Sarah Cartmell is a Professor of Bioengineering at The University of Manchester and is currently Head of the Department of Materials which is home to nearly 2,000 students and staff. In this blog, Sarah explores why it can take so long for biomaterials to get from the laboratory to being used by patients and highlights the action required from regulators, researchers and clinicians to redress this problem.
- While the UK is extremely successful in the development of biomaterials, it is less successful when it comes to getting these translated quickly into products available for use.
- There is still not enough translation of innovative biomaterials into commercial and clinical products.
- The needs of patients and clinicians must always be addressed and focus should not just be on the push of new technologies.
- With changes from the regulators of biotechnology and researchers, the biomaterials sector has a great opportunity for increased productivity, leading to more innovations and greater benefit for patients.
Biomaterials are integral to a huge number of medical technologies. These are the advanced materials introduced into our bodies: artificial hips, bone grafts, heart valves, pacemakers, catheters, stents, enamels, fillings and many more medical devices contain highly-specialised biomaterials. With a rapidly growing and ageing population, the UK healthcare system needs to make the best possible use of biomaterials to provide cost-effective interventions that will help to meet this challenge. But why does it take so long to get from lab to patient, and what’s holding us back?
Research success vs commercial success
The global market for biomaterials is estimated to be worth $70 billion (2016) and is expected to grow to $149 billion by 2021. Within the UK, the medical technology sector has doubled since 2009; it is the sixth largest in the world and third largest in Europe, with a turnover of £21 billion per year.
However, while the UK is extremely successful in the development of these materials, it is less so when it comes to getting these translated quickly into products available for use. In the Times Higher Education World University Rankings, UK universities rank first and second worldwide in Research (which measures research volume, income and reputation); but the highest UK ranking in Impact in Industry, Innovation and Infrastructure, which focuses on universities’ role of fostering innovation and serving the needs of industry, is 11th. This was highlighted to us just last year by Dr Edward Draper, the Chief Executive Officer of Ortheia, at the SME accelerator day at the Henry Royce Institute.
The knowledge gap and new innovations in Manchester
A major contributor to this lack of success has, I believe, been insufficient knowledge of the stringent regulatory requirements necessary to get new biomaterials from the laboratory to the clinic, ensuring patient safety. Within The University of Manchester, this issue has been recognised and steps are being taken to tackle it, with teams taking exciting new biomaterials ideas into clinics and commercial ventures. This includes new materials to treat nerve damage, peptide based hydrogels for cell culture and colloid gels designed to treat chronic back pain resulting from disc degeneration.
The University of Manchester’s Professor of Biomaterials, Julie Gough, and Dr Adam Reid, a senior Clinical Lecturer in Plastic and Reconstructive Surgery, provide one example of this. They have developed a pioneering new treatment for peripheral nerve damage resulting from traumatic physical injury, where standard surgical techniques prove unsuccessful. Their innovative solution is the development of Polynerve, a biodegradable polymer nerve conduit (a kind of bandage to aid healing). This is essentially a small tube attached to either end of the severed nerve, designed to aid the healing by guiding the re-growing nerve, while breaking down and being absorbed by the body during this process. Although the concept of nerve conduits is not new, techniques developed by Professor Gough have been able to create a microgroove patterning on the internal surface of the conduit, which was previously not possible. Research conducted by Professor Gough and Dr Reid have shown that these microgrooves provide tracks, which guide the regrowing nerve cells across the ‘nerve gap’ between the severed ends of the damaged nerve, accelerating repair. Polynerve is currently being used to treat 17 patients in a Phase I clinical trial in Manchester, which will determine its safety and efficacy of the micro-grooved conduit.
