In this interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdocs and non-tenured researchers at University College London (UCL), Dr Mariana Diniz highlights her Cell and Gene Therapy Therapeutic Innovation Network (TIN) Pilot Data Fund awarded project, developing a cell therapy based on Natural Killer cells to treat liver cancer.  (more…)

In this interview as part of the Early Career Innovators series, recognising the amazing translational work of postdocs and non-tenured researchers at University College London (UCL), Dr Sarah Massey highlights her Devices & Diagnostics Therapeutic Innovation Network (TIN) Pilot Data Scheme awarded project involving the use of a mobile app to manage spasticity symptoms.  (more…)

In this Regenerative Medicine TIN interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdoc and non-tenured researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Hassan Rashidi highlights his Regenerative Medicine TIN Pilot Data Fund awarded project, involving human stem cell-derived 3D hepatospheres (3D Heps) for liver diseases.

What is the title of your project and what does it involve?

The project’s title is “Dissecting the cross-talk between parenchymal and non-parenchymal derivatives within human pluripotent stem cell-derived 3D hepatospheres (3D Heps) using spatial transcriptomics”.

Previously, I developed a novel xeno-free protocol to generate 3D liver organoids suitable for clinical applications. I also formulated a new culture medium to stabilise the phenotype and function of 3D Heps for over a year in culture. In this project, I will use spatial transcriptomics to dissect the crosstalk between various populations of cells within the 3D Heps.

What is the motivation behind your project/therapeutic?

Liver diseases are leading causes of morbidity and mortality worldwide, accounting for about 1–2 million deaths annually. To date, orthotopic liver transplantation is the only curative option for treatment of individuals with inherited liver disorders, end-stage liver disease and acute liver failure. However, donor organ shortage, allogeneic rejection and adverse effects associated with long-term immunosuppressant medication are major limitations.

Human pluripotent stem cells (hPSCs) represent an attractive alternative source of hepatocytes, courtesy of their unlimited self-renewal capacity and potential to differentiate to all cell types found in the human body. Recently I developed a novel platform to generate 3D liver organoids exhibiting metabolic functionality for over a year in culture. In addition, therapeutic benefit of 3D Heps was demonstrated in a mouse model of inherited liver disease.

In the current project, I will perform spatial transcriptomic to gain a better understanding of the 3D Heps. In return, transcriptomic data will be used to further improve the platform to generate hepatocytes with superior functionalities and at scale for clinical applications.

Can you highlight any challenges have you experienced as an early career researcher in the regenerative medicine/translational research space?

While being fortunate to secure funding from several charities including Rosetrees Trust, Children’s Liver Disease Foundation, Sparks and Great Ormond Street Hospital Charity, a major challenge is the limited number of funding for early career researchers since most funding calls only accept applications from established academics. This is more problematic when it comes to translational research as larger amount of funding is required. Lack of stability is another issue as an extended timeframe is expected for fruition of translational projects.

Why did you want to apply to the Regenerative Medicine TIN Pilot Data Fund?

Funding calls such as the Regenerative Medicine TIN Pilot Data Fund are the ideal source of funding for the early career researchers to generate the preliminary data required for larger grant applications such as fellowships. In addition, Blue-sky thinking is encouraged in schemes like the Regenerative Medicine TIN Pilot Data Fund, making it possible to test high-risk, high-gain projects that are typically deemed to be too adventurous.

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How did you find the process for the TIN Pilot Data Fund?

The process was straightforward as the application form was short with a quick announcement of shortlisted candidates. In addition, ACCELERATE training was offered following the announcement to prepare shortlisted candidates for the Dragon Den-style interview, which I benefited from immensely. I also participated in the ACCELERATE-CASMI Mentoring workshop, which was very helpful.

What do you hope to achieve in the 6 months duration of your project?

The data from spatial transcriptomics will provide crucial insight to further improve the 3D Heps platform. Within the project’s duration, I will complete RNA sequencing of the libraries generated from liver organoids at various stages of differentiation. I will use the preliminary data to apply for additional funding to improve the platform and to develop new technologies to benefit from tremendous potential of 3D Heps for in vitro and in vivo applications.

Dr Hassan Rashidi

Dr Hassan Rashidi is a Senior Research Associate at UCL Institute of Child Health. Dr Rashidi’s academic career has been driven by a strong interest in stem cell biology and the development of new technologies to harness the tremendous potential of human pluripotent stem cells for clinical and industrial applications.

