2Research and commercialisation
7.In this chapter we look at the UK’s clinical research landscape, examining basic and translational research and the regulation and the commercialisation of regenerative medicine and cell therapies.
The research landscape
8.Regenerative medicine involves a wide spread of ‘science’, spanning tissue engineering, developmental and stem cell biology, gene therapy and cellular therapeutics, biomaterials such as ‘scaffolds’ and ‘matrices’, nanoscience, bioengineering and chemical biology.12 It was clear from the written evidence we received that regenerative medicine is a developing research field that offers the potential to revolutionise patient care. Advances in regenerative medicine hold the promise of improving methods of disease diagnosis and prevention, and the development of innovative treatments for injuries and illnesses.
9.Cell-based therapies,13 for example, have been approved in the UK for bone marrow transplants (for treating blood and disorders in the immune system). Other stem cell treatments being used, but not yet routinely, include emergency skin grafts (epidermal stem cells) and repairing the cornea of the eye using limbal stem cells.14 Although many stem cell treatments are showing promise in clinical trials, Professor Paul Riley of the University of Oxford highlighted that “a knowledge gap” still exists.15 Professor Anthony Hollander of the University of Liverpool described his research into developing a method of creating cartilage cells from stem cells, making possible the first successful transplant of a tissue-engineered trachea, utilising the patient’s own stem cells.16 His work provided evidence that using adult stem cells could offer solutions for other serious illnesses.
Note: See also paras 95–96 of Sixth Report of Session 2017–19
10.Research by scientists hinges on learning how different biological processes work and applying that knowledge to:
- understand better the causes and progression of different diseases, such as Parkinson’s disease and multiple sclerosis, thereby facilitating better treatments;
- create new biological tools and technologies to accelerate research, drug discovery and medical testing, while also reducing costs and the use of animals; and
- design and develop novel treatments to both enhance natural repair processes and use the abilities of stem cells for replacing damaged, malfunctioning or diseased cells.17
11.Since 2012, research councils have provided £80 million for research on regenerative medicine and supporting technologies.18 This included £25 million provided to support the establishment of the UK Regenerative Medicine Platform (UKRMP) specifically to address key ‘translational’ bottlenecks (paragraph 15) identified in the research councils’ Strategy for UK regenerative medicine in 2012.19 In 2014, £11 million was provided by the Engineering and Physical Sciences Research Council (EPSRC) and the Medical Research Council (MRC) to create three centres for doctoral training.20
12.The UKRMP—a joint initiative by the MRC, the EPSRC and the Biotechnology and Biological Sciences Research Council (BBSRC)21—has established multi-science research hubs across the UK, which produce a variety of tools, reagents and protocols for use by the academic and commercial sectors.22 This initiative has brought together research teams from across 20 universities to help develop new therapeutic approaches.23 It has advanced ‘pre-clinical’ work in areas such as Parkinson’s disease, liver disease, eye disease (age-related macular degeneration), corneal and retinal surgery and joint disorders. The UK Regenerative Medicine Platform (UKRMP) is expected to receive further funding of £17 million from the Medical Research Council (MRC) in 2017 to support programmes reaching clinical testing stage within the next five years.24
13.Regenerative medicine is also an important element of the National Institute of Health Research’s (NIHR) research portfolio. Between 2012 and 2017, it will have provided over £44 million for regenerative medicine research in Biomedical Research Centres and Biomedical Research Units.25 In 2014–15, these research centres had over 150 active regenerative medicine projects, part-funded by the private sector and charitable bodies.26
Basic and translational research
14.Substantial progress has been made in recent years to understand better the underlying biology of cells and of the role of their surrounding micro-environment, which has led to more researchers moving into ‘translational’ regenerative medicine—”the process of applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of human disease”, or ‘bench to bedside’.27
15.Parkinson’s UK highlighted that such research in regenerative medicine is “expensive and offers little in the way of scientific discovery, but is essential if the therapy is ever to go to trial”.28 Translational research is a challenge because of knowledge gaps that remain and the high costs of developing complex and multi-disciplinary therapeutic approaches for which the commercial market is uncertain. The UK is well positioned, however, to undertake clinical development in this field, given the strength of its pre-clinical science and the potential to draw upon high quality research infrastructure (through NIHR) and established capacity in the procurement, processing and distribution of cells and tissues for human application (through NHS Blood and Transplant).29
