The regulatory challenges of COVID-19 for life sciences
Marie Manley, partner at law firm Sidley Austin looks at how UK and EU life sciences are responding to the regulatory requirements presented by COVID-19.
COVID-19 presents an unprecedented challenge to the global life sciences industry. The UK and EU regulators have worked to provide up-to-date guidance in response to the evolving crisis, as well as to support research and development (R&D) that they hope will contain the impact of the spread. The regulators must continue to coordinate in order to maximise clarity in this uncertain environment in which the far-reaching consequences of the pandemic are only just starting to manifest.
This article provides guidance as to the response of UK and EU regulators so far 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). We also summarise key R&D initiatives at a UK and EU level.
1. Medicinal Products
Clinical trials
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 (i) submitting paperwork for trials that have been halted; (ii) restarting a trial after it has been halted; (iii) providing the investigational medicinal product (IMP) to trial participants; (iv) remote monitoring for trials, including replacing in-person visits with phone calls and reducing the number of participant monitoring visits; (v) reporting of serious adverse events (SAEs) and submission of annual safety reports (DSURs) and end-of-trial notifications; (vi) protocol deviations, serious breaches and waivers; and (vii) signatures.
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. The EMA has published a statement calling 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, concerned that compassionate use programs may not generate the required conclusive data.
In addition to its guidance outlined above, the EMA has issued a draft document entitled “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 April 25.
It is unavoidable that scheduled clinical trials will be delayed. Already large pharmaceutical companies have announced delays to their clinical trials and have revised their R&D plans in light of COVID-19. They have halted enrolment in most ongoing clinical trials and have also postponed studies. It is likely that many other companies will follow suit in the forthcoming weeks and months.
MHRA inspections
The MHRA has announced that it will conduct only essential Good Practice inspections of laboratories, clinical trials, manufacturing, distribution and pharmacovigilance until further notice. The MHRA 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 the active pharmaceutical ingredients imported from China and extensive travel restrictions, there have been concerns that the COVID-19 outbreak may disrupt pharmaceutical supply chains into the EU.
The EMA, European Commission (Commission) and national competent authorities have organised the EU Executive Steering Group on shortages of medicines caused by major events. The EMA has already taken other measures to minimise shortages such as coordinating 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 working closely with the Coordination Groups for Mutual Recognition and Decentralised Procedures, which will coordinate 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 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.
2. Medical Devices
COVID-19 medical devices – fast-track approval
The Commission 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 (even though the conformity assessment procedures, including the affixing of CE marking, have not been fully finalised according to the harmonised rules) 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.
On March 25, the MHRA announced that it may authorise the supply of non-CE-marked devices “in the interest of the protection of health.” The 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 (e.g., 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.
The MHRA has also created a specific form for manufacturers to submit COVID-19 test kits for regulatory approval. The agency is developing specifications for COVID-19 tests and will make these available as soon as possible.
Delayed implementation of MDR/IVDR
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 because of the reassessment of the notified bodies coupled with necessary changes due to Brexit. It is therefore unsurprising that the Commission is working on a proposal to postpone the implementation of the MDR by one year. The Commission 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.
3. COVID-19 Research
The MHRA has stated that it is ready to prioritise and provide any assistance for clinical trials applications submitted for COVID-19. It has procedures for rapid scientific advice, reviews and approvals, as well as dedicated resources to ensuring that it can provide the necessary support. 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 announced 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 repurposing existing treatments to treat the virus, developing antibodies to help to target the virus and examining how people at greatest risk of catching the virus could be identified.
At a European level, the EMA has also stated that 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. The EMA provides a full waiver and a fast-track procedure for scientific advice.
The first global regulatory workshop on Covid-19, co-chaired by the EMA and the U.S. Food and Drug Administration, 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 and the Commission to discuss the development of vaccines against COVID-19.
The Commission has selected 17 COVID-19 research projects to receive €47.5 million in funding through Horizon 2020 on the condition that they share data rapidly. Two of the 17 projects selected are developing vaccines, led by researchers at the Karolinska Institutet in Sweden and AdaptVac, a Danish biotech startup.
In addition, the Innovative Medicines Initiative (IMI) has also announced a call for research proposals (with a deadline of March 31, 2020) 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 Commission through Horizon 2020.
The Commission has also announced the creation of Exscalate4CoV, its second-largest consortium. The consortium is led by the Italian pharmaceutical company Dompé farmaceutici SpA and is working to resolve the 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.