His current focus is on development of in vitro and in vivo platforms to evaluate liver toxicity and treat liver disease, respectively.

In this Cell & Gene Therapy TIN interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdoc and non-tenured researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Giulia Massaro highlights her Repurposing TIN Pilot Data Fund awarded project, involving the use of chemokines as a novel target to improve peripheral nerve regeneration.

What is the title of your project and what does it involve?

I am currently working on a project entitled: ‘Developing a novel gene therapy approach for the treatment of obesity’. This preclinical study proposes to design and test a gene therapy product that could provide an effective treatment for a disease that is a growing burden in society. The study will use viral vectors to deliver therapeutic genes to mouse models of obesity.

What is the motivation behind your project/therapeutic?

A large medical need exists for novel obesity treatments as rates continue to increase to worldwide epidemic status, with demonstrated association to cardiovascular diseases, diabetes, cancer and other disabling disorders. In the absence of a specific pharmacological treatment, lifestyle modification and bariatric surgery are the standard of care. However, this requires full participation of the parents in the case of children, and failure to maintain weight loss after intervention is often reported.

The development of a long-lasting gene therapy treatment will not only have a positive economic impact on the health system, but also impact personal and social aspects of morbid obese patients particularly for children and teenagers.

Can you highlight any challenges have you experienced as an early career researcher in the cell and gene therapy/translational research space?

I think it is not always easy to find your voice as a young researcher in such a crowded space as within science. In particular in a cutting-edge field like gene therapy, where the race to the next ground-breaking innovation or commercialisation is relentless, ECRs are often left behind. Personally, I have been incredibly lucky to be mentored by Prof Rahim and Prof Waddington, who supported my research, gave me the opportunity to present our work at a range of international conferences and involved me in different collaborations.

Why did you want to apply to the Cell & Gene Therapy TIN Pilot Data Fund? How has it helped you?

The TIN Fund is a great opportunity for an ECR to build a preliminary data package that can be used in future applications for grants and fellowships. This first step in gaining independence is essential to grow further as a researcher in the academic environment, allowing you to strengthen the personal and professional skills necessary to build a future career as successful principal investigator within the University.

Learn more about the support provided through the TINs

How did you find the process for the TIN Pilot Data Fund? What did you learn?

It was fun! I enjoyed the ‘Dragons’ Den’ format, with both academic and industry panellists. I also attended the ACCELERATE workshop led by Simon Cane, who gave us great tips on how to present our work in the 3 minutes interview. Plus, I got the chance to meet other ECRs working in different fields and hear about their research – keep it up guys!

Future applicants will also be offered this training. Learn more – Translational training from UCL ACCELERATE

What do you hope to achieve in the 6 months duration of your project?

My plan is to develop vectors and test these in models of the disease. The COVID-19 pandemic has obviously slowed down my research, particularly affecting the availability of consumables and limiting the access to the Biological Service Unit. Nevertheless, so far I have managed to test in vitro some vector candidates, with encouraging results. I am currently producing large scale vector batches that will be used in the future in vivo studies.

Gene therapy, with its possible long-lasting effects on weight management, has to potential to offer a unified single-treatment strategy for the obese patient population, including cases due to genetic, environmental and/or behavioural factors.

About Dr Giulia Massaro

Dr Giulia Massaro is a NIHR GOSH BRC Research Fellow in Translational AAV Technology at the UCL School of Pharmacy. After her MRes in Functional Genomics at the University of Trieste and the International Centre for Genetic Engineering and Biotechnology, she joined Prof. Ahad Rahim’s Lab at UCL to complete her PhD in Gene Therapy working on rare paediatric diseases of infants. Since 2013 she has been involved in many translational gene therapy projects, collaborating with both academia and industry, focusing on rare neurological disorders with unmet medical need.

In 2020 Dr Massaro opened the GTxNeuro Viral Synthesis Facility, a state-of-the-art vector production laboratory for research-grade viral vector batches, where she provides expertise and support for new and established researchers wishing to produce customised viral vectors.

In this Repurposing TIN interview as part of the Early Career Innovators series, recognising the amazing translational work being done by postdoc and non-tenured researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Guillem Mòdol Caballero highlights his Repurposing TIN Pilot Data Fund awarded project, involving the use of chemokines as a novel target to improve peripheral nerve regeneration.

What is the title of your project and what does it involve?

