These extraordinary and unprecedented circumstances demand a rapid response from life sciences regulators who are continuously working to provide up-to-date guidance. New material is published on a daily basis and the regulatory response to the outbreak will continue to evolve following publication of this article. The aim of the authorities is mainly twofold: (i) to ensure that potential life-saving treatments and medical devices (e.g., ventilators) reach the market as fast as possible whilst protecting public health; and (ii) to protect healthcare professionals by ensuring that they have the appropriate personal protective equipment available.
I. Medicinal products
a) Clinical trials
The European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) have issued guidance on how investigators and sponsors should manage clinical trials during the outbreak.
The EMA guidance seeks to include most of the current guidance across Member States, and is broadly similar to the advice of the MHRA. In addition to its initial guidance, the EMA has released a draft document entitled ‘Points to consider on implications of Coronavirus disease (COVID-19) on methodological aspects of ongoing clinical trials’, which is open to stakeholders for public consultation until 25 April 2020.
The MHRA has recently added to and updated its existing guidance. The authority has stated that it will be as flexible and pragmatic as possible with regard to regulatory requirements for clinical trials during this time, recognising that clinical trial resources may be absent or redeployed from research activities and regulatory affairs towards frontline care. The first priority should be the safety of trial participants.
b) MHRA regulatory flexibilities
The MHRA has published industry guidance on various flexible approaches to regulation it is taking during the outbreak, including for inspections and good practice (GxP), medical devices, medicines regulation and pharmacovigilance. In respect of inspections and GxP, the MHRA has announced, among other measures, a risk-based prioritisation of GxP inspections and guidance on approval of GxP documents when working from home as well as flexibilities in regard to Good Distribution Practice (GDP), Good Manufacturing Practice (GMP) for medicines imported from third countries and Good Laboratory Practice (GLP).
c) Continuity of supply
The European Commission (EC) has issued guidelines on the optimal and rational supply of medicines to avoid shortages during the COVID-19 outbreak. The EC has also organised the EU Executive Steering Group on shortages of medicines caused by major events. The group has launched its industry single point of contact (i-SPOC) system whereby pharmaceutical companies report directly to the EMA in respect of shortages of critical medicines used to treat COVID-19. Medicines which are deemed crucial for the treatment of COVID-19, particularly in intensive care units, will be closely monitored for any possible disruption in the supply chain using the i-SPOC system.
The European medicines regulatory network has published and since updated a question-and-answer document to provide guidance on adaptations to the regulatory framework to address challenges arising from the pandemic, facilitating movement within the EU of crucial medicines for use in COVID-19 patients. The measures introduce a more flexible approach to marketing authorisations and regulatory procedures, manufacturing and importation of active pharmaceutical ingredients (APIs) and finished products, quality variations, and labelling and packaging requirements.
Further, the EC has published a Temporary Framework Communication to provide antitrust guidance to companies willing to temporarily cooperate and coordinate their activities in order to increase production in the most effective way and optimise supply of, in particular, urgently needed hospital medicines. The EC has also issued a “comfort letter” to Medicines for Europe concerning a specific cooperation project aimed at avoiding shortages of critical hospital medicines.
In the UK, the Government has stood up the National Supply Disruption Response (NSDR). The Government has also banned the parallel export of 196 medicines used to treat patients in intensive care units in order to protect crucial medicines for COVID-19 patients.
II. Medical devices and PPE
a) Continuity of supply
1.Fast-track approvals
The EC has published Recommendation (EU) 2020/403, which states that authorities may allow the provision of personal protective equipment (PPE) products on the EU market before conformity assessment procedures, including the affixing of CE marking, have been fully finalised for a limited period of time and while the necessary procedures are being carried out.
The MHRA has announced that it may authorise the supply of non-CE marked devices “in the interest of the protection of health”. Exceptional use applications are being processed to ensure a continued supply of non-CE marked devices where there is a significant clinical need and where there are no CE marked devices available. In addition, the MHRA has published guidance on the regulatory status of the products most urgently needed to prevent COVID-19 infections.
2.Production
The EC has made available guidance to assist manufacturers in ramping up production of essential medical equipment in PPE, leave-on hand cleaners and disinfectants, and 3D printing. The relevant European harmonised standards for PPE have been made freely available and the EC has adopted decisions on revised harmonised standards that will allow manufacturers to place high-performing devices on the market.
Further, the EC has coordinated a Joint Procurement Agreement for medical and protective equipment and has published guidance on how to use the flexibilities offered by the EU public procurement framework during the outbreak.
The British Standards Institution (BSI), the national standards body of the UK, has made a number of standards freely available including those for ventilators, hygiene (including hand washes) and PPE.
The MHRA has issued specifications for the Rapidly Manufactured Ventilator System (RMVS) and the Rapidly Manufactured Continuous Positive Airway Pressure (RMCAP) device to be used in UK hospitals during the outbreak, as well as initial specifications for tests and testing kits for COVID-19. In addition, the UK Government has published specifications setting out the regulatory and technical standards applicable to PPE that is most needed to prevent COVID-19 infections. The Government has also introduced a plan which incorporates general guidance and information on distribution and future supply of critical PPE to frontline workers.
3.Import/export
Economic operators in the EU require authorisation in order to export PPE used by medical workers treating COVID-19 patients, including masks and gowns. This measure expires on 25 April 2020 but is due to be extended by another 30 days. However, the restriction will be limited to face masks and will no longer apply to the Western Balkans and Gibraltar.
The UK Government is easing administrative requirements and barriers to imports of PPE as well as waiving import VAT and customs duty on vital medical from outside the EU. Border Force has introduced a new process for prioritising checks on medical equipment.
b) Delayed implementation of MDR
The European Parliament and European Council have adopted the EC’s proposal to postpone by one year the date of application of the Medical Devices Regulation (MDR) in order to allow stakeholders to prioritise the fight against the pandemic.
III. COVID-19 research
The EMA has stated that priority will be given to any new clinical trial applications for the treatment or prevention of COVID-19 infection as well as a full waiver and a fast-track procedure for scientific advice. It has formed the EMA pandemic Task Force (COVID-ETF) which assists with development, authorisation and safety monitoring of therapeutics and vaccines intended for treatment or prevention of COVID-19.
Four regulatory workshops on COVID-19, co-chaired by the EMA, have been convened under the umbrella of the International Coalition of Medicines Regulatory Authorities (ICMRA), bringing together delegates from over 28 medicines regulatory authorities globally, as well as experts from the World Health Organization (WHO) and the EC. In the most recent meeting on 16 April 2020, regulators agreed that regulatory rules should be applied with greater flexibility during the pandemic to facilitate development of potential COVID-19 treatments and secure continued supply of medicines.
In the UK, the MHRA is providing expedited scientific advice and rapid reviews of COVID-19 clinical trials applications. The Health Research Authority (HRA) has also announced an expedited review process in relation to Research Ethics Committee (REC) and NHS arrangements.
IV. Guidance on collection and transfusion of COVID-19 plasma
The EC has published a guidance document on the collection and transfusion of convalescent COVID-19 plasma which aims to facilitate a common approach to the donation, collection, testing, processing, storage, distribution and monitoring of convalescent plasma for the treatment of COVID-19 patients. The EC states that plasma transfusion is a potentially promising therapy for patients that can be made widely available at relatively short notice by blood services across the EU, and clinical trials have commenced in the UK and the US.
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