16.The UKRMP was established specifically to address the translational research agenda. Dr Rob Buckle from the Medical Research Council, one of the Platform’s sponsor bodies, explained that the translational research landscape had changed significantly:
There is a real opportunity around the interdisciplinary mix that has been brought together, and the tools and technologies are in large part now there […] We should be optimistic that there will be good progress in the 10-year time-line but whether that translates to clinical products is an open question.30
The opportunities for translational research were also echoed by Dr Ruth McKernan, Chief Executive of Innovate UK, who told us:
With the continued investment in the UK of research and translation in stem cell science and regenerative medicine, we are one of the leading countries in the world. […] We see more small and medium sized business growing very quickly […] there is an opportunity for us to think globally about how we get ahead of the different steps that are required to really make us a global leading country for cell based therapies.31
17.Despite the focus on ‘translational research’, witnesses saw a continuing need for the more basic scientific research that underpins it. Professor Peter Andrews from the University of Sheffield told us that:
The research councils, the Government and various organisations have clearly put in place the mechanism for translation. Quite a lot of work has been put in place to begin to exploit these opportunities. The real problem is getting the balance between the basic biology that will feed the pipeline into the translation and how to take it forward.32
Professor Jeremy Pearson from the British Heart Foundation voiced a similar concern:
We are at a pivotal stage in the science, which is advancing rapidly, with the potential for real development into clinical efficacy, but […] there is a lot more science yet to be learned to enable that transition to work fluidly across a wide range.33
Professor Paul Whiting, a member of the Medical Research Council’s regenerative medicine research committee, told us that:
Within the UK, we have an outstanding science base in this area. For us to continue to be leaders within this field, we need to continue to maintain that investment in the basic science and translational science—otherwise, our ability to stay in the vanguard in terms of moving that into commercial products is going to severely wane.34
Professor Paul Riley from University of Oxford wanted more emphasis on “a multi-disciplinary approach” which goes beyond the work of the UKRMP in linking together researchers in different fields:
While there is obvious pressure […] to move down a translational pipeline in the context of both [research councils] and charities, [ … ] leaving behind the basic science cannot be allowed to happen. You need something to translate first and foremost. More importantly, you need to understand the mechanisms of what you are actually doing when you go down these therapeutic routes.35
18.Regenerative medicine provides a unique approach to treating diseases and disorders by providing the body itself with the means to repair, replace, restore and regenerate damaged or diseased cells, tissues and organs. Its continual development depends crucially on a strong foundation of basic scientific research. The next Government should work with UK Research & Innovation to achieve a balance of investment in both basic scientific research and the translational research that it underpins, and to identify any research gaps in the light of the significant changes in the regenerative medicine sector over recent years.
Commercialisation
19.The commercialisation of regenerative medicine research depends on the regulatory framework and industry’s capacity to scale-up the therapies involved.
Regulation
20.Regulation of regenerative medicine is complex, reflecting the nature of the technologies involved and their risks. Many regenerative medicine products are governed by the EU Tissues and Cells Directives which outline mandatory standards for using tissues and cells for human applications.36 In the UK, the Human Fertilisation and Embryology Authority and the Human Tissue Authority are responsible for implementing these standards. Other regenerative medicine products are governed by the Community Code for Medicinal Products. Authorisation for clinical trials of regenerative medicines (and of all medicinal products) is governed by EU Directives 2001/20/EC and 2005/28/EC, which are implemented by the Medicines and Healthcare products Regulatory Authority Agency (MHRA). The regulatory framework is intended to ensure that medicinal products used in a clinical setting comply with ‘Good Manufacturing Practice’ (GMP). Lawyers, clinicians, ethicists and other scientists evaluate research proposals to ensure that the use of stem cells is appropriate. If researchers want to carry out new experiments with already-produced stem cell lines, a new proposal must be submitted for approval.