The title of my project is “Chemokines as a novel target to improve peripheral nerve regeneration”. Treatments for nerve injuries have changed little over the last few decades and have significant limitations. The Lloyd lab, of which I am a part of, has previously identified Schwann cells, the major glial cells of the peripheral nervous system (PNS), as orchestrators of peripheral nerve regeneration. Recently, the Lloyd lab has identified a chemokine as a Schwann Cell chemotactic factor, secreted after nerve injury, that is likely to be important in directing the regeneration process. Nerve injuries are frequently associated with aberrant nerve regeneration that can lead to the formation of neuromas and neuropathic pain. Our goal is to determine whether using a chemokine receptor inhibitor, we can limit the Schwann Cell migration that leads to aberrant nerve regeneration and reduce the associated pain response.

What is the motivation behind your project/therapeutic?

The incidence of peripheral nerve injury is estimated to be between 13 and 23 per 100,000 people per year in developed countries. Currently, surgery is the conventional approach to repair nerve injuries but when there is a significant gap between nerve ends, an autologous nerve graft (autograft) is used. Although this is the current gold standard for treatment, autografts present several limitations and engineering strategies such as artificial nerve conduits have not been able to significantly improve the results. The unmet patient need include an often incomplete sensory and motor function recovery, neuroma formation or development of intractable neuropathic pain. Therefore, there is an urgent need to develop alternative approaches to treat peripheral nerve injuries and to prevent maladaptive regeneration, such as during tumour formation or neuroma development.

Can you highlight any challenges have you experienced as an early career researcher in the repurposing/translational research space?

I started working in the translational research space during my PhD and I would highlight that a particular challenge is the funding limitation. Even when the therapies results are promising and are likely to be taken to the clinic, this limitation could even slow down the research. Additionally as an early career researcher, another challenge I have faced is finding collaborations with pharmaceutical companies to help develop these therapies.

Why did you want to apply to the Repurposing TIN Pilot Data Fund?

Considering our last findings on the nerve regeneration process, we wanted to take our research towards the clinic. I thought that the Repurposing TIN Pilot Data Fund scheme would be the perfect fit to carry out this project since we wanted to use a marketed drug, and it would allow us to explore its potential as a treatment for nerve injuries associated with aberrant nerve regeneration.

How did you find the process for the TIN Pilot Data Fund? What did you learn?

The process for the TIN Pilot Data Fund was exciting and really fast. First, I attended the ACCELERATE training workshop and it helped me understanding not only what was required for the particular funding schemes but also the translational path. I also learnt how to be more concise with my scientific ideas when writing the application. My proposal was then shortlisted for a pitching event where we had to present our project. We received a brilliant training session that allowed me to learn how to address the pitch and connect with the audience. Overall, it was a great experience that will help me applying for future grant applications, especially for translational awards.

What do you hope to achieve in the 6 months duration of your project?

I hope to elucidate whether the treatment with the chemokine receptor inhibitor has an effect limiting the Schwann Cell migration that leads to aberrant nerve regeneration in our nerve injury model. The results obtained will allow us to improve the understanding of the nerve regeneration process. I hope this study will help us achieve more funding in the future to bring this potential therapy closer to the clinical translation. This could represent a major breakthrough in the peripheral nerve regeneration field due to the current treatment limitations.

About Dr Guillem Mòdol Caballero

Dr Guillem Mòdol Caballero is a neuroscientist that works as a Research Fellow in the Lloyd Lab, at the Laboratory for Molecular Cell Biology (LMCB) at UCL. During his PhD at Universitat Autònoma de Barcelona he evaluated the therapeutic benefits of delivering Neuregulin 1 (NRG1) to the central and the peripheral nervous systems, as a strategy to treat amyotrophic lateral sclerosis (ALS).

After finishing his doctoral studies Dr Mòdol Caballero joined the Lloyd Lab in 2019- experts in PNS biology. He is now focusing on understanding the complex multicellular interactions required for peripheral nerve regeneration and developing therapeutic modalities to take this research towards the clinic.

In this Devices & Diagnostics TIN interview as part of the Early Career Innovators series, acknowledging the amazing translational work being done by early career researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Nikolas Pontikos highlights his Devices & Diagnostics TIN (co-lead by the UCL Institute of Healthcare Engineering’s Translational & Industry Delivery Group) Pilot Data Fund awarded project, involving the use of artificial intelligence to accelerate genetic diagnosis of inherited retinal disease.