Vital learning & new ventures
Through the course of this work, Professor Gough and Dr Reid learned what is required to safely translate a truly innovative idea from a proof of concept and discovery in the laboratory, to determining whether this idea improves patient outcome. This is a complex process, comprised of multiple stages designed to ensure patient safety at every step of the manufacturing and treatment process, requiring specialist knowledge of the material, its manufacture, the surgical techniques required to utilise it and the legal framework determined by the government to protect patients. This knowledge, often the domain of specialised departments of large enterprises, will now aid other teams at the University involved in biomaterials’ innovation. I have been working with Dr Jason Wong, Senior Clinical Lecturer in Plastic and Reconstructive Surgery, towards the translation of a fibrous degradable innovation for tendon repair techniques, which augments current suture repair techniques of damaged tendons by aiding cellular regrowth and guiding extracellular matrix deposition. With these innovations, we have identified that other opportunities arise to engineer new enabling surgical tools that facilitate safer and more efficient surgery. This work is now being supported by the charity, Versus Arthritis, to develop new ways to introduce biomaterials into everyday surgical use.
Outside of the University, biomaterials developed in Manchester have also been taken from lab to products that are getting close to market spun out into SMEs, with the help of commercial investment. Professors Tony Freemont and Brian Saunders together have developed a gel designed to treat chronic lower back pain resulting from degeneration of the intervertebral disc, by providing support to damaged discs. This gel is being developed by an SME called Gelemetix and is expected to enter clinical trials this year.
Outside the strict regulatory requirements of clinical trials, Professors Alberto Saiani and Aline Miller, through their company Manchester BIOGEL, are developing fully synthetic gels which are making it possible to gain a more accurate understanding of fundamental cellular function in mammals. Composed of small, simple protein components that capture individual water molecules, they give rise to a jelly like substance of varying stiffness. These fully synthetic gels, are improving the current methods of cell culture and enabling biologists to grow cells in environments that mimic the physical conditions of our bodies much more closely. When compared to standard cell culture techniques, where cells are grown on hard plastic in two dimensions, conditions they are not likely to encounter, these gels enable biologists to gain a level of understanding about cellular function, which would not be possible through standard two-dimensional culture methods. This enhanced understanding, opens up the development of new cell-based therapies and the next generation of targeted drugs.
Professors Saiani and Miller have successfully translated their discoveries into a commercial enterprise which will make their revolutionary new product available to researchers, not only in Manchester, but across the UK and internationally.
Regulation and the need for change
While there are examples of success, we are still not consistently enough translating innovative biomaterials into commercial and clinical products. A major contributor to this lack of success is a deficit of knowledge surrounding the complex regulatory environment required to ensure patient safety.
Part of the problem is a lack of understanding of the cost associated with the regulatory framework surrounding medical technologies. A new EU medical device regulation comes into effect in 2020. This aims to enhance the safety of new medical devices by requiring a Unique Device Identification System for all devices used on patients (which now includes medical software), and the approval of an expert regulatory qualified person within the organisation developing it. Practically, whilst enhancing patient safety, this regulation will make it more expensive for SMEs or academic manufacturers to produce innovative products for use within the EU. In his work on the development of Polynerve, Dr Reid also found that beyond a lack of regulatory expertise, the ability of academic institutions to engage with companies on post-manufacturing processes, such as sterilisation, packaging and distribution at grant affordable costs, has proved a barrier to successfully getting new material-based medical technologies to market. During this project it was also found that the cost of regulatory advice is high while the quality of the advice is very mixed, with no clear standards adhered to.
Given these challenges, we need to:
- Address the knowledge gap on regulations and how the process works by ensuring it’s included in PhD training programmes.
- Encourage regulators such as the Medicines and Healthcare products Regulatory Agency (MHRA), European Medicines Agency (EMA) and the Food and Drug Administration (FDA) to understand that this knowledge exchange is a two-way street, making changes where necessary to how the regulatory environment is explained and presented, ensuring there are no unintended barriers to innovation. MHRA staff have a duty to patient safety and need to facilitate promising technologies, while weeding out those which are least impactful.
- Engage the end users of the technology, both at the clinician and patient level. Clinicians need to guide the R&D process, with continual input from patients from the outset, as there are many barriers to getting a product right that cannot be addressed by focusing only from a regulatory stand point. We must always address patient and unmet clinical need, not just focus on the push of new technologies. Collectively, with some changes at both the level of the regulator and the researcher, and with input from both patients and clinicians, the biomaterials sector has a great opportunity for increased productivity, leading to more innovations and greater benefit for patients.