21.Dr Ian Hudson, Chief Executive of the MHRA, explained that the Agency works with those developing products to ensure consistency, quality, safety and efficacy, so that products can be developed appropriately and be licensed.37 The Regenerative Medicine Expert Group identified various aspects of the regulatory framework which required improvement. It called on the MHRA to consider a European classification scheme for regenerative medicine products, to make changes to the ‘hospital exemptions’ scheme which allows for the marketing of unlicensed medicinal products and to incorporate applications for clinical trials approval into the Health Research Authority’s existing Integrated Research Application Systems.38 The MHRA subsequently established a one-stop shop advice service for regenerative medicine. The PHG Foundation (a health policy think tank) complained, nevertheless, that there was still “a lack of central coordination and oversight to streamline the regulatory process and share data, share ‘lessons learned’ from ongoing trials and a central vision driving forward the development of the most promising therapies”.39
22.PHG Foundation told us that “the regulatory environment was not being consistently applied in the field of ‘advanced therapy medicinal products’ (ATMPs)”.40 These emerging technologies and therapies are based on genes (‘gene therapy’), human cells (‘cell therapy’) and tissues (‘tissue engineering’) and are regulated by the EU.41 The EU Directive requires ATMPs to obtain authorisation from the European Medicines Agency before they can be placed on the market.42 Because ATMPs are complex therapeutic products that require specialist manufacture, storage and distribution, there were only 20 approved ATMPs worldwide as at 2016.43
23.Current EU regulations allow for exemptions where products can be made on a non-routine basis without market authorisation. A ‘hospital exemption’ allows an ATMP to be manufactured for use by doctors in a hospital setting to meet the needs of particular patients. In the UK, there is also a so-called ‘specials’ exemption scheme which allows further flexibility. The regulatory landscape has changed in response to the development of new drugs. Through the MHRA’s Early Access to Medicines Scheme, drugs are made available to patients before they have gained full licence approval.44 Such adaptive licensing also allows drugs that have received initial approval for use by a defined group of patients to then go on to be used on larger populations.
24.Although the exemption system is a potentially life-saving process for some patients, some witnesses had concerns about possible inconsistency and the implementation of the exemptions. Genetic Alliance UK told us that the “impact of these schemes on patient access to advanced therapies […] is unclear”.45 The Association of the British Pharmaceutical Industry (ABPI) also raised concerns about the hospital exemption, arguing that “there was no uniform interpretation of the term ‘non-routine’, leading to different implementation of the exemption by different Member States”.46
25.It is important that the regulatory environment for regenerative medicine remains flexible to accommodate new and diverse approaches while also maintaining robust review processes to ensure that the most promising, effective and safe therapies are made available to patients. The MHRA have taken forward the Regenerative Medicine Expert Group’s recommendations on providing a central focal point for regulatory advice, but there is more to be done.
26.The next Government should review how regulatory ‘hospital exemptions’ are used for Advanced Therapy Medicinal Products across the UK, to assess how EU ATMP regulations might be adapted for the UK post-Brexit in order to reflect our own perspectives on the optimal balance between safety and accelerated access to cutting-edge technologies.
