Xenotransplantation of decellularized pig heart valves—Regulatory aspects in Europe

Abstract

Background The lack of human donors for allotransplantation forces the development of other strategies to circumvent the existing organ shortage documented on the waiting lists. Here, xenotransplantation offers a suitable option since the genetic modification of animals has become an established method that allows the generation of animals as donors of cells, tissues, and organs with reduced antigenicity. Methods Focus is given on the generation of decellularized matrix scaffolds, for example, for valve transplantation and/or repair, that have the potential being fully assimilated by the recipient as they are no longer a mechanical implant with risk of calcification and related failure. Results This new class of products is transplants that will be regulated either as medical devices or as cell‐based medicinal products, that is, advanced therapy medicinal products, according to the regulations in the European Union. Conclusions In this review, we compile relevant regulatory aspects and point out the possibilities of how these products for human use may be regulated in the future.

Pathways to Clinical Cardiac Xenotransplantation

“…The important issue of regulation is underlined by the fact that all 3 major authorities involved, the World Health Organization, 49,143 the US Food and Drug Administration, 144 and the European Medicines Agency, recently published updates of their respective previous guidelines (reviewed in Schuurman and Hoogendoorn 142 ); the International Xenotransplantation Association dedicated its 2020 May/ June journal issue to regulatory aspects. 142,143,[145][146][147][148][149][150] Both donor animals and recipients need tight and transparent tracking; controlled long-term archiving (biobanking) of donor and recipient samples is undisputed. Only experienced groups will be allowed to proceed.…”

Organ transplants of the future: planning for innovations including xenotransplantation

“…Given the complexity and potential risks of participation in clinical trials, patients and advocates should be involved throughout the planning of each study. The processes of defining and obtaining informed consent should be determined in clinical trial protocols, but before consent can be 'informed', public-and patient-focused programmes should build awareness and knowledge of solid organ xenotransplantation across the community [77,83,[86][87][88]96].…”

“…However, different regions use different terminology. For example, the term 'ATMP' is only used in Europe[77]. In the United States, a xenotransplantation product is considered a biological product, but a xenograft (e.g.…”

“…a xenogeneic heart valve) is described as an acellular or decellularized product, regardless of process. In contrast, the equivalent of a xenograft in Europe is considered a medical device and subsequently an ATMP, according to the regulations[77,78]. Clinical development planning for xenotransplantation will undoubtedly have such publications at its foundation, although new guidance could aim for global harmonization of the terminology, particularly with respect to the definition of the product.…”

Xenotransplantation literature update, May/June2020

“…In this new approach pig organs are harvested from either wild‐type or genetic modified animals, then the organs are decellularized. Once the organ is decellularized, the organ will be used as a scaffold for autologous cells typically done in vitro 33 . These pig‐derived products will either be regulated as medicinal products or medical devices.…”