Richmond Pharmacology – Written evidence (LSI0046)
This submission constitutes Richmond Pharmacology’s response to the Lords Select Committee on Science and Technology call for evidence into Life Sciences and the Industrial Strategy. We have divided our response into numbered sections which correspond to questions in the Call for Evidence.
About Richmond Pharmacology:
Richmond Pharmacology Ltd is a research institute with a global reputation for excellence in clinical research. Founded in 2001, we are the leading Early Phase full-service Contract Research Organisation (CRO) in the country. Richmond conducts approximately 10% of all Phase I studies performed in the UK and 1 in every 100 studies worldwide. Richmond’s clinical trials are often complex and cutting edge and conducted in important disease areas, including oncology and amyloidosis. Currently based at our state-of-the-art clinical research facility by the campus of Guy’s Hospital and Kings College London, we have worked with NHS partners to conduct between 15 and 20 clinical trials per year, amounting to over 300 studies in London since 2001.
As a fully MHRA-accredited CRO, our 100 skilled staff carry out clinical studies to the highest ethical and medical standards. Our interaction between clinical and academic specialists in their respective fields and over 250,000 volunteers, patients, and patient groups, ensures our research meets the highest regulatory, scientific and ethical requirements. Our research capabilities are extremely broad, and we specialise in Japanese Ethnic Bridging studies, TQT and Adaptive Phase 1/2a studies. Richmond is also a good corporate citizen, funding academic research and publications, creating jobs in the local community and contributing to the work of its stakeholders. Over the last 15 years we have made a net contribution of 7% of our cumulative turnover to the NHS. The company is a prominent stakeholder which actively and very successfully promotes UK life sciences globally with our client base of biotechnology and pharmaceutical companies in the UK, Europe, Japan and the US.
1 SUMMARY
1.1 Richmond Pharmacology plays a crucial part in the life sciences skills ecosystem, providing a platform for world-class research to take place while also contributing to international research efforts.
1.2 Our departure from the EU means we lose many elements that make up a highly favourable environment for our business to operate in, particularly with respect to two key factors:
1.3 It is of particular importance that the UK’s capability in Phase I trials is protected and expanded to ensure the global competitiveness of the industry. This is especially the case given the dwindling number of Phase I units in the UK, which means the country is also likely to miss out more often on later phase trials for potentially revolutionary drugs, given First in Human studies often lead to successive research in the same country.
2 ENSURING SKILLS FOR THE FUTURE
Q3: What can be done to ensure the UK has the necessary skills and manpower to build a world class life sciences sector, both within the research base and the NHS?
2.1 As the UK’s leading Phase 1 clinical trials organisation, we are acutely aware of the need for access to highly skilled labour to support the continued growth of the life sciences sector, within the research base and NHS.
2.2 To that end, we are firmly supportive of the recent Life Sciences Strategy which called on the Government to establish a migration system that allows the recruitment of the best international talent. We, along with the wider sector, are strongly reliant on international workers and therefore it is vital that the Government ensures that future agreements with both the EU and non-EU countries allow for skilled workers to continue to move to the UK to play a key role in supporting our sector.
2.3 Over 40% of our staff are from overseas and Richmond also has an experienced in-house Japanese team, including a Japanese GMC registered doctor, nurses, study managers and recruitment staff who are essential to the running of our trials.
2.4 In terms of ensuring we have access to the required workforce, we are also firmly supportive of increased funding and opportunities made available to build the skills base within the UK. The Life Sciences Strategy’s proposals to create an apprenticeship scheme that focuses on data sciences and skills across the life sciences sector is also most welcome.
2.5 We would also urge the Government to conduct a full assessment of the skills base required to allow the UK’s life sciences sector to continue to flourish, including through engaging in open dialogue with key industry stakeholders including ourselves.
2.6 Richmond Pharmacology has so far provided opportunities to just under 200 life sciences graduates and 50 medical doctors.
2.7 Richmond are firmly committed to driving forward the life sciences sector in the UK, and to continuing the specialist training of staff, thus helping the UK’s workforce to become highly skilled and an even more attractive proposition for clients and investors worldwide.
3 THE UK IN A GLOBAL CONTEXT
Q4: How does the UK compare to other countries in this sector, for example Germany and the United States?
3.1 The UK is currently the only country offering a truly helpful and novel approval pathway that speeds up development and reduces cost.
3.2 The MHRA’s accredited Phase I Clinical Research Organisations (CROs) in the UK today offer unrivalled research excellence to biopharmaceutical companies who want to outsource the first phases of their new drug trials, especially First in Human Studies.
