With a post-Brexit deal agreed, it is time to weigh up the opportunities and the risks for industry. From clinical trials to marketing authorisation, there is much to consider, especially the role the regulator will play. Claudia Rubin dives into the detail.
The Brexit trade deal, welcomed by pharma across the continent, offers plenty of food for thought regarding regulation and trade in our sector, with some as yet unresolved conundrums. Stories emerged early of unintended consequences that, while comparatively small scale, are highly impactful on a personal level. Since the start of the year, British prescriptions are no longer recognised in the EU, so for the handful of epileptic children whose British prescription had entitled them to receive medical cannabis oil from the Netherlands, and doubtless others like them facing similar interrupted supply, the trade deal falls somewhat short.
However, there is no doubting the importance of this trade deal, given how closely linked the EU and UK markets are. There are enormous numbers involved; according to the ABPI, every month at least 45 million packs of medicines are exported from the UK to the EU, and 37 million packs are supplied from the EU to the UK. The UK relies heavily on the EU for its supply of medical devices too, with more than half its £5 billion budget for imported medical technology being spent on devices originating from the EU1.
“There is no doubting the importance of this trade deal, given how closely linked the EU and UK markets are”
Meanwhile, it is no exaggeration to say that the vast UK life sciences and healthcare industry has now entered a whole new era of regulatory oversight.
The Medicines & Medical Devices Bill
Nearing its final stages in parliament, the Bill provides the powers needed to be able to update the current regulatory regime for medicines, devices and clinical trials, in response to the end of the transition period.
The three criteria central to this bill stipulate that regulations must have regard to:
Safety of medicines and devices
The government’s stated approach to the future regulation of medicines and medical devices is largely shaped by patient safety, putting this at the very heart of its considerations. From last year’s report by Baroness Cumberlege2, it is clear that much improvement in the regulation and oversight of medicines and medical devices is warranted. But in setting out our new regulatory regime, a careful balance is to be struck between safety and innovation. The government must be mindful too of not diverging too far from EU requirements; poor alignment may see developers prioritising the EU over the UK market, leading to delays in access for UK patients. The final major issue warranting extensive ethical and practical debate is around patient data; though out of scope for this article, the public needs assurance that their data will be protected and used appropriately.
Availability of medicines and devices
On the second criteria, availability of medicines is clearly fundamental. As with the rollout of the COVID-19 vaccine, all the infrastructure and funding at our disposal counts for little if the product is not available and in the right place for distribution.
Attractiveness of UK
The final piece speaks to the attractiveness of the UK as a major global centre for the life science industry and a favourable place in which to conduct clinical trials or supply medicines and medical devices. It is in this spirit that the UK Medicines and Healthcare products Regulatory Agency (MHRA) has reset itself for this post-Brexit era.
Diving into the detail
During the first week of 2021, the government published extensive guidance on how things will change now that we are officially outside the EU. Covering everything from clinical trials to applying for marketing authorisation, simply digesting the vast quantities of new information is onerous; but what can we make of the relative benefits, opportunities or risks for industry ahead?
Remodelling the MHRA
The government has long insisted that outside the EU, the UK will have ‘the freedom to innovate and cut red tape to speed up the approval process for new treatments’, so transforming the MHRA, making the regulator an enabler of innovation, is a key part of this.
The MHRA has confirmed it will set a 150-day assessment timeline for all new high-quality marketing authorisation applications and has also provided updates on the processes needed to submit changes to marketing dossiers for medicines, as well as for amendments to clinical trials. The UK will have its own orphan status regime – expected to use the same threshold of less than 5 per 100,000; the MHRA will review applications for orphan designation at the time of a marketing authorisation application.
The guidance offers welcome clarity, too, that there are no plans for significant divergence from either the European Medicines Agency (EMA) or the cohort of other regulators, on a large number of matters. It also gives business good time to prepare for these changes, given that existing instruments will remain in place for some time yet. The UK will continue, for example, to recognise the CE marking on medical and in vitro diagnostic devices that have demonstrated their conformity with EU regulation, until July 2023. Meanwhile, since the end of the transition period, our replacement to the CE mark, the conformity assessment – or the UKCA mark, is now available for industry to use for medical devices placed on the market in Great Britain. Whether the UKCA mark will be recognised by the EU is, of course, crucial and, as yet, unclear.
Two very practical areas of deep concern are around the risks of regulatory divergence on medicines and medical devices between Great Britain and Northern Ireland, where key issues re-main unclear and unresolved, with much uncertainty around how the dual systems will work in the future.