What is the title of your project and what does it involve?

The title of my project is: “Eye2Gene: Accelerating Genetic Diagnosis of Inherited Retinal Disease with AI”

Inherited retinal diseases are a leading cause of visual impairment in children and the working age population. Mutations in over 300 genes are associated with IRDs and identifying the affected gene in a patient is the first step towards diagnosis, prognosis and treatment. Currently, inherited retinal diseases are detected first by retinal imaging analysis and later confirmed by genetic analysis. Teams combining these analytical skills are scarce hence my idea is to train an AI (artificial intelligence), Eye2Gene, to achieve this in one algorithm. The training data will consist of retinal images from 4000 inherited retinal disease cases at Moorfields Hospital segmented over a 2 month period.

What is the motivation behind your project/therapeutic?

Around 30,000 individuals in the UK have an inherited retinal disease (3.5M globally). Less than 40% of patients have been diagnosed because of poor screening. A late diagnosis means less chances for treatment. Genetic diagnosis is crucial for management and treatment of patients by upcoming gene-targeted treatments. Rare disease drug development is one of the fastest growing pharma markets ($262bn by 2024). Eye2Gene will increase the rate of genetic diagnosis, allowing more to be treated sooner. There are currently no competing products for inherited retinal disease genetic diagnosis.

Why did you want to apply to the Devices & Diagnostics TIN Pilot Data Fund?

I first heard of the Translational Innovation Network Pilot Data Fund through the UCL newsletters of Personalised Medicine. I attended a few events organised by the UCL Translation Research Office and was really impressed by the guidance and support that was provided to Early Career Researchers such as translational pathways, presentation skills and grant writing workshops often led by experienced professional external consultants.

Having recently published the dataset for inherited retinal diseases from Moorfields Eye Hospital (Pontikos et al., 2020) and developed the deep-learning algorithm Eye2Gene prototype, the Pilot Data Fund seemed like the ideal kickstarter grant to launch my research project in order to build a pilot imaging dataset of segmented inherited retinal disease scans to allow for explainable AI and enhance algorithm performance.

How did you find the process for the TIN Pilot Data Fund? What did you learn?

The process was very educational. The workshops organised were of a very high standard and for the first time in my career, I received professional training in writing grants and pitching ideas. I also learnt about the translational pathway and the different stages of technology readiness. I think perhaps two workshops that stood out for me were the ones presented by Granted Ltd and by Simon Cain. As an exuberant scientist, project management (Gantt charts, KPIs, risk management etc) is always something that came as an afterthought for me, so it was quite revealing for me to see just how central it is to the grant writing process and funding success. In the future, through additional TIN opportunities, I am also very much looking forward to learning more about regulatory aspects of medical device development.

What do you hope to achieve in the 6 months duration of your project?

After 6 months I hope to have a dedicated retinal imaging annotation platform and a large manually segmented dataset of inherited retinal disease scans (>2000). This will allow Eye2Gene to offer interpretable output, highlighting to healthcare professionals exactly which parts of an image were used to derive a diagnosis. These outputs will be useful for the training of multiple AI algorithms including Eye2Gene.

Furthermore, the retinal image annotation platform that will be developed will support future image segmentation projects by facilitating collaborative editing and training of medical graders, as well as supporting medical image annotation for clinical trials. In the future, I hope to share these annotated rare disease datasets with the community and promote natural history studies and drug development. On the back of this funding from TIN, I have already submitted a project grant application to NHSX and the Wellcome Trust to support further development of the Eye2Gene software as a medical device.

What are your next steps from now?

For the Eye2Gene project I have already exported the inherited retinal disease imaging datasets and the software development of the image annotation platform has started which should be finished by end of May. After which, the annotation of images will start and I anticipate will finish in July. Further to this, the UCL Translational Office has been incredibly supportive in helping me apply for large project grants such as the Wellcome Trust Innovator Award and the NHSX AI Award. They have helped me connect with relevant individuals outside of my area of expertise, such as experienced project managers, regulatory consultants and health economists at UCL. These individuals have taken an active part in helping me write my grant applications which has been really fantastic! I will hear back from these grants in February and hope to be successful (fingers-crossed).

Whether or not I am successful with these grant applications in the short-term, I believe the whole process has greatly strengthened my grant and fellowship writing skills, especially by teaching me good project management and pitching skills.
Career wise I have also recently submitted two fellowship applications one to NIHR and one to MRC which if I am successful, will start in October 2021, giving me five years of funding. I also plan on submitting a studentship to hire a PhD student (as subsidiary supervisor).

