Due to the nature of pharmaceutical drugs and devices and their effect on the user, regulatory bodies are typically conservative in making changes to the regulatory process. The COVID-19 pandemic has required unprecedented levels of flexibility to enable potentially life-saving treatments to be assessed and developed quickly. The MHRA, along with the EMA and FDA shortly after, took very proactive steps to provide a framework for potential leads.
The MHRA and DHSC implemented a triage system during the initial few weeks of the pandemic to pre-evaluate potential products, suppliers, and leads. In conjunction with the Cabinet Office and the Department of Health and Social Care, the regulator was able to guide those they’d identified as potentially viable leads through formal assessments via structured online Q&As to enable their fast-tracking.
To expedite the approval of drugs and devices in response to COVID-19, the MHRA issued regularly updated guidance on flexibilities in relation to the normal process. This included accelerated reviews of clinical trials, as well as less onerous reporting and the use of adaptive clinic trials. Routine inspections were halted or replaced by desktop assessments, reduced testing was implemented for imported products to prevent stockpiling, and reviews of licenses to add additional QPs were prioritised.
The advice in relation to COVID-19 enquiries for medical devices, such as for PPE, test kits, and equipment, was hastened and the provision of exceptional use certifications for devices such as CPAP machines and ventilators meant that critical items were not delayed. MHRA also extended the suspension of the implementation of the new MDR (medical device regulations) for 12 months. The regulator also accelerated assessments of variations and license applications for medicines, as well as extending the implementation dates for other key regulatory changes to minimise the impact on manufacturers. There were also other changes and relaxation of some of the requirements around pharmacovigilance, GMP/GDP, hospital blood banks, licensing, and RFI responses.
Whilst these changes may seem minor and relatively insignificant in terms of their outward appearance, they are significant and ground-breaking in comparison to the conservative approach usually taken by the regulator. Under normal circumstances, regulatory changes can take up to five years to implement but were actioned within a matter of weeks in response to the crisis. As these changes are relaxations in the normal operating parameters, however, they have been easier to implement.
It is anticipated that the flexibilities introduced by MHRA will be rescinded as the situation around the control and mitigation of the effects of the pandemic becomes more normalised. Whilst there will be some in the industry that will seek extensions and implementation of some of these changes to be made permanent, all regulators (including MHRA) have been clear that these flexibilities are time-limited. Furthermore, the COVID-19 operating standards and procedures are not sustainable as MHRA has had to halt or slow the usual activities and the implementation of previously planned changes during this period. Pre-COVID operations will now need to be restarted to allow the agency to provide the level of support expected by the industry.
The temporary changes in regulations have had a significant impact on the development of treatments and products, with high profile examples including ventilators, PPE, and clinical development programmes to re-purpose existing molecules. These changes have had the largest impact on the development of a vaccine to treat coronavirus infections. MHRA’s involvement in drastically shortening the development time from 15 years or more to a just a few years has been critical.
The approval process for a vaccine will hinge on MHRA’s acceptance of the clinical data and safety profile. Whilst the risk to benefit ratio may not be ideal, there will be a lot of pressure from all sides to ensure any deficiencies are addressed pragmatically and quickly. The main areas for concern will be side effects and adverse reactions (known and unknown) and their potential severity. As the number of subjects in the trials is very small compared to the potential recipient population, any adverse effect will need to be carefully scrutinised as part of the approval process.
The development of medicines is traditionally a slow-moving sector and whilst change is possible, there has to be strong external forces for it to happen quickly. This is exactly what has happened during the COVID-19 outbreak, where regulators have encouraged the pharmaceutical and medical device industry to engage in a collaborative manner to enable accelerated developments. This is not sustainable after the pandemic has subsided as the traditional role of the regulator is to regulate and ensure the safety of public health. This level of collaborative flexibility will only occur again where there is a similar situation of unmet clinical need and urgency. Hopefully, this will be highly unlikely in our lifetimes.
The pandemic has also generated more public and government awareness of the importance of the life sciences sector. It is anticipated that this will lead to ensuring an improvement in adequate levels of funding so the UK can regain its place as a world leader in this industry. However, the COVID-19 outbreak has also highlighted the impact of Brexit, where fewer manufacturers will want to base their development and registration activities in the UK as opposed to the EU. What this might mean for the UK healthcare industry remains to be seen.