3.3 This is predominantly due to the flexible regulatory system operated by the MHRA which helps make trials more efficient, maintaining a safe environment for trial participants while reducing maintenance costs and streamlining the regulatory process.
3.4 The fundamental difficulty in designing Phase I studies is that the ability to predict human response and safety is riddled with uncertainty. Ideally, trial sponsors want to learn from the data as it emerges and to respond to new information immediately to amend the protocol.
3.5 Since 2008, the MHRA has approved numerous and increasingly complex adaptive early phase studies which outline a concept study plan including a detailed management plan highlighting how the study is to progress, and how changes are controlled and approved. These studies were conducted safely but also save many months of development time [Lorch et al. Eur J Clin Pharmacol. 2012].
3.6 Adaptive designs can be best exploited in combined “integrated” protocols, whereby an entire early phase programme from First-in-Human to Proof of Concept is performed within one trial protocol following a single regulatory and ethical approval.
3.7 This approach allows companies to run protocols of greater complexity faster and is more cost effective than conventional approaches. However, this requires specialist skill in planning and conduct, and above all regulatory agencies and ethics committees capable of reviewing these projects – all of which the UK currently has.
3.8 More broadly, the UK’s regulatory environment is effective in ensuring the efficient, fast and safe conduct of adaptive combined trials. The MHRA’s Scientific Advice service is easily accessible and highly transparent, while the review of applications for Clinical Trial Authorisation by the MHRA and ethics committee is fast and predictable.
3.9 Approvals can be expected within 28 days, and there are efforts underway to streamline the process even further to improve competitiveness.
3.10 With regards to our own business, the appeal of integrated protocols, in addition to the flexible and innovative regulatory environment, has already attracted considerable interest from biotech companies in the US and elsewhere, most notably in Cambridge and Boston, Massachusetts.
3.11 We were pleased that the Life Sciences Strategy emphasised novel and complex trial designs as a priority post-‘Brexit’, and we would urge the Government be increasingly active in supporting early development CROs to promote this research excellence across the world.
3.12 By way of contrast, while the EU currently provides a very favourable regulatory environment for drugs licensing and medicines safety, early phase clinical trials are highly regulated across the world. Approaches by regulators outside of the UK have resulted in more restrictive and inflexible regulatory oversight and often considerable bureaucracy to perform safe studies in early drug development.
3.13 Phase I studies have also attracted negative publicity from the Tegenero/Parexel incident at Northwick Park Hospital in 2006 and the more recent incident in France involving Bial and BioTrial leading to the death of a participant. This resulted in calls for even more regulation.
3.14 The resultant lack of flexibility and increased cost from greater regulation have also placed a burden on investigators and sponsors to conduct exploratory studies efficiently. Regulatory requirements range from requests to submit single protocols only or, in cases of integrated protocols with some “alternative pathways”, the submission of interim data before approving subsequent steps. This results in even greater bureaucracy, delays and increased cost.
3.15 Many countries have tried to address this by offering shorter approval timelines for Phase I studies, but the regulatory environment in the UK continues to represent best practice. It is crucial that this industry-leading approvals process is maintained.
4 IMPACT OF BREXIT ON THE LIFE SCIENCES SECTOR
Q16: What impact will Brexit have on the Life Sciences sector? Will the strategy help the sector to mitigate the risks and take advantage of the opportunities of Brexit?
4.1 The concerns of the impact of Brexit are well documented elsewhere, so here we have focused on the three key areas for our business: the clinical trials environment, the shortage of qualified staff, and the UK’s lack of influence over future regulation.
4.2.i Clinical trials environment
4.2.ii The UK’s decision to leave the EU has already prompted concerns and uncertainty over how British biopharmaceutical services can compete globally, especially if single market membership and EMA regulations are not part of the Brexit deal. This uncertainly has proved particularly damaging, with sponsors dropping out of trials and deciding not to invest in the UK.
4.2.iii The negotiated relationship between the EMA and the MHRA will determine the commercial attractiveness of the UK for investment and the speed of clinical trials authorisation. Currently, the EMA is based in London, which gives the UK – through the MHRA – increased influence over its policy direction. In return, the EMA benefits from the MHRA’s expertise. Brexit endangers this as the EMA will be moving to another EU country, and consequently weaken the view of the MHRA as a life sciences hub.
4.2.iv While we welcome the assurances from Secretary of State Jeremy Hunt that the MHRA will continue to work closely with the EMA, it is vital that the nature of this relationship moving forward is clarified as soon as possible so that the sector can make ongoing investment decisions with a degree of certainty. We would urge that the Government treats this issue as a priority in its negotiations.
