This week, we look at significant new guidance and initiatives in the EU and UK – and groundbreaking proposals for international regulatory collaboration in the development of COVID-19 treatments.
Medicines – international collaboration and clinical trials
The European Medicines Agency ("EMA") has endorsed a joint COVID-19 statement published by the International Coalition of Medicines Regulatory Authorities ("ICMRA"). The collaboration between regulators around the world is seen as a crucial step in facilitating rapid development, approval and global roll-out of safe and effective medicines for use against COVID-19.
The ICMRA is calling for:
- a global approach to achieve equitable access to COVID-19 therapies;
- regulators to increase the efficiency of their approval processes and decision-making in relation to Covid-19 therapies;
- governments and researchers to prioritise large, well-designed, controlled clinical trials which the ICMRA sees as most likely to generate the robust evidence for COVID-19 therapies needed for decision-making by regulators;
- the pharmaceutical industry to cooperate on therapeutics development and jointly address drug supply issues, shortages and decreased manufacturing capacities.
Separately, the European Commission has issued updated guidance on mitigating the disruption of clinical research into COVID-19 during the pandemic, with a view to ensuring that patients can continue to participate in the more than 200 coronavirus clinical trials now registered in the EU. The Commission's recommendations include:
- measures for distributing medicines safely to patients in clinical trials, taking into account social distancing requirements and potential limitations in trial site and hospital resources;
- remote source data verification to facilitate the marketing authorisation of coronavirus medicines (because of limitations verifying raw data in hospitals);
- the approach to urgent safety measures that might become necessary to protect trial participants or data robustness due to COVID-19 disruptions (e.g. temporary halts due to shortages, direct home distribution, transfer of participants to other sites etc).
Medical Devices – MDCG Guidance on ventilators and audits
The Medical Device Coordination Group ("MDCG") has issued two new COVID-19 guidance documents. The MDCG is composed of experts from all EU Member States, and chaired by a representative of the European Commission.
This week the MDCG provided guidance on the regulatory requirements for ventilators and related accessories in the EU. The guidance is targeted at industries that have expressed a willingness to help, but may not have experience in the sector. It outlines the different regulatory options available for supporting the production or placing on the market of ventilators, and gives a view on the feasibility of different approaches, in light of the need for rapid supply of these devices.
Earlier this month, the MDCG also published guidance of interest to existing stakeholders on temporary extraordinary measures for notified body audits during the COVID-19 crisis. These measures include:
- postponing on-site surveillance audits;
- replacing on-site audits with the remote audits;
- taking into account existing recent audit results where available;
- considering published international guidance on how to use technology and alternative auditing methods.
The MDCG makes it clear that the extraordinary measures should only be applied on a case-by-case basis and after appropriate risk assessment procedures have been undertaken.
On 26 April, the EU Commission's adjustment to its export authorisation scheme for PPE, first issued on 15 March, entered into force. The adjustment is a response to further surges in demand for PPE in light of the COVID-19 crisis.
The adjusted scheme, which is to remain in force for 30 days, includes:
- reducing the list of products that require export authorisation to protective spectacles and visors, masks and protective garments;
- requiring Member States to swiftly grant authorisations for exports for humanitarian purposes;
- extending the geographical exception to export authorisations for EFTA countries (Iceland, Liechtenstein, Norway and Switzerland), the Western Balkans (Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia and Serbia) and certain overseas countries and territories (such as the Faeroe Islands, Andorra and Gibraltar).
Medicines – GMP flexibilities and related guidance
The UK Medicines and Healthcare products Regulatory Agency ("MHRA") has published a list of temporary good manufacturing practice ("GMP") flexibilities for medicines manufacturers. The GMP flexibilities are designed to address specific challenges created by current international travel restrictions, and release quality system capacity to focus on ensuring a continuing supply of medicines required for the treatment of COVID-19. The flexibilities provide a relaxation, where appropriate, of the requirements for manufacture and importation of medicines, incident management and supplier audits.
To complement these new GMP flexibilities, the MHRA has also expanded its guidance to include the following:
- Creation of a dedicated email address for manufacturers to notify the MHRA when taking advantage of the current permitted flexibilities (GMDP@mhra.gov.uk). Guidance has also been given on the information that should be included in any notification to the MHRA.
- Confirmation that the MHRA expects manufacturers to notify it of any use of flexibilities on a 'do and tell' basis, meaning manufacturers do not need to notify the MHRA of their changes in advance.
For manufacturers affected by supply chain issues arising out of the current international travel restrictions, these flexibilities will be welcomed as they seek to continue to supply vital medicines. Similarly, the confirmation that there is no need to notify the MHRA prior to reliance on these GMP flexibilities will greatly assist businesses, as it allows for greater freedom to increase production at a time when regulators such as the MHRA are facing a huge amount of work and may be slower processing requests. However, businesses must note that even though proactive notification is not required the MHRA will require a justification for the use of the flexibility so it is essential that any changes to activities fall squarely within what is permitted, and that the Qualified Person is appropriately involved in any decision to implement the GMP flexibilities. Companies should ensure good records are kept to satisfy any post-market requests of this nature by the MHRA.
Remote Working Risk Reduction Guidance
Many bodies, including the UK's MHRA, the Office for Product Safety and Standards (OPSS) and the Health and Safety Executive (HSE), have issued guidance for various industries as an increasing number of businesses move towards working remotely. It is clear that regulators are recognising that, outside official product compliance issues, manufacturers and suppliers require guidance on how best to adapt to this new style of working and the challenges, as well as opportunities, it brings. The publication of this guidance suggests a broadening of the scope of support provided by regulators to companies, in recognition of the diverse challenges faced in this unique context.
Recognising the number of guidance documents being produced in that regard, the UK government has collated its COVID-19 related guidance on regulatory flexibilities designed to address the challenges that businesses are currently facing, into a single list available here. This list will continue to be updated and we will, of course, be writing about any significant changes for businesses.
Most recently, the MHRA guidance for organisations involved in the pharmaceutical lifecycle sets out various principles for maintaining control and managing risks. The MHRA is clear that electronic signatures can be used, but companies must be mindful of the associated risks, including how the approval signature on documents such as risk assessments can be attributed to an individual.
Regulators in the EU and UK continue to issue key guidance in the life sciences sector in response to the COVID-19 crisis. Whilst some of this guidance remains targeted at immediate shortages in essential medical devices and PPE, there is an increasing focus on the future – and, in particular, ensuring that the right steps are taken to facilitate the rapid development, approval and roll-out of safe and effective medicines for use against COVID-19. With this in mind, European bodies are looking to collaborate internationally to ensure that the approach taken is a global one, designed to achieve efficient development and equitable access to the COVID-19 therapies under trial.
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