Biomodifying technologies and experimental space: organisational and regulatory implications for the translation and valuation of health research.

Lead Research Organisation: University of Oxford
Department Name: Law Faculty

Abstract

Developments in biomedical innovation today can be seen in areas such as robotics, digital systems or new imaging techniques - and increasingly in areas marked by highly sophisticated forms of medical biology and biotechnology that involve altering 'natural' biological processes. Three key developments form the focus for this project: the arrival of 'gene-editing' whose goal is to understand and remove disease-related mutations, the creation of induced pluripotent stem cells that can be controlled to create different types of tissue for cell therapy, and the emergence of 3D printing of biological material which aims to create novel structures for bodily repair and renewal.

These developments can all be described as 'biomodifying technologies', that is, those that modify living biological tissue in novel and increasingly patient-orientated and customised ways. These are not simply important in a biomedical sense but also in the ways in which they are reshaping the landscape of biomedical innovation in the 21st century. Not only do these technologies challenge existing governance frameworks in terms of standards for safety, quality control, and traceability of biological materials, equally and perhaps more importantly, they raise new questions for health systems and social science inasmuch as these are 'gateway' technologies with wide-ranging applications, significant commercial engagement and high levels of transferability, which open up far-reaching possibilities. We need to understand and anticipate such developments if we are to build an informed and constructively critical social science of biomedical innovation today. More broadly, this contributes towards the ESRC's core priority and delivery plan aim of supporting research that can promote economic growth and development, and to do so in a way that is based on robust, engaged social science that maps and analyses the implications of innovation.

The project will contribute towards STS theory through the development of a conceptual framework for the analysis of 'experimental space', a framework built through the analysis of the spatial characteristics of the science of biomodifying technologies, the processes of valuation at work in these spaces, and the regulatory and governance landscape of the field. The first element focuses on the sites at which biomodifying technologies are developed, the geographical networks through which they are mobilised, and, the knowledge-based terrain they define, through which biomedical scientists build new models, standards, trials and clinical applications. The second element draws on recent social science work on the meaning of value - sometimes called 'valuation studies'. Here we are interested in discovering how values and benefits are defined, by whom, and according to what criteria. Our third element draws on social science work on regulation and governance, in particular, work that explores the tensions between regulation, law, and new biologies. Together these approaches help us to build and analyse datasets that will allow us to understand the current and future impact of the three technologies in the hospital, the clinic, the firm and the wider implications they will have for the health system.

The project will use a mixed methods approach for UK fieldwork combining documentary analysis of various literatures, including the academic and grey literatures, with qualitative semi-structured interviews with a range of key stakeholders in each of the fields being studied. These include scientists working in academic laboratories, representatives of SMEs, patient groups, research agencies, regulators, and senior staff in important service organisations (e.g. biobanks). Secondary data from other European, US and East Asian sources will also be secured.The project will result in data, academic papers and policy reports that will offer the first comprehensive social science analysis of these major developments in biomedicine.

Planned Impact

The project's research findings will benefit the following groups: innovators and industry, policymakers and regulators, healthcare professionals and managers, patients and publics. Details of each group and how they will benefit are provided below:

Impact on innovators and industry - beneficiaries include non-academic researchers, technology developers and firms (Small / Medium Enterprises and large companies) with an interest in developing, translating and commercialising biomodifying technologies and products and services derived from them. Research findings will have impact by i) informing early stage development of new biomodifying technologies by providing insight into the needs and valuation practices of a variety of stakeholders including patients, regulators, and health service professionals ii) helping to shape viable business models for deploying biomodifying products in the healthcare marketplace. The mapping of the experimental and regulatory landscape will also provide valuable guidance on the legal and ethical requirements and responsibilities of service providers. Several project members are members of the UK Association for Studies in Innovation Science and Technology (AsSIST-UK) which has been set up with the goal of supporting social sciences engagement with science and innovation, civil society, government, and industry within the UK and globally, and is particularly well-suited to facilitating impact of the kind envisioned for this project.

Impact on policy and regulation - beneficiaries will include agencies and regulatory actors responsible for the governance of biomodifying technologies and policy makers promoting the social and economic benefits of innovative medical technologies. Research findings will have an impact by i) providing an evidence-base on the social, regulatory and organisational implications of current research trajectories and translational pathways for biomodifying technologies, ii) identifying what kinds of evidence are being required and what types of valuation practices are applicable for different applications of biomodifying technologies, and iii) highlighting significant dimensions of the experimental space for the three cases studies to inform policy and regulatory decision-making for emerging products and services.

Impact on healthcare professionals and managers - Healthcare professionals and NHS managers will benefit from having a robust empirically informed overview of the experimental space of biomodifying technologies that will allow them to identify prospective applications and the translational and regulatory landscape in which these research trajectories are embedded. This is pertinent for the future uptake of innovative biomodifying technology products and services and where healthcare professionals and managers will play a key role in translating biomodifying technologies from the experimental space to clinical adoption. Healthcare professionals and NHS managers will also benefit from the inclusion of NHS representatives in the expert workshops and data generation phases of the project.

