LAUSR

The first successful kidney transplants using human donors date from the 1960s and the first heart transplant was conducted in 1963. Clinical transplantation became thereafter a well-accepted medical procedure, with a boost after the introduction of proper immunosuppressive medicines such as cyclosporine in the 1980s. It was quickly realized that there was a shortage in availability of human organ donors, which logically led to initiatives to use organs from animals. Pioneering experiments using a kidney1-3 from non-human primates were already performed in the 1960s, and this was followed by first heart transplants4,5 including the well-known Loma Linda case in 1984.6 Survival times were rather poor; however, survival up to 9 months was documented for a chimpanzee kidney transplant7 and 70 days for a baboon liver transplant.8 It was soon realized that non-human primates are for various reasons not suitable as donor, and the interest shifted to the swine species, with major projects starting in the 1990s. Safety, in particular the risk for transfer of infectious agents, became then also an issue. Regulatory agencies became interested by the end of the 1990s and with a main focus on infectious risks; among the first documents issued were the 2001 US Public Health Service “Guidelines on infectious disease issues in xenotransplantation”9 together with the 2001 WHO “Guidance on xenogeneic Infection/disease surveillance and response”.10 The first clinical trial under regulatory oversight was the trial with encapsulated neonatal porcine islets, sponsored by Living Cell Technologies in New Zealand. The long period in achieving regulatory approval is well described.11 It is generally assumed that clinical testing of xenotransplantation products, that is, cells, tissues, or organs, will need, a.o., data on survival and function in vivo in relevant animal models, which was more easily achieved for xenogeneic cell therapy products than for xenogeneic organs. Such data are now becoming available in research studies of the last years, together with increased insight in infectious risk and other safety aspects. It is therefore logical that there is more communication between regulatory agencies and institutions involved in research and development, illustrated by, for example, a joint symposium organized by the US Food and Drug Administration (FDA) and the International Xenotransplantation Association (IXA), in association with the IXA congress in 2017.12 At the last IXA Congress in Munich, October 2019, a special half-day session was held on regulatory aspects, with presentations by representatives from regulatory agencies and the science and development field. These presentations were quite informative resulting in a productive discussion at the end. This session was therefore taken as the basis of this theme issue in Xenotransplantation on regulatory aspects. Evidently, regulatory oversight cannot be summarized in one issue of the journal, so the guest editors rather focused on specific topics of recent interest. The theme issue starts with a summary written by Wayne Hawthorne of the partnership between the World Health Organization (WHO), The Transplantation Society, and IXA: This partnership has shown its importance, a.o., in organizing Global Consultation Meetings in which recommendations for clinical trials and a document on infectious risk were discussed. Noteworthy, the WHO has been involved from the early days of regulatory oversight of xenotransplantation, and this partnership has been very productive, for instance in the design of an International Human Xenotransplantation Inventory.13 Internationally, xenotransplantation has made major progress in China and South Korea, and regulatory oversight has received attention in a number of publications in this journal during the last years. There have been major developments in the structure and operations of regulatory oversight during the last years, and this