Incorporating Software in Combination with Medical Devices Hardware
Published Dec 04, 2023
Published 24th October 2023
At the recent BIA conference titled “The Future of UK Regulation: driving innovation in the life sciences”, MHRA senior leadership along with key decision-makers, stakeholders and the regulatory community across the life-sciences network, met to discuss latest developments at this time of significant challenge and opportunity. DLRC CEO Dianne Lee, Director of Regulatory Consulting Alisdair Falconer and two other members of the DLRC regulatory team were lucky enough to attend the meeting.
Read on for a summary of the presentations and discussion across the 3 topic sessions:
Following a warm welcome from Steve Bates OBE, Chief Executive, BIA, the Keynote address for the conference was presented by Dr June Raine OBE, Chief Executive, MHRA.
Enabling innovation, to bring transformative products safely to patients, is one of the mission statements of the MHRA, along with facilitating timely access, leading regulatory reform and effective partnership nationally and internationally, while independently regulating in the UK. Dr Raine focused her presentation on MHRA initiatives that support these goals and deliver reliable and predictable operational performance. This included the success of the Innovative Licensing and Access Pathway (ILAP) for medicines and the Innovative Devices Access Pathway (IDAP) pilot phase for medical technologies and solutions, with the future ambition for an integrated innovative pathway for medicines, borderline products, combination products and medical devices. Access to bespoke advice on innovative medicines, devices and manufacturing processes is also available via the MHRA Innovation Accelerator. Dr Raine also noted the imminent release of the MHRA Science Strategy, which will describe priority regulatory pathways to support innovation, aligned with five themes of (i) vaccines and immunotherapies, (ii) biotherapeutics, cell and gene therapies, (iii) diagnostics and genomics, (iv) data science and (v) Artificial Intelligence (AI) and software.
Regulatory reform continues with the Roadmap for Software and AI as a Medical Device, upcoming release of legislation for clinical trials and point of care manufacture and strengthening medical device regulation.
MHRA have also focused on stabilising their performance via data-led triage, priorities led by public health, and training and redeployment of resources to clear review backlogs for variations and clinical trial. With respect to clinical trials, Dr Raine highlighted the Clinical Trials Notification Scheme – a streamlined procedure for certain low risk phase 3 and phase 4 trials which has since been published – as part of a risk proportionate approach to regulation. International recognition and collaborations are supporting delivery of MHRA priorities, such as the new International Recognition Procedure (IRP), Access Consortium, Project Orbis, the International Coalition of Medicines Regulatory Authorities (ICMRA), the International Medical Device Regulatory Forum (IMDRF) and the International Council for Harmonisation (ICH).
Dr Raine concluded by saying that MHRA has changed from a “watchdog” to an enabler, focused on driving innovation from discovery to deployment, ensuring safe delivery for patients, and prioritising operational efficiency combined with regulatory reform.
The first session of the day was chaired by Tim Stonehouse, Vertex Pharmaceuticals and began with a presentation from Lord James O’Shaughnessy, Co-Founder and Senior Partner, Newmarket Strategy on Recommendations from the review into the UK commercial clinical trial landscape. Lord O’Shaughnessy opened his presentation by outlining the difficulty in setting up trials in the UK (UK is the 2nd slowest country in the Europe to set up trials) and recent UK underperformance in clinical trials – the number of industry clinical trials initiated in the UK per year fell by 41% between 2017 and 2021 and the UK has fallen down the global rankings for late-stage clinical research (dropping 2nd to 6th) in phase II studies (and 4th to 10th) in phase III trials in the same period. The time taken to set up and approve commercial clinical trials was significantly faster in both Australia and Spain than in the UK.
However, there is a latent entrepreneurism in the UK – as demonstrated by the success of COVID-19 clinical trials in the UK. The independent review led by Lord O-Shaughnessy resulted in 27 recommendations addressing 8 problem statements with the commercial trial landscape.
1. Reduce the time taken for clinical trial application (CTA) approval, with the goal of achieving 60-day turnaround
2. Develop a comprehensive and mandatory approach to national contracting
3. Increase transparency to real-time data on commercial clinical activity in the UK
4. Establish a common approach to contacting patients about research and giving patients the opportunity to participate
5. Establish clinical trial acceleration networks (CTANs).
An update on progress with implementation of these recommendations is expected to be published in the autumn.
