The Chequers summit on 6 July and the subsequent resignation of ministers illustrates how controversial it is to decide whether the UK should share a “common rule book” with the EU after Brexit, or set up its own independent regulators. In this blog, Derek Hill looks at the regulation of medicines and medical devices as examples of the thin margin of action that the UK has to innovate and transform its regulatory landscape in the health sector.
The UK has a strong tradition in life-sciences, including in developing new medicines and medical devices to help improve healthcare. Pharmaceutical companies have been among the most successful UK companies. Medicines and medical devices are very highly regulated. Many of these regulations are essential for protecting patients, but they also slow down innovation. With the UK on course to leave the European Union at the end of March 2019, it is important to assess the relative merits of the UK remaining closely tied to the EU’s regulations for medicines and medical devices, or to diverge from EU regulations to catalyse innovation in products that could benefit patients and help grow businesses.
For example the cabinet minister Michael Gove has argued the great British success of the pharmaceutical industry is “held back by the principles of the Clinical Trials Directive”. Former life science minister, George Freeman, makes case for a Brexit that will counter ‘anti-science’ politics in the EU. As an example, he looks at the rapidly growing area of digital health where he argues old regulatory silos can stifle innovation.
Could leaving the jurisdiction of EU clinical trial regulations and medical device regulations lead to a renaissance in innovation in medical drugs and technology that could strengthen the UK life science sector?
The relevant regulation for the development of new medicines used to be the Clinical Trials Directive (which Gove referred to in article above) but this is now superseded by the Clinical Trials Regulation. For development of new medical devices, including digital ones that might be mobile phone apps, the applicable European regulation has been the Medical Device Directive, which is now being superseded by the Medical Device Regulation. As is the case in many sectors, the EU regulations are not stand alone. The clinical trial regulation is based on an international harmonisation effort on Good Clinical Practice based on thirteen core principles (ICH-GCP principles). It is hard to see the UK arguing that it should move away from ICH-GCP principles. The basic way the clinical trials are conducted worldwide (and big trials are always in multiple countries) is harmonised. The UK would have limited ability to change this.
What opportunities could regulatory divergence provide?
What people often complain about with EU medicine regulations is their lack of clear guidance on what success looks like, their vague feedback on trial design, the complexity of submitting data, and the hurdles for first in human studies.
There is scope for regulatory innovation, and the UK legacy medicines and medical devices regulator, the MHRA has lots of great regulatory scientists who will be freed up from their current duties with the European Medicines Agency if and when the UK ceases to be involved in the EMA. For small or medium sized clinical trials, the UK could provide a faster track for GCP compliant “proof of concept” studies of new treatments.
But how significant would this innovation be? The NHS is an unattractive market (it pays less for drugs than just about anyone else) so the motivation for companies doing trials in the UK wouldn’t be about fast access to NHS. Making the UK regulatory environment slicker is only one factor in attracting “proof of concept” drug trials. Speed of conducting trials (in particular, how good are doctors at recruiting patients) is critical. In many disease areas, the UK is not the best and can also be relatively expensive. Data collected in the UK would also need to be usable in submission to other regulators (EMA in EU, FDA in USA). The UK could thus provide success in niches, but it is not (yet) clear this could drive the sort of inward investment needed to “move the dial” on the UK economy.
What about the need to innovate in regulation of digital health technologies?
Digital Health has been predicted to transform healthcare – re-engineering the relationship between patients, doctors and drug healthcare businesses. Could the UK set up a regulatory framework that makes the UK a world-leading place to develop digital health technologies?
It is once again important to be aware of the international context. The EU and US used to quite different regulatory environments for medical devices, especially for devices that were largely software. Many devices were only available in one market. However, the new EU medical devices regulations address many criticisms of the EU system, and also bring it closer to the US FDA. More significantly, the International Medical Device Regulators Forum, which the US (FDA) and the EU (through the commission) are active participants in, is now having real influence. The IMDRF membership includes key markets (USA, EU, Brazil, China, Australia, S Korea, Russia etc).
More particularly, the Software as a medical device (SAMD) working group of IMDRF, chaired by the FDA, has been highly innovative in its approach and is having rapid impact in the harmonisation of regulatory guidance. The EU gave significant input into the IMDRF SAMD guidance documents to maximize alignment with the medical device regulations. More remarkably, the FDA produced a Software as a Medical Device guidance in November 2017 that was lifted entirely from the IMDRF recommendations. More radically, the FDA is also entirely re-engineering the way their medical device approval process works for digital technologies, with the “pre-cert” programme, being piloted by companies including Apple and Google, which also building significantly on the IMDRF framework.
Regulations are then nothing like static. Regulatory innovation is rife in the EU and the US, especially in digital areas. The UK does have a reasonable digital health start-up environment but the British market (largely the NHS) is relatively small. And if UK regulations were to diverge too much, then data collected in UK won’t support approvals in bigger markets. A careful line has to be trodden to make the UK attractive.
Could combinations of digital technologies and medicines be an area where UK regulatory innovation could be transformational?
This is definitely a potential high growth area. There are numerous options to combine drugs and digital technologies together to provide safer and more effective treatments. For example, combinations of anti-depressant drugs and computerised “talking therapy” could provide better treatments for depression. This is an example of what regulators call “combination products”. In both the EU and the US, the developer of the product has to agree with the regulator whether the primary mode of action is the drug, or the device. If the primary mode of action is the drug, then you go through the drug regulator (EMA in Europe, FDA CDER in US). If the primary mode of action is the device, then you go through the device regulator (the Medical Device Regulation in the EU, FDA CDRH in the US). As combinations of drugs and digital technologies become more mainstream, these regulatory “silos” could become an increasing problem.
Could the UK use an independent regulatory environment to provide a dedicated regulatory path for digital combination products? That is certainly a possibility – though one that needs to be worked up in detail. But any regulatory innovation in the UK will be competing with digital health regulations innovation in bigger markets. Given the momentum the IMDRF is having in this area, and that this is being rapidly being translated into EU and US guidance, there is perhaps less opportunity to take away the old silos than there might have been a few years ago.
Independent UK regulations for drugs and medical devices do provide potential opportunities to encourage innovation in new treatments in the UK, but they so far seem limited. To the author’s knowledge, there is not yet a detailed case being made to show these could compensate for a loss of influence in the regulation of the much larger EU market. That explains why trade bodies would prefer the UK to remain aligned with the EU.
Derek Hill is Professor of Medical Imaging Science at UCL.