FDA xenotransplant guidance is 20+ years old and outdated

The FDA's guidance documents governing xenotransplantation were primarily written in the early 2000s, before CRISPR gene editing existed, before any pig organ had been transplanted into a living human, and before the current wave of multi-gene-edited donor pigs. These documents do not address modern biosecurity concerns specific to gene-edited animals, do not provide clear frameworks for how many gene edits constitute a new biological product requiring separate approval, and do not define adequate surveillance protocols for novel zoonotic risks from 69-gene-edited pigs. As xenotransplantation rapidly enters formal clinical trials (FDA approved two pig kidney trials in February 2025), the regulatory framework has not kept pace. Clinicians and companies like eGenesis and United Therapeutics face uncertainty about what standards their donor animals, facilities, and monitoring protocols must meet. The consequence is that each clinical program negotiates its own ad-hoc regulatory pathway with the FDA, creating inconsistency and delays. This persists because the FDA has limited staffing and precedent for regulating living animal-derived biological products, and xenotransplantation falls awkwardly between the FDA's Center for Biologics (CBER) and its veterinary oversight, with no dedicated regulatory division.