4.2.v Currently, the UK is the most popular location for Phase 1 clinical trials in Europe, second for Phase 2, and third for Phase 3; this privileged position is unlikely to continue if the UK must enact separate verification in addition to the existing European authorisation. While the present EU Clinical Trials Directive (CTD) is seen as stiflingly bureaucratic and over-cautious, the UK has played an instrumental role in the forthcoming 2018 reforms which seek to better balance innovation and risk. In exiting the EU, the UK will no longer benefit from the improved, streamlined portal which it heavily influenced.
4.2.vi It is essential that applications for authorisation of Early Phase clinical trials and their maintenance through the portal and database are as fast, easy and efficient as the equivalent process in Europe. We need reassurance that access to the portal is a priority in the negotiations, and clarity on the cost of access to it after Britain leaves the EU.
4.3.i Workforce
4.3.ii As outlined in Section 2, there is also a significant need to ensure that Britain’s decision to leave the EU and the current deal agreed does not limit access to skilled workers from overseas. The UK is reliant on migrant labour to attract the requisite talent for research and innovation.
4.4.i Role of the MHRA
4.4.ii The MHRA has played a major role in securing the uniquely flexible regulatory environment in the UK today, and this is in part due to its influence and reputation within the EMA. Therefore the Government should seek to emphasise Phase I research in the UK as very appealing to international customers, such as large Pharma, replicating the current environment which allows innovative practices to speed up trials and reduce maintenance costs.
4.4.iii. Richmond would therefore urge the Government to prioritise having the closest possible relationship with EU research agencies, especially the EMA. The MHRA currently enjoys a heavily influential role on the EMA’s various committees and this must be allowed to continue if the UK’s life sciences sector is to continue to prosper.
4.4.iv While there are undoubtedly some big questions left to answer over Brexit, there is still a significant opportunity for the Government to promote the UK’s excellence in early phase clinical research. The recent publication of the Government’s Life Sciences Strategy did provide some reassurance through the commitment to increased R&D spending and the focus on increasing the number of clinical trials in the UK over the next 5 years by 50%.
5 THE REGULATORY ENVIRONMENT AFTER BREXIT
Q17: How should the regulatory framework be changed or improved after Brexit to support the sector?
5.1 We fully support the Government’s ambition for London to be viewed as the global hub for Life Sciences. Richmond is committed to continuing to work in the capital long-term to help make this a reality.
5.2 As the Life Sciences strategy correctly identified, and we have explained in section 4, the MHRA has been instrumental in shaping the favourable regulatory environment of the EU today. We would urge the Government to continue to support the MHRA’s excellent international reputation for innovation and leadership in this field, particularly in its work in streamlining the approvals process.
5.3 It is imperative to the success of the Life Sciences Strategy that the future regulatory environment in the UK should seek to prioritise patient safety while remaining sufficiently flexible and efficient to attract pharmaceutical investment.
6 INVOLVEMENT WITH EU AGENCIES
Q18: To what extent should the UK remain involved with and contribute to agencies such as the EMA post Brexit?
6.1 As emphasised in previous sections, Richmond would welcome the closest possible relationship with EU research agencies, especially the EMA. The MHRA currently enjoys a heavily influential role on the EMA’s various committees and this must be allowed to continue in whatever vein.
6.2 A close alignment between the EMA and our domestic counterpart, the MHRA, will smooth the transition and encourage confidence in the UK clinical trials market. Therefore protecting a significant revenue stream for the UK and allowing the life sciences sector to continue to grow.
7 CONCLUSION AND RECOMMENDATIONS
7.1 We need more central backing from the Government to help promote the early-phase clinical trials industry’s development abroad.
7.2 In particular, large pharma companies should be encouraged to place these studies in the UK over the US and EU.
7.3 Large pharma companies often rely on outsourcing and a case should be made to move away from their preferred alliances with global CROs, which have copied the traditional inflexible pharma set-up, to the more nimble and flexible UK market where a higher degree of competence is available in a well-regulated safe environment.
7.4 There are numerous benefits from customers choosing to have their early drug development in the UK, and not just from an economic viewpoint.
7.5 If Phase I trials are successful, it is typically the case that further studies (testing medicines on patients for example) are conducted in the same country. This knock-on effect also benefits the broader UK life sciences industry, with increased inward investment being made in the sector to support early phase trials.
7.6 While the Government has looked to promote the UK’s life sciences industry as a whole, we believe there is significant merit in focusing promotion on Phase I trials as a marketing tool for the broader industry.
7.7 As a leading Phase I CRO, we would welcome discussions with Government to discuss how best to market Phase I trials to customers abroad and make the most of our leading competitiveness to attract greater foreign investment.
15 September 2017