Update on the ethical, legal and technical challenges of translating xenotransplantation.

This manuscript reports on a landmark symposium on the ethical, legal and technical challenges of xenotransplantation in the UK. King's College London, with endorsement from the British Transplantation Society (BTS), and the European Society of Organ Transplantation (ESOT), brought together a group of experts in xenotransplantation science, ethics and law to discuss the ethical, regulatory and technical challenges surrounding translating xenotransplantation into the clinical setting. The symposium was the first of its kind in the UK for 20 years. This paper summarises the content of the expert lectures showcasing the progress which has been made in xenotransplantation including-the history of xenotransplantation, advances in gene edited animals and progress towards clinical xenotransplantation. We then set out the ethical and legal issues still to be resolved. Finally, we report the themes of the roundtable discussion highlighting areas of consensus and controversy. While the detail of the legal discussion was directed towards the UK, the principles and summary reported here are intended to be applicable to any jurisdiction seeking to implement clinical xenotransplantation.

Clinical Translation of Bio-Artificial Pancreas Therapies: Ethical, Legal and Psychosocial Interdisciplinary Considerations and Key Recommendations.

The field of regenerative medicine offers potential therapies for Type 1 Diabetes, whereby metabolically active cellular components are combined with synthetic medical devices. These therapies are sometimes referred to as "bioartificial pancreases." For these emerging and rapidly developing therapies to be clinically translated to patients, researchers must overcome not just scientific hurdles, but also navigate complex legal, ethical and psychosocial issues. In this article, we first provide an introductory overview of the key legal, ethical and psychosocial considerations identified in the existing literature and identify areas where research is currently lacking. We then highlight two principal areas of concern in which these discrete disciplines significantly overlap: 1) individual autonomy and 2) access and equality. Using the example of beta-cell provenance, we demonstrate how, by harnessing an interdisciplinary approach we can address these key areas of concern. Moreover, we provide practical recommendations to researchers, clinicians, and policymakers which will help to facilitate the clinical translation of this cutting-edge technology for Type 1 Diabetes patients. Finally, we emphasize the importance of exploring patient perspectives to ensure their responsible and acceptable translation from bench to body.

Legal and Regulatory Challenges for Emerging Regenerative Medicine Solutions for Diabetes.

Regenerative medicine solutions for type 1 diabetes are a rapidly developing field of medical technology. To date, these solutions have been principally cell-based treatments and at present, in Europe, these therapies are regulated under European Union regulations for advanced therapy medicinal products. But now, new emerging technology combining cellular therapy with medical devices is under development. The potential of this novel hybrid model to create a bioartificial pancreas to treat type 1 diabetes is tantalizing. However, incorporating medical devices creates a further layer of regulatory complexity. This article seeks to expose the complexity of this legal and regulatory landscape and demonstrate how evolving technology could challenge the entire existing legal paradigm. We start by summarizing the status of the only established cell-based therapy-transplantation. We set out the regulation of cellular therapies, their classification, and the role of statutory bodies. We examine the bottleneck of therapies moving from bench to bedside, and we consider the additional challenges of products, which use a combination of cells and medical devices. Finally, we argue that for the potential of this rapidly growing area of technology to be realized a seismic shift in how we regulate frontier cellular therapies will be required.

Inequitable Access to Transplants: Adults With Impaired Decision-Making Capacity.

Inequitable access to deceased donor organs for transplantation has received considerable scrutiny in recent years. Emerging evidence suggests patients with impaired decision-making capacity (IDC) face inequitable access to transplantation. The "Ethical and Legal Issues" working group of the European Society of Transplantation undertook an expert consensus process. Literature relating to transplantation in patients with IDC was examined and collated to investigate whether IDC is associated with inferior transplant outcomes and the legitimacy of this healthcare inequality was examined. Even though the available evidence of inferior transplant outcomes in these patients is limited, the working group concluded that access to transplantation in patients with IDC may be inequitable. Consequently, we argue that IDC should not in and of itself be considered as a barrier to either registration on the transplant waiting list or allocation of an organ. Strategies for non-discrimination should focus on ensuring eligibility is based upon sound evidence and outcomes without reference to non-medical criteria. Recommendations to support policy makers and healthcare providers to reduce unintended inequity and inadvertent discrimination are set out. We call upon transplant centres and national bodies to include data on decision-making capacity in routine reporting schedules in order to improve the evidence base upon which organ policy decisions are made going forward.