues. The EMA is also working closely with the Co-ordination Groups for Mutual Recognition and Decentralised Procedures, which will organise actions for nationally authorised medicines.
In the UK, the National Health Service (NHS) measures to manage the supply shortage include the NHS Urgent Medicine Supply Advanced Service, allowing patients whose GP practice is closed to continue receiving their medicines and the Medicines Delivery Service, which supports vulnerable, self-isolating patients.
In addition, the UK government has written to suppliers informing them that the National Supply Disruption Response is monitoring the supply situation and providing resolution where possible.
COVID-19 medical devices – fast-track approval
The EC has published Recommendation (EU) 2020/403, which states that to address the shortage of personal protective equipment (PPE) necessary in the context of the COVID-19 outbreak, market surveillance authorities may authorise the provision of these products on the EU market for a limited period of time and while the necessary procedures are being carried out. This is even though the conformity assessment procedures, including the affixing of CE marking, have not been fully finalised according to the harmonised rules.
On 25 March, the MHRA announced that it may authorise the supply of non-CE-marked devices “in the interest of the protection of health.” The UK Department of Health and Social Care (DHSC) can grant its approval so that manufacturers are able to submit their applications for exemption from the regulations to the MHRA. The DHSC may grant its approval regarding ventilators as long as they comply with the necessary specifications. For any other relevant devices such as PPE (eg, surgical face masks and examination or surgical gloves), the application can be sent directly to the MHRA. Performance data and other relevant study data is expected to be provided as evidence that the device performs as intended.
The MHRA has issued specifications for the Rapidly Manufactured Ventilator System to be used in UK hospitals during the COVID-19 outbreak. The guidance outlines the clinical requirements based on the consensus of what is “minimally acceptable” performance in the opinion of the anaesthesia and intensive care medicine professionals and medical device regulators.
A specific form for manufacturers to submit COVID-19 test kits for regulatory approval has also been created by the MHRA. The agency is developing specifications for COVID-19 tests and will make these available as soon as possible.
Delayed implementation of MDR/IVDR
…there have been concerns that the COVID-19 outbreak may disrupt pharmaceutical supply chains into the EU”
MedTech Europe and the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE) have formally requested a pause in the implementation of the new MDR and IVDR, arguing that timely compliance is impossible due to the ongoing pandemic. The Association of British HealthTech Industries (ABHI) has announced that it fully supports this decision and has asked UK ministers and officials to make appropriate representations.
The industry was already struggling to meet the deadline for implementing the MDR on time – in particular due to the reassessment of the Notified Bodies, coupled with necessary changes because of Brexit. It is therefore unsurprising that the EC is working on a proposal to postpone the implementation of the MDR by one year. The EC aims to submit the proposal in early April, calling for the European Parliament and Council to adopt it quickly. This measure, although arguably precipitated by the COVID-19 disruptions, was eagerly anticipated by the industry, as well as national authorities and Notified Bodies, which have been vocal about the challenges in their preparedness.
The MHRA has stated that it is ready to prioritise and provide any assistance for clinical trial applications submitted for COVID-19. It has procedures for rapid scientific advice, reviews and approvals, as well as dedicated resources to ensure the necessary support is provided. The Health Research Authority has also announced an expedited review process in relation to Research Ethics Committee and NHS arrangements.
The UK Business Secretary has revealed that six COVID-19 research projects, including two focused on vaccination trials, will be the first to benefit from a share of £20 million in government investment. Other COVID-19 research projects receiving funding include some focusing on repurposing existing treatments to treat the virus, developing antibodies to help target the virus and examining how people at greatest risk of catching the virus could be identified.
In Europe, the EMA has also stated that review priority will be given to any new clinical trial applications for the treatment or prevention of a COVID-19 infection. Developers of medicines or vaccines are invited to contact the EMA as soon as possible with information about their proposed developments. A full waiver and a fast-track procedure for scientific advice will be provided by the EMA.
The first global regulatory workshop on COVID-19, co-chaired by the EMA and US Food and Drug Administration (FDA), was convened under the umbrella of the International Coalition of Medicines Regulatory Authorities. The meeting brought together delegates representing more than 20 medicine regulatory authorities globally, as well as experts from the World Health Organization (WHO) and the EC to discuss the development of vaccines against COVID-19.
The EC has selected 17 COVID-19 research projects to receive €47.5 million in funding through Horizon 2020 on the condition that they rapidly share their data. Two of the 17 projects selected are developing vaccines, led by researchers at the Karolinska Institutet in Sweden and AdaptVac, a Danish biotech start-up.
In addition, the Innovative Medicines Initiative (IMI) also announced a call for research proposals aiming to support projects that develop treatments and diagnostics to better tackle the COVID-19 outbreak and to increase preparedness for future possible outbreaks. The combined funding for this project could total €90 million. The IMI is a public-private partnership between the EU and the pharmaceutical industry association European Federation of Pharmaceutical Industries and Associations (EFPIA) and is funded by the EC through Horizon 2020.
The creation of Exscalate4CoV, has been announced by the EC, which is its second-largest consortium. Exscalate4CoV is led by the Italian pharmaceutical company Dompé farmaceutici SpA and is working to resolve the three-dimensional (3D) structures of essential COVID-19 proteins. This data will be used to generate computer models of likely future mutations of the virus and as the basis for in silico screening of compound libraries.
About the author
Marie Manley leads Sidley’s Life Sciences team in London and is a thought leader and adviser on EU and UK regulatory law. Prior to joining Sidley in 2018, Marie was a partner and head of the regulatory department at a major UK law firm. She has previously worked in Switzerland, New York and Brussels.
Co-authors: Zina Chatzidimitriadou, Will Holmes, Bethany Wise, Associates at Sidley Austin.
Clinical Development, Clinical Trials, Drug Manufacturing, Funding, Good Manufacturing Practice (GMP), investment, Legal, Manufacturing, Regulation & Legislation, Research & Development (R&D), Viruses
AdaptVac, Association of British HealthTech Industries (ABHI), Dompé farmaceutici SpA, European Commission (EC), European Confederation of Pharmaceutical Entrepreneurs (EUCOPE), European Federation of Pharmaceutical Industries and Associations (EFPIA), European Medicines Agency (EMA), Exscalate4CoV, Innovative Medicines Initiative (IMI), International Coalition of Medicines Regulatory Authorities, Karolinska Institutet, MedTech Europe, UK Department of Health and Social Care (DHSC), UK Medicines and Healthcare products Regulatory Agency (MHRA), UK National Health Service (NHS), US Food and Drug Administration (FDA), World Health Organization (WHO)