About Dr Nikolas Pontikos

Dr Pontikos is an early career researcher funded by a short-term Moorfields Eye Charity Career Development Award. He is based at the UCL Institute of Ophthalmology and Moorfields Eye Hospital, and collaborates with the Institute of Health Informatics and the Genetics Institute. He has an MEng in computer science from UCL, a postgraduate MSci in bioinformatics from Imperial College and a PhD in genetics and machine learning from Cambridge University. He is very interested in the analysis of healthcare data to provide personalised care.

He jointly analyses genetics, medical imaging and text data to develop decision support systems for diagnosis, prognosis and treatment. His focus has mostly been on rare eye diseases but his methodology is widely applicable to rare genetic diseases. He is very interested in learning more about the regulatory aspects of developing software as a medical device.

References

Pontikos, N., et al. (2020). Genetic basis of inherited retinal disease in a molecularly characterised cohort of over 3000 families from the United Kingdom. Ophthalmology. https://doi.org/10.1016/j.ophtha.2020.04.008

In the first Small Molecules TIN interview as part of the Early Career Innovators series, acknowledging the amazing translational work being done by early career researchers within the UCL Therapeutic Innovation Networks (TINs), Clara Gathmann highlights her Small Molecules TIN Pilot Data Fund awarded project, “Screening a DNA encoded library on GEF-H1 for drugs targeting ocular diseases”.

What is the title of your project and what does it involve?

The title of my project is ‘’Screening a DNA encoded library on GEF-H1 for drugs targeting ocular diseases’’. GEF-H1 is a protein which our group has identified as a potential target for fibrotic and inflammatory ocular disorders. We have started to develop small molecules against GEF-H1, using computational and medicinal chemistry drug discovery techniques. However, our molecules are not very potent yet and we haven’t tried using high throughput screening.

DNA encoded libraries (DELs) contain billions of molecules in a single tube and can be screened on a protein within days. This technology is made possible by DNA tags attached to each molecule that encode their structures. As you may know, DNA can be amplified with PCR and sequenced. This enables a read-out of the structures of the most active molecules from picogram quantities in the tube. Hence, only one small tube is needed instead of thousands of 96-well plates. We decided to use the open source DEL library from WuXi and subject it to GEF-H1. With this, we hope to discover new molecules that bind GEF-H1 within a few weeks, giving a real kick to our drug discovery plans!

What is the motivation behind your project/therapeutic?

Preventable ocular disorders are still a major cause for vision loss. In addition to the high impact on human lives, sight loss is also a real economic issue for our societies. Even quite common ocular disorders like uveitis and retinopathies can cause vision loss if left untreated. Unfortunately, current treatments for inflammatory and fibrotic eye disorders either involve invasive surgeries or the heavy use of drugs like corticosteroids and anti-proliferative agents. These interventions are first of all not necessarily successful and have several side effects, including even vision loss!

As for many diseases, it all starts with a good drug target (in other words, a protein to inhibit). By finding potent GEF-H1 inhibitors, we hope first of all to produce useful clinical candidates that can prevent inflammatory and fibrotic damages done to the eye. But also importantly, we would show for the first time that GEF-H1 is a suitable protein to inhibit, paving the path for a new class of biological targets and providing a proof of concept for future drug discovery projects. I think this is truly motivating, to not only contribute to a cause such as a particular disorder, but also to a whole scientific field which might help completely unrelated disease classes.

Why did you want to apply to the Small Molecules TIN Pilot Data Fund?

DNA encoded libraries are an emerging technology that have gained a lot of attention lately. More and more data is published on the construction of such libraries, with some successful examples taken to clinical trials. However, the biggest libraries are often in-house libraries of pharmaceutical companies or offered by specialised companies to pharma giants. This means that drug discovery groups in academia don’t have easy access to these libraries for cost reasons, unless a collaboration is put in place. When we heard that WuXi launched this open source DNA encoded library for academia, it sounded like a huge opportunity to bring that technology into UCL and our department.

This technology can lead very quickly to positive results but would simply not have been possible to follow up on hits without the funds from the Small molecules TIN. The TIN pilot data fund seemed to be adapted due to the short-term character of the project and we hoped that such an unusual idea could awaken interest. In addition to this, applying for this kind of fund seemed like the perfect opportunity for me to learn about grant writing and how to fund research in general.

