Regulating cell and xeno-transplants: learning from medical device oversight

The widespread availability of genetically engineered cellular products and organs for xenotransplantation could address the persistent shortage of human donor organs, but the current regulatory paradigm, which was originally designed for discrete molecular entities, is poorly suited to the paradigm of innovation in this field. The Food and Drug Administration requires sponsors to file investigational new drug applications and pursue a Biologics License Application built around a binary, one-time approval decision. This is fundamentally misaligned with cell- and xenotransplant development, which advances through cumulative incremental change in genomic edits, preservation techniques, and optimized immunosuppression. We argue that the FDA should adopt a risk-adapted framework that combines the strengths of the current biologics paradigm with lessons from medical device oversight, including early feasibility studies, evidence requirements proportionate to product risk and prior knowledge, evolving endpoints, manufacturing standards calibrated to whole organs and cellular preparations rather than mass-produced biologics, pre-negotiated change control plans, and active postmarket surveillance built on existing transplant registry infrastructure.