Professor Lucy Chappell, Chief Scientific Adviser And Chief Executive Officer, Department of Health and Social Care & The National Institute for Health and Care Research (NIHR) then discussed “The Future of UK Clinical Research Delivery” and some of the enabling features being addressed to strengthen the UK’s renowned research expertise and leadership in clinical trials.
Based on NIHR data from the last 12 months, recruitment to studies is improving, 69% of commercial studies.
The next presenter in this session was James Pound, Deputy Director, Standards and Compliance, MHRA. Mr Pound outlined the remedial actions being undertaken by the MHRA to get CTA review timelines back on track. These actions include increased resource (phased redeployment from other groups, increased recruitment and training of new and existing staff), improved processes (risk proportionate review – freeing up expert reviewers for complex applications, use of approvals from other regulatory agencies with similarly stringent review to inform MHRA review) and external support (collaboration with NIHR, MHRA external experts on the Committee for Human Medicines (CHM) and Expert Advice Groups (EAGs) and the ongoing development of Faculty of Pharmaceutical Medicines Fellowship initiative). As a result of these changes, MHRA have assessed 418 initial CTAs and 1638 amendments since mid-July, and have cleared the backlog of clinical trial review as of September 2023. The MHRA goal is to offer a sustainable and optimised future for CTA review, where compliant CTAs will be assessed within statutory timelines and performance metrics will be published on a monthly basis. Risk proportional assessment of CTAs according to phase and risk will be implemented, together with triage for submissions, and upstream guidance to avoid common Grounds for Non-Acceptance. MHRA will also continue their focus on communication and system-wide collaboration with stakeholders and partners.
The first session was completed with a presentation on the Perspective from the Health Research Agency by Dr Janet Messer, Director of Approvals, Health Research Authority. Dr Messer gave an overview of what the HRA has been doing with respect to combined review, fast-track research ethics reviews, NCVR, supporting decentralised models, advising clinical research networks (CRNs) on data-enabled recruitment and exploring people-centred clinical research. She also outlined details of what the HRA are currently working on with respect to participant information principles and standards, future clinical trials legislation, equality and diversity, identifying and contacting patients about research, and work on study set-up delays other than costing.
The second session of the meeting was chaired by Kathy Williams, AstraZeneca and began with an introduction to the new international recognition procedure (IRP) to enable access to innovation, presented by Julian Beach, Interim Executive Director, Healthcare Quality and Access, MHRA. From 1 January 2024 the European Commission Decision Reliance Procedure (ECDRP), introduced following the UK’s exit from the EU, will cease and will be replaced by the new IRP, also incorporating the Mutual Recognition/Decentralised Reliance Procedure (MRDCRP). This is a new procedure, and will apply to new Marketing Authorisation Applications (MAAs), and to extensions and variations of marketed products. MHRA has provided a readable and informative introduction to IRP on their website.
A digestible summary of the information available to date on IRP has also be produced by regulatory experts at DLRC here. Mr Beach presented that International Recognition provides an opportunity for reliability and predictability in regulatory review, leading to
IRP will allow MHRA to consider the expertise and decision making of 7 trusted regulatory agencies with equivalent stringency (Australia, Canada, Switzerland, Singapore, Japan, USA, EU) enabling MHRA to conduct a targeted assessment but retain sovereign decision making. Further guidance on eCTD requirements and online IRP eligibility application form are expected to be available within the next few weeks, and MHRA recommended that sponsors intending to submit an IRP application within Q1 2024 should notify email@example.com in order that MHRA can plan resourcing.
The next presentation provided an insight into the implications of IRP for the National Institute for Health and Care Excellence (NICE) and was presented by Dr Nick Crabb, Interim Director, Science, Evidence and Analytics, NICE. Dr Crabb endorsed the opportunity provided by IRP for earlier licensing, earlier patient access and a more attractive UK life sciences ecosystem, but also discussed the challenges for NICE in terms of –
Mitigations already in place and planned to manage these challenges include working with industry to ensure companies notify NICE of filing intentions at the earliest opportunity, new fields in the UK PharmaScan database to reflect IRP, further work on information sharing between MHRA and healthcare system partners supported by improved IT infrastructure, a continued focus on efficiency through the NICE Proportionate Approach to Technology Appraisals initiative, and a request for resources for “surge capacity” to manage the early months of the new IRP routes.