Learn more about the Therapeutic Innovation Networks and join a TIN

How did you find the process for the TIN Pilot Data Fund? What did you learn?

Overall, super exciting. While making the written application, I realised how important it is to connect our (sometimes crazy) scientific ideas to real life goals. For the first time in my life, I had to define the purpose for what I am doing in such details. In some disciplines like the ones involving clinical research, it might be easier to relate to the patients, but when you are in a lab synthesising molecules, sometimes you just loose that connection. Applying for the fund made me realise that the translational aspect of research even at its early point is really important.

Then, there was the pitching, which felt a bit like preparing for a TV show! We candidates had the chance to participate to an ACCELERATE workshop on pitching, probably the most important part of the application process. My pitch before and after that session was transformed thanks to the honest comments I received. I learnt to shift completely the initial ‘science nerdy’ focus of the talk to ‘why you should fund my project’. In summary, I learnt to tell why my project is going to make a change, and how I am going to achieve my goals in time.

What do you hope to achieve in the 6 months duration of your project?

The goal for this project is mainly to generate molecules that can be useful biological tools or clinical candidates which target GEF-H1 in ocular diseases. We want to generate accurate binding data on the hit molecules to prepare them for in vivo testing. If the screen generates potent molecules that bind GEF-H1 tightly, this will enable us to irrevocably confirm that GEF-H1 inhibition is beneficial for those diseases, fast-tracking us to clinical testing.

What are your next steps from now?

In those six months, I will first prepare materials for the screen (immobilise the proteins on beads for example), to then subject the protein to the DEL screen. After the screen is done, WuXi will process our samples, amplify the DNA tags and perform a statistical analysis on these to reveal the structures of the binders. We will then order the most potent binders for resynthesis on a milligram scale and validate them using biological assays. We typically perform biophysical assays like surface plasmon resonance (SPR) and cellular assays that model for example inflammation.

About Clara Gathmann

Clara Gathmann works between the UCL Institute of Ophthalmology and the Wolfson Institute for Biomedical Research. She is working in the groups of Prof. Balda/Matter and Dr.Chan/Prof. Selwood, focussing on the discovery of small molecules as drug candidates for common ocular diseases. She started on a Moorfields Eye Charity funded project in October 2019 involving the design, synthesis and biological assessment of molecules inhibit the GEF-H1/RhoA interaction.

Following last week’s announcement from the MHRA regarding changes to the regulation for devices to be marketed in the UK, we asked Translational Research Manager Dr Simon Eaglestone, who has represented the UCL Translational Research Office in various discussions around the new Medical Devices Regulation (MDR) for 2021, to comment on the implications this has for the devices academic community and the support available at UCL to ensure compliance and accelerate translation of medical devices to the market.

What do the new Medical Device Regulations mean for device projects in academia?
From 1 January 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) will take on the responsibilities for the UK medical devices and in vitro diagnostic medical devices market that are currently undertaken through the EU system (i.e. CE mark). The new product marking will be termed UK Conformity Assessed (UKCA), with the current Medical Devices Regulations 2002 (UK MDR 2002) continuing to have effect in Great Britain after the transition period.

CE marking will continue to be used and recognised until 30 June 2023, with medical device manufacturers in the UK having to prepare to satisfy the new EU Medical Device Regulation 2017/745 (MDR) to be fully implemented 26 May 2021. Even with this most recent announcement of how medical devices are to enter the market in Great Britain it remains clear that to market UK medical devices in the EU, manufacturers will have to satisfy the new MDR and gain CE mark certification. Whilst the MDR is written to provide clarity of regulatory requirements of economic operators and sponsors of clinical investigations, there has been confusion and uncertainty amid the academic community regarding what the MDR actually means for those investigators working in universities and partner healthcare institutes on early stage medical device projects.

What are the most significant changes in the Medical Device Regulations?
The MDR defines new obligations for manufacturing a medical device that include revised risk classification, requirements of safety and performance, clinical evidence and vigilance reporting. Arguably, the most pertinent change to affect the academic community relates to Annex I of the MDR (the General Safety and Performance requirements) and the increased needs for technical documentation and quality management systems (QMS).

Article 10 of the MDR states what manufacturers need to put in place as a minimum QMS. The QMS encompasses a defined series of processes to ensure the appropriate documentation of the entire life cycle of a medical device (including regulatory compliance, risk management, design & manufacturing, product information, usage, safety and impact). As referenced in the MDR, ISO 13485 is the recommended (but not compulsory) international standard for QMS, whereby an organization needs to demonstrate its ability to provide medical devices and related services that consistently meet customer needs and applicable regulatory requirements.