Impact on patients and publics - beneficiaries include patients, charities and patient interest organisations, and various publics. Patients and patient organisations will benefit from the opportunity to have their needs and perspectives on the value of different biomodifying technologies, their associated translational pathways, and the types of evidence and valuation at stake solicited as part of the project's empirical data collection and used to inform the project outputs and findings. We have excellent links with the MHRA's Patient Forum which will provide an important vehicle for this. There will also be opportunities to participate in expert workshops and take part in upstream engagement with other key stakeholder groups. Findings will also have an impact by informing and encouraging participation in public debates on innovative biomodifying technologies.
 
Description There are important differences in the 'experimental space' for each of our case study technologies. Induced pluripotent stem cells fit most readily into existing regulatory categories designed for cell-based therapies, and they are often seen as a replacement for treatments previously being developed with human embryonic stem cells. Gene editing is also commonly regarded as falling within the EU Advanced Therapy Medicinal Products regulations, but there are questions about how well tools such as CRISPR-Cas9 are actually captured by existing legislation designed to regulate recombinant DNA technology. 3D printing of cells and tissues is the most 'disruptive' of the three technologies in regulatory terms. The potential for localised customisation of bioprinted implants for individual patients raises questions of manufacturing liability that are rarely seen with existing cell therapies or transplants and it may be more appropriate to look to case law around prosthetics and non-biological implants to identify the relevant legal precedents.
The translation of each of these technologies is significantly shaped by existing structures. These structures can be intellectual; such an existing commitment to using cultured human cells to replace damaged tissues or replacing deleterious genes with non-pathogenic variants using gene-altering technology, but they can also be material and organisational: applying any of these technologies to treat a particular disease, or stratified patient population, is much more likely to be seen as achievable if it builds on existing professional skill sets, manufacturing and delivery capacities, reimbursement mechanisms, and facilities, than if it requires new or radically revised capabilities. In this regard the UK has already made considerable investment in translational infrastructure for cell and gene therapies, but this is less attuned to the needs of the younger 3D bioprinting sector.
Translation, and commercialisation of each of these technologies is at different stages of maturity, but they all face socio-technical challenges in making treatment deliverable. As an example, setting standards such as the acceptable parameters for critical quality attributes of a cell or gene based medicinal product requires technical expertise, but it also requires negotiation between academic and commercial developers of the therapy and regulators. It is both social and technical, as it requires coming to agreements about what can be measured and known, what it is important to measure and know, and what degrees of risk and of uncertainty are tolerable, depending on the severity of the disease being treated, the availability of alternative interventions, and the degree of anticipated patient benefit. The UK has historically been a leader in developing models for regulating socially and technically complex technologies such as IVF, and advanced therapies presents an opportunity to extend this exercise of 'soft power' by developing and promoting internationally accepted standards of practice. The international scope of technology development and scientific research means that standard setting is only likely to gain traction if undertaken in collaboration with strategic international partners.
Exploitation Route As these interim findings are supplemented by synthesis of our remaining interview data, scientometric data and regulatory analysis we will be able to provide a nuanced account of the advantages and limitations of the UK landscape for developing Biomodifying technologies to policy makers, regulatory, academic and companies working in this space, and to identify areas for strategic attention. in addition our future finding will include the perspectives of patient groups and charities on the value of cell and gene therapies and bioprinted implants which will provide a basis for (more) dialogue between scientific and technical experts on the one hand and the end users of Biomodifying technologies, the patients, on the other.
Sectors Government, Democracy and Justice,Pharmaceuticals and Medical Biotechnology

 
Description The 'Biomodifying Technologies' project currently in its second year. The research team have made good progress with the work of mapping the current UK landscape for each of the case study technologies: gene editing, induced pluripotent stem cells ('iPS cells') and 3D printing of living biomaterials. Through this, especially the interview work we have built up a good network of contacts and awareness of the major institutional actors in each field. This will allow us to feedback our end of project results directly to end users in the form of policy briefings and short reports. Team members have participated in several engagement and policy making events. Professor Andrew Webster and Dr Michael Morrison participated in a two-day workshop on the governance of gene editing for human clinical applications organised by the Working Party on Biotechnology, Nanotechnology and Converging Technologies (BNCT) of the Organisation for Economic Co-operation and Development (OECD) in conjunction with the German Federal Ministry of Education and Research (BMBF) and the Korean legislation Research Institute (KLRI). Professor Webster contributed text to the final text of the policy report produced by the workshop while Dr Morrison provided a recently published paper on regulation of clinical gene-and-cell therapies, on which he was a co-author, to the OECD working group, which was also cited in the final report. Dr Phoebe Li has been interviewed for Al Jazerra on the legal and ethical implications of 3d bioprinting and took part in a scenario workshop on additive biomanufacturing and 3D printing for human application organised by the Rathenau Institute (Netherlands) and hosted at the European Parliament. Professor Webster also took part in an expert roundtable meeting on gene editing organized by the UK department for Business, Energy and Industrial Strategy (BEIS). In addition, project team members have been in contact with researchers dealing with regulation and innovation of one or more of our case study technologies in a variety of countries (Australia, Japan, Portugal) with a view to establishing channels for international dissemination of future project findings and potential avenues for comparative analysis of national strategies. We have established a project website and social media (Twitter) presence to disseminate general information about the project to a variety of audiences. These facilities can also act as a channel for disseminating specific project findings going forward. The majority of our impact will come at the end of the project as we disseminate our key findings from three years of cumulative work and disseminate it to local and international audiences.
First Year Of Impact 2017
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Policy & public services