Opportunities for manufacturing
27.There are also non-regulatory challenges for the manufacture and supply of regenerative medicine products, including the complexity of some manufacturing procedures and the difficulty in scaling-up processes. The Academy of Medical Sciences told us that:
Further infrastructure needs to be prioritised to enable affordable access to appropriate manufacturing facilities at GMP standards, particularly for academia and SMEs. Currently these facilities are not available at sufficient scale in the UK, and researchers need the source material from the EU and US manufacturing centres, generating further cost and regulatory challenges.47
28.Ian McCubin of GlaxoSmithKline, and co-chair of the Advanced Therapy Manufacturing Taskforce, explained that:
The nature of these products is that they are moving quickly and within one or two years, they will be much more common.[…] SMEs are growing, but they will hit a tipping point quite quickly where they have to make their mind up about whether they invest in manufacturing capability here or go somewhere else. We have to make sure that, when they reach that point, they do it here and the mechanisms are in place.48
University of Bristol told us that:
A major barrier to progress is the paucity of funding of GMP manufacture of novel therapies for use in Phase 1 clinical trials […] A further imminent national problem will be that of Phase 3 trials. These multi-centre trials […] are extremely expensive and far much beyond the scale of the MRC, NIHR or charities.49
29.To support the growth of regenerative medicine, Innovate UK established the Cell and Gene Therapy Catapult in 2012. In 2014, the Chancellor announced further funding to create a UK Cell Therapy Manufacturing Centre, scheduled to open in 2018. This will be managed by the Catapult.50 Statistics published by the Cell and Gene Therapy Catapult show that investment in the cell and gene therapy industry in 2015 was over £400 million compared to £35 million in 2012.51 Witnesses welcomed the Catapult’s work in helping to bridge the gap between translational research and the manufacturing of cellular and regenerative medicine therapies. Dr Rob Buckle from the Medical Research Council believed that “the Catapult’s role is to commercialise. It is a company and therefore the demarcation between academic research and how it crosses over into the Catapult is reasonable. […] It is a good pipeline and model”.52 Professor Jeremy Pearson of the British Heart Foundation believed that the Catapult was “in the right space to assist that transition as and when it occurs, but it has not quite got there yet. It is a valuable piece of the ecosystem”.53 While the Academy of Medical Sciences told us that the Catapult provided helpful guidance, they believed that “on occasion, the cost implications and limitations in capacity for the [Catapult] to provide guidance can mean that further advice needs to be sought elsewhere”.54 Professor Anthony Hollander of University of Liverpool expressed similar views:
It is hugely valuable to us on the one hand as an expertise resource. On the other hand, I think that in future it will help us collectively to figure out how we scale up commercially and turn the discoveries into something that can reach larger numbers of people. I am not sure the model is perfect yet. The Catapult is still developing its own self vision, but we are getting there.55
30.The size of the advanced therapies market has been estimated at $10 billion by 2025 for individual product classes such as Gene Modified Immune Therapies or Ex-vivo Gene Therapies, up to $67 billion per annum by 2020 for the industry as a whole.56 The key commercial challenge for companies seeking to tap that market is working out how Advanced Therapy Medicinal Products [ATMPs] will fit into European healthcare systems and how they will be paid for by healthcare funders or users.57 Innovate UK told us:
ATMPs promise to be highly disruptive to the current clinical treatment setting and systems. Establishing efficient and successful delivery and administration to patients may best be served through established specialist centres in the UK and may require the design and funding of new clinical centres to accommodate these new approaches.58
31.In September 2016, the Advanced Therapy Manufacturing Taskforce published an Action Plan, which included:
- securing an internationally competitive fiscal landscape to attract investment;
- capturing investments through a proactive and targeted marketing approach and simplifying the process of engagement between investors and Government;
- capturing internationally mobile investment through capacity and capability growth in the UK;
- setting out an end-to-end talent management plan to secure the relevant skills for emerging manufacturing technologies;
- setting out a swift, predictable and viable route-to-market for these innovative products and giving industry confidence that the UK is a progressive global hub; and
- developing a long-term regulatory strategy and plan for the MHRA to lead in global standards.59
Jo Johnson MP, minister for Universities, Science, Research and Innovation, believed that the action plan will provide valuable input to the Industrial Strategy, stating in November 2016 that “life sciences, and within that advanced therapies, hold great potential for the UK to develop new sources of economic competitiveness”.60
32.In April 2017, Business Secretary Greg Clark MP announced the Government’s commitment of over £1 billion to the Industrial Strategy Challenge Fund, which we examined in our recent report on the industrial strategy.61 That new commitment included £197 million over the next four years to develop first-of-a-kind technologies for the manufacture of medicines that will speed up access to new drugs and treatments.62
33.The UK life sciences sector is a pioneer in the clinical development of new regenerative medicine therapies and well placed to create new high-tech high-value manufacturing businesses around these advanced therapies. Regenerative medicine researchers, however, need manufacturing support for ‘translating’ their work, and the Cell and Gene Therapy Catapult is working to bridge the gap between ‘translational’ research and commercialisation. The Catapult should nevertheless extend its support more widely, to make it available to both experienced and new innovators in the regenerative medicine sector.