Reflecting their charitable status, universities do not generally ‘hold’ CE mark certification or place products on the market (i.e. do not act as economic operators). Successful translation of academic device projects is usually achieved by increasing asset value within the context of academic research until such time that a strategic exit is made, either by establishing a ‘spin out’ company or brokering a licensing deal with an established device manufacturer. Either of these external parties would then take on the responsibility of managing an ISO 13485-certified QMS to support their application for CE mark certification and market authority approval for the new medical device.

What should be the impending approach to quality management systems in academia?
Universities and associated healthcare institutes undertake domestic development of non-CE marked devices, or research on modified CE marked devices or those used out of intended function (i.e. ‘CE-broken’). Whilst effectively acting as the manufacturers of these early-stage devices, the implementation and maintenance of an ISO 13485-certified QMS is resource demanding and rarely undertaken by academic centres. However, there clearly is the pressing need for a change in research culture and practice that addresses the need for appropriate technical documentation in the early life cycle of medical devices.

The incoming MDR has prompted health institutions to migrate their existing QMS infrastructure from ISO 9001- to ISO 13485-certification. Health institution exemption (HIE) from MDR may be secured for manufacturing, modifying and using custom made devices ‘on a non-industrial scale’, within the same health institution (i.e. legal entity). However this ‘in house manufacturing’ demands appropriate QMS and documentation to ensure such products meet the relevant General Safety and Performance Requirements. Significantly, health institutions will be compelled to apply for exemption under the new MDR, thereby closing a potentially overused pathway for academic medical device research via partner health institutions.

Making academic medical device translational more successful
To promote medical device development and successful translation to market with enhanced patient benefit, there is growing support in the academic community for initiatives that will improve knowledge of regulatory requirements and present investigators with both pragmatic and the least onerous solutions to satisfy regulatory compliance in early-stage device projects and facilitate commercialisation.

Whilst the academic exit strategy described earlier negates the need for implementing a fully certified QMS, there is a compelling incentive for device researchers within universities to commit time, effort and resources to implementing a proportionate QMS for each medical device project. The ability to attract external investment to support the progression of a university’s domestic device to market is greatly enhanced by the existence of a balanced QMS and documentation developed throughout the entire project lifetime toward ‘CE-readiness’.

The future for UCL
Just as the Clinical Trials Directive of 2001 enhanced the conduct of clinical trials on medicinal products for market within the European Union, the incoming MDR has presented a motivation for enhancement to the culture and way in which UCL researchers undertake and ultimately improve the likelihood of successful translation of university medical device development.

Throughout 2020, UCL’s Translational Research Office (TRO), Institute of Healthcare Engineering (IHE) and Joint Research Office (JRO) have been working closely to develop standardised tools that will support investigators in keeping and updating device project records.

Over the coming months, the Devices & Diagnostics Therapeutic Innovation Network (D&D TIN) shall be hosting community events to enable investigators to access local resources (e.g. QMS & document templates) and implement solutions for centralised management of a university department/Sponsor device project portfolio. Whilst non-compliance with the QMS would not preclude their ongoing research activity, it would likely hamper investigators ability to progress at a later stage (e.g. refusal of Sponsorship for clinical investigation).

Watch this space for the Devices & Diagnostics TIN QMS workshop, scheduled to take place before the end of the year (date TBC). In the meantime, become part of the Devices & Diagnostics community at UCL by joining the Therapeutic Innovation Networks: a platform for UCL, partner Biomedical Research Centres (BRCs) and industry partners to connect, collaborate and share best practices to translate at pace. Any workshops relating to the new MDR will be communicated to the Devices & Diagnostics TIN community through Teams and via email before being announced more publicly.

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What is the Devices & Diagnostics Therapeutic Innovation Network (TIN)?
The Devices & Diagnostics TIN is one of 6 UCL Therapeutic Innovation Networks hosted by the UCL Translational Research Office, positioned around a specific modality rather than subject area, to encourage the formation of strategic multidisciplinary alliances to close the academic/clinical/patient/industry interface.

Additionally, the TINs aim to widen participation and remove barriers to translation by providing education and funding opportunities to basic and translational researchers from Early Career Researchers to PIs.

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