The second real concern is how the MHRA is to be staffed and resourced to meet the huge challenges of its future role as the UK regulator of all medicines coming into the UK. It is a much-respected body, but its capacity and expertise will need to be hugely expanded to meet its new obligations and duties. A significant funding boost is surely in order.
“The MHRA is a much-respected body, but its capacity and expertise will need to be hugely expanded to meet its new obligations and duties”
More positively, the MHRA has provided details of its equivalent to the EMA’s ‘rolling review’ process, designed to speed up access to novel medicines. A new licensing and access pathway, which aims to reduce the time to market for innovative new medicines, has been launched, lending some welcome substance to previous verbal commitments to greater collaboration. The Innovative Licensing and Access Pathway (ILAP) developed by the MHRA, should enable better coordination and monitoring of product development activities; harnessing expertise from the MHRA, Scottish Medicines Consortium (SMC), The National Institute for Health and Care Excellence (NICE) and NHS England and NHS Improvement (NHSE&I) in close partnership with drug manufacturers and patients.
The role of NICE
NICE and the SMC will work with the MHRA to consider if a product meets the criteria to be designated as an innovative medicine and be granted an ‘innovation passport’. The ‘passport’ acts as the gateway to the creation of a ‘Target Development Profile’ – a product-specific plan for market entry that should also provide opportunities for enhanced regulatory and other stakeholder input, consideration of impacts on health technology assessment, as well as early engagement with patients.
According to NICE, the ILAP ‘aims to smooth the journey from clinical trials through to NHS patients through closer collaboration and planning’ between the agencies involved in each step, so that NHS patients have access to innovative new medicines sooner. The government makes similar claims; that the new pathway represents a ‘totally new way of thinking’, leading some to question if they should be encouraged or dismayed that good partnership working between industry and the healthcare ecosystem should be considered new thinking.
Taken together with the previous announcement on the UK joining Project Orbis – an international framework for cancer medicines – we could see shorter regulatory timelines, allowing UK patients with cancer to receive earlier access to medicines in future. As the UK BioIndustry Association (BIA) notes, Project Orbis includes the American, Canadian and Australian regulators, and since nearly all innovative oncology products are launched in the USA, this new regulatory path ‘may become a key route by which the UK remains an early and priority market for global launches’, post-Brexit.
Without faulting the approach and optimism, it remains uncertain how this will actually trans-late to faster and more positive approvals by NICE and the SMC. Speeding up regulation with-out solving reimbursement challenges side-steps a fundamental issue.
Building the ‘frictionless pathway’ that so many of us want to see, will certainly be aided by working early with companies on clinical trial design, ensuring optimal data is generated for both regulatory approval and health technology appraisal. NICE also envisages a greater role for the Scientific Advice and Office for Market Access services; though we know that these offerings, while a useful early engagement point for companies, often hold no sway when it comes to crunch time in front of a NICE appraisal committee.
NHSE&I, together with commitment from the Treasury, need to address the reimbursement issue head on, not least to demonstrate that they are living by the spirit of the VPAS scheme.
The aims of stakeholders are aligned; safe and faster access for patients to the healthcare that they need by facilitating smooth progress along the pathway. With the aims not in doubt, the practical considerations are still to be resolved; will potentially faster regulatory approval timeframes mean NICE has to shift its own expectations for completing its work? Will it continue to be able to honour its target of positive approval within 30 days of marketing authorisation? To what extent will it expect to offer more conditional approvals, given the work it will have been involved in with companies at an earlier stage?
Surveying the structural issues
While recognising promising intentions, a sobering recent thought from Nicole Farmer of Sanofi Genzyme is pertinent; that, “with Brexit, the MHRA has a great opportunity to fast-track licences ahead of EMEA, enabling us to start collecting real world evidence to shape access in the rest of Europe, so more people can benefit. However, there is no point racing ahead with a licence if reimbursement is not forthcoming.”
Without this commitment, and reform at NHS England, we risk having a structural problem attracting research and development (R&D), manufacturing and even medicine launches to the UK.
Whether we are talking about vaccines or medical research, the nature of science today is innately collaborative, and it is this collaboration both within industry, as well as between private and public organisations, that enabled truly unprecedented, astonishing science to rapidly to deliver vaccines that may bring the COVID-19 pandemic under control. Positioning the UK as a major life sciences champion requires further partnerships just like these – ones based on mutual trust and close collaboration – to more efficiently connect medical innovations to the patients and healthcare professionals who need them.
Claudia Rubin is Director at Decideum. Go to www.decideum.com