The final two presentations in this session provided perspectives on international recognition from Swissmedic and FDA. Firstly, Jörg Schläpfer, Chief of Staff & Head Sector External Relations, Swissmedic explained that reliance is used extensively at Swissmedic, and this is reflected in strategic priorities and in the culture of the agency. Swissmedic employ reliance procedures for new MAAs, extensions and variations, have mutual recognition agreements (MRAs) in a number of regions worldwide, including the UK, and are participants of both the Access Consortium and the Marketing Authorisation for Global Health Products (MAGHP), in which regional national regulatory agencies (predominantly from the sub-saharan region of Africa) and the World Health Organisation (WHO) are involved in the Swissmedic assessment process.
Shannon Thor, Deputy Director of the Europe Office, Office of Global Policy and Strategy, U.S. FDA then presented on the mechanisms by which FDA support regulatory convergence:
FDA also perform bilateral activities with the MHRA, including a confidentiality commitment (CC), a MRA, international “cluster” groups to exchange information on topics of interest, such as pharmacovigilance, generics, pregnancy and lactation, and Project Orbis.
The third and final session of the meeting was chaired by Dr Martin O’Kane, Novartis Pharmaceuticals.
Dr Camilla Fleetcroft, Strategy & Innovation Director, BSI gave an overview of pro-innovation regulation for the life sciences. Dr Fleetcroft was co-champion for the Pro-innovation Regulation of Technologies Review to advise how the UK can better accelerate development and deploy emerging technology. The ambition of the UK is to become a leader in shaping global regulations and standards in the National Science and Technologies Council’s priority areas. Dr Fleetcroft considered the challenges and recommendations for human health and beyond.
The next presentation was entitled Artificial Intelligence (AI) for drug discovery and clinical development, in which Dr Beatrice Panico, Head of Clinical and Principal Consultant, Scendea shared examples, such as
Dr Panico also advised AI developers to follow rigorous scientific method and access the available guidance on use of AI. Regulators were encouraged to provide clear guidance, international harmonisation and to employ a creative approach.
Professor Alastair Denniston, Consultant Ophthalmologist, NIHR Senior Investigator and Hon Professor in the evaluation and regulation of AI health technologies, Birmingham NHS Foundation Trust and Centre for Regulatory Science and Innovation then presented on the use of AI to improve patient care and provided reflections on AI regulation in healthcare. Professor Denniston outlined the current uses of AI health technologies, such as self-help chatbots, community diagnostics, and decision support systems. He outlined that if we approach AI correctly, we will achieve widespread, rapid 24-7 services that are highly accurate and safe across a diverse population. However, if we get this wrong, we will have highly variable services that are brittle, widely distrusted, and only accurate and safe in majority groups. He considered the growing evidence of patient harm caused or worsened by AI biases and urged transparency and improvement in the inclusivity of representation in health datasets, to mitigate the risk of health inequalities. He highlighted the FDA/Heath Canada/MHRA Good Machine Learning Practice for Medical Device Development Guiding Principles and MHRA guidance on Software and AI as a Medical Device, with a focus on safety.
The final presentation of the day was provided by Dr Janine Jolly, Deputy Director Benefit Risk Evaluation, MHRA, on ensuring the safety of medical products into the future. Dr Jolly outlined the regulatory challenge to manage innovation and access to new treatments versus ensuring patient safety, and highlighted the opportunities for improving safety and surveillance, including:
MHRA believe that the future of safety will be proactive, predictive, personalised, faster and collaborative.
In conclusion, the information shared and discussed by MHRA senior leadership alongside key decision-makers, stakeholders and the regulatory community gave an optimistic view of the UK’s aspirations to regain its prominence as a global clinical research and regulatory leader.
DLRC is excited about ongoing and future progress towards innovative and risk-proportionate regulation and to facilitating access to safe and effective medicinal products and devices in the UK.
DLRC’s experienced consultants are ready to help you navigate the emerging UK regulatory environment: contact us at firstname.lastname@example.org, or use the link below to find how we can support you.