This blog post is based on a conversation between Ian Rees, Unit Manager Inspectorate Strategy and Innovation at the MHRA and the #CoffeeBuddies, a virtual discussion group hosted by Graham Combe and chaired by Professor Tony Sedgwick. Book to join #CoffeeBuddies on Tuesdays and Thursdays at 2.30 pm BST (GMT+1 hr) at Eventbrite.
The core principle of the Medicines & Healthcare products Regulatory Agency (MHRA) is to ensure that medicines, medical devices and blood components for transfusion are safe, of an appropriate quality, effective, and can be manufactured consistently.
The MHRA is made up of three centres:
The MHRA needs to do what is appropriate with each individual project, and to achieve this, works in collaboration with a range of organisations along the development pathway to create as integrated a programme as possible:
From an international perspective, the MHRA also works with:
The MHRA provides advice at any stage of development across the whole of the drug development lifecycle, and according to Rees, the earlier the developers request the advice, the better. The MHRA innovation office works with companies, research institutions, consortia and hospitals as they make the step from the bench to the bedside (the discovery and preclinical steps in translational medicine). This support includes innovations in drug and device development and in manufacturing processes. The innovation office also carries out horizon-scanning activities, keeping the MHRA as a whole up-to-date on emerging technologies, medicines and devices. The inspection and assessments office then covers the stages from preclinical to market.
One of the important roles of the innovation office is to provide confidential and informal expert regulatory information, advice and guidance, allowing inventors to begin to access the inspection pathway and engagement process. This free advice leads into the more formal scientific advice meetings and interim inspections. The MHRA also works with NICE to provide joint scientific advice to create clinical trials that could support and even accelerate adoption.
Companies and institutions developing innovative medicines for life threatening or seriously debilitating conditions with clear unmet medical need may also be able to access the early access to medicines scheme (EAMS). This allows patients to access drugs before marketing authorisation.
The innovation office was launched in 2013, and since then has dealt with more than a thousand enquiries and facilitated over 150 meetings. However, these have mostly been with research institutions and small and medium enterprises (SMEs); big pharma companies seem to be less interested in discussion. This can lead to delays – for example, a big pharma company wanted to move from batch to continuous manufacturing, but it took almost two years for the company to release a polished version of the documentation to the MHRA. Had this been provided at an earlier stage, the 'polishing' could have been carried out in parallel with the discussions, meaning the manufacturing could have begun up to 18 months earlier.
The impact of Covid-19
The coronavirus pandemic and the drive for new vaccines, therapeutics and diagnostics is changing perceptions of what is possible in data gathering and product approval. The push to move products into clinical trials quickly has compelled developers and regulators to discuss projects and seek scientific advice. The MHRA is able to prioritise and support Covid-19 research, and has procedures in place for rapid scientific advice, reviews and approval. Examples of projects that have been able to move faster under the pandemic conditions include the convalescent plasma programme, the approval of the use of remdesevir in certain patient populations under EAMS, and the approval of the Covid-19 Oxford Vaccine Trial in seven working days.
The shape of the existing UK regulatory pathways won't change in a post-Brexit world, but what is not yet clear is whether regulatory approvals will remain linked with EMA, or the MHRA will act as a standalone regulator. The MHRA's guidance updated in February 2020 states that the UK can only act as a concerned member state (CMS) in decentralised procedures or mutual recognition procedures until the end of the transition period. There is still so much uncertainty at the moment, but the aim post-Brexit is for a better-integrated pathway that brings in other agencies in parallel.
It is possible that the MHRA could reduce in importance compared with the Asian and US regulatory agencies, as the UK is no longer the gateway to Europe. However, working in partnership with individual or groups of regulatory authorities could make the MHRA work faster, and be more responsive, innovative and flexible. This would require managing the balance between science and risk.