Harmonizing International Regulatory Standards for Porcine Endogenous Retrovirus (PERV) Screening in Genetically Modified Porcine Donors for First‐in‐Human Pancreatic Islet Xenotransplantation

ABSTRACT Using pig islet cells for transplants shows great promise for addressing the shortage of human donor organs in type 1 diabetes. However, it comes with unique risks from porcine endogenous retroviruses (PERV), which are found in all pig genomes and cannot be eliminated through breeding or biosecure rearing. Although there have been no reported cases of PERV transmission in early studies, the fact that PERV is a retrovirus requires strict safety measures. To minimize this risk, donor pigs are sourced from herds that are free from known pathogens and undergo rigorous screening for viruses like PERV. Regulatory bodies around the world acknowledge these concerns, with the World Health Assembly setting the “highest standards” for xenotransplant trials, the FDA requiring testing for active PERV, and the EMA and WHO guidelines recommending comprehensive screening protocols. Despite this, there are still regional differences in how long pigs are quarantined and how often they are tested, making it harder to compare data. A recent trial in South Korea, approved in 2024, is a good example of this variability, limiting the number of patients who can participate and requiring close monitoring for PERV. We suggest creating a global framework with standardized criteria for sourcing pigs and validated tests, which would allow for the mutual acceptance of safety data, improve patient protection, and speed up the translation of these treatments to clinical practice.