34.In order for regenerative medicine to attract commercial interest, companies must have the confidence that their investment will generate a return. Potential barriers to commercial investment remain, including uncertainty over the ability to patent cell-based products, and the need for expensive development of Good Manufacturing Practice (GMP)-quality products before testing on patients. The British Heart Foundation emphasised that these must be addressed if regenerative medicine is to have a wide-reaching impact for patients.63 NHS market access and reimbursement arrangements are perhaps, however, the most critical factor for manufacturers being able to supply treatments which are both profitable for the supplier and affordable for the healthcare system.64 Keith Thompson from the Cell and Gene Therapy Catapult explained that there are business-related barriers in understanding the influence of ‘health economics’:
It is no good saying “my product is special, give me a special price”. The price is only ever going to be the health benefit and therefore you have to be able to make that product within what the reimbursement price is.65
35.We discuss the barriers to the NHS adoption of regenerative medicine therapies in more detail in Chapter 3.
12 BBSRC, EPSRC, ESRC, MRC and Technology Strategy Board, A Strategy for UK Regenerative Medicine (2012)
13 Cell based therapies work via stimulation of endogenous repair through extracellular factors or differentiation and functional replacement of endogenous cell types, which include stem cell transplantation or infusion to treat hematopoietic diseases, cardiac conditions and Parkinson’s disease.
14 Centre for Regenerative Medicine, ‘What are stem cells?’, accessed 24 April 2017
15 Q19
16 Qq80–82
17 Centre for Regenerative Medicine, What are stem cells?, accessed 24 April 2017
21 UK Regenerative Medicine Platform, ‘Future of regenerative medicine looks bright with new funding boost’, Press Release, March 2017
22 UK Regenerative Medicine Platform, ‘Future of regenerative medicine looks bright with new funding boost’, Press Release, March 2017
23 UK Regenerative Medicine Platform, ‘Future of regenerative medicine looks bright with new funding boost’, Press Release, March 2017
24 UK Regenerative Medicine Platform, ‘Future of regenerative medicine looks bright with new funding boost’, Press Release, March 2017
27 Office for Translational Research, University of Cambridge, ‘What is translational research?’, accessed 24 March 2017
29 Q75 [Dr Rob Buckle]
30 Q54
31 Q151, Q153
32 Q10
33 Q57
34 Q101
35 Q13
36 Safe human tissues and cells for transplantation—(2004/23/EC, 2006/17/EC and 2006/86/EC), January 2016
37 Q93
38 Regenerative Medicine Expert Group, Building on our potential: a UK pathway for regenerative medicine (December 2014)
41 The aim of ATMP regulation was to offer a consolidated regulatory framework for innovative medicines and it was designed to ensure the free movement of these medicines within the EU, to facilitate their access to the EU market, and to provide incentives to European pharmaceutical companies in the field, while guaranteeing the highest level of health protection for patients.
42 EU Directive 2001/83/EC as amended by the ATMPs Regulation 1394/2007
44 Medicines and Healthcare products Regulatory Agency, ‘Apply for the early access to medicines scheme (EAMS)’, accessed 24 April 2017
48 Qq158–159
51 Cell and Gene Therapy Catapult, ‘Investment in cell and gene therapy industry in the UK grows 10x since 2012 to £400m/per year’, Press Release, 21 September 2016
52 Q70
53 Q63
55 Q63
59 Medicine Manufacturing Industry Partnership, Advanced Therapies Manufacturing Action Plan, (November 2016)
60 Association of British Pharmaceutical Industry, ‘Action plan for UK to capture the next generation of medicines manufacturing jobs’, Press Release, November 2016
61 House of Commons Science and Technology Committee, Thirteenth Report of session 2016–17, Industrial Strategy: science and STEM skills, HC 991
62 Department for Business, Energy and Industrial Strategy, Business Secretary announces Industrial Strategy Challenge Fund investments, Press Release, April 2017
65 Q156
28 April 2017