 
Description Dr Phoebe Li acted as a pre-publication peer review of UK IPO report on 3D printing
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
URL https://www.gov.uk/government/publications/3d-printing-and-intellectual-property-futures
 
Description Participation in OECD Expert Workshop Gene editing for advanced therapies: governance, policy and society
Geographic Reach Europe 
Policy Influence Type Participation in a national consultation
URL https://www.innovationpolicyplatform.org/system/files/imce/OECD_Gene%20editing%20expert%20meeting_dr...
 
Description Prof Webster invited to participate in BEIS roundtable on genome editing
Geographic Reach National 
Policy Influence Type Participation in a national consultation
URL https://www.york.ac.uk/satsu/news-events/news/genomeeditingresearchlandscape/
 
Description Responsive mode grant
Amount £340,000 (GBP)
Funding ID RPG-2017-330 
Organisation The Leverhulme Trust 
Sector Academic/University
Country United Kingdom
Start 09/2018 
End 08/2021
 
Description Biomodifying Technologies project website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Biomodifying technologies project website provides a description of the project, what we hope to achieve and who this research is intended to benefit. It provides an online point of reference for anyone interested in learning more about our work or who is considering responding to an invitation to be interviewed as part of our fieldwork. The website also provides information about the project team members, has a 'contact' facility and a page where we can disseminate news and activities from the project.
Year(s) Of Engagement Activity 2017,2018
URL https://www.biomodtech.com/
 
Description Biomodifying technologies Twitter account 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Biomodifying technologies Twitter account is run by Dr Bartlett at the University of York. It serves multiple functions including raising awareness of the project among relevant stakeholder communities, collecting up-to-date information on academic, commercial, regulatory and policy developments in the fields of genome editing, induced pluripotent stem cells, and 3D bioprinting, and serves as one site where actors from each of these research areas who are active in the UK can be identified. The account will also be used to promote project events and outputs (e.g. policy briefs) as these become available during the course of our work.
Year(s) Of Engagement Activity 2018
URL https://twitter.com/BioModTech
 
Description Dr Phoebe Li interviewed by Al Jazeera TV on ehtical and legal challenges of 3D bioprinting 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Dr Phoebe Li (Sussex) was interviewed by Al Jazeera's English language channel for a news item about Russian plants to put a 3D bioprinter in space. Dr Li was asked comment on the legal and regulatory implications of bioprinting and of distributed manufacturing of medical devices and implants being carried out in extra-terrestrial- domains- that is space shuttles and orbiting platforms. Dr Li's segment of the item begins at 2m 10s into the YouTube clip. As of March 2019 the clip had over 3000 views in addition to the audience for the original audience.
Year(s) Of Engagement Activity 2018
URL https://www.youtube.com/watch?v=-VxFaB8yR6o
 
Description IngentaConnect profile piece of the project and its aims 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact The Impact publication is promoted to 35,000 individuals worldwide within academia, government, research centres, funding agencies and research councils. This specific issue is 80 pages in length, with other articles from researchers working in Social Sciences from across the world featuring alongside the project-specific article.
There are over 24,000 Universities, institutes and companies in Europe and 21,000 in the USA, from both the public and private sector, who are registered for their staff to access content from this resource. The article will be free to read and download, open access, on IngentaConnect and as a result of this, will be available through Google Scholar, EBSCO, Primo Central and World Cat Discovery, while also receiving a Crossref DOI and be deposited in Portico - one of the leading deep repositories.
Year(s) Of Engagement Activity 2019
URL https://www.ingentaconnect.com/content/sil/impact/2019/00002019/00000001/art00021
 
Description Science and Technology Options Assessment Panel project: additive biomanufacturing 3D printing for medical recovery and human enhancement - Scenario workshop at European Parliament 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Dr Phoebe Li attended and participated in a scenario workshop at the European parliament organised by the Rathenau Institute (NL) as part of the STOA (The European Parliament's Science and Technology Options Assessment Panel) project: on "Additive bio-manufacturing, 3D printing for medical recovery and human enhancement". the workshop was held in September 2017. Workshop participants were presented with four scenarios of how 3D bio-printing and medical bio-manufacturing might operate in 2035 and asked to assess and evaluate these scenarios and provide constructive feedback on each. The aim of the workshop is to support the Members of the European Parliament and their Committee to understand potential trends in bio-printing and additive manufacturing for medical purposes in order to anticipate and plan for their policy impact.
Year(s) Of Engagement Activity 2017