Biovigilance in Faecal Microbiota Transplantation: 7‐Year Cohort Study and Framework for Microbiological Assessments of Infectious Adverse Events

BACKGROUND AND AIMS: Faecal microbiota transplantation (FMT) is increasingly used. However, no systematic approach exists to assess infectious risks after FMT, leading to underreporting. We evaluated infectious complications at the Netherlands Donor Feces Bank (NDFB) and proposed a structured biovigilance approach aligned with the EU Regulation on Substances of Human Origin (SoHO). METHODS: We conducted a prospective observational cohort study of all patients receiving frozen donor faecal suspensions from the NDFB (May 2016-December 2023) for recurrent Clostridioides difficile infection (rCDI) or via an extended access programme (EAP) for non-CDI indications. (Serious) adverse events ((S)AEs) were reported by physicians and recorded at 3 weeks, 3 months, and 6 months. Serious adverse reactions (SARs) were defined as SAEs probably or definitely related to FMT. RESULTS: We included 290 rCDI patients (322 FMTs) and 35 EAP patients (75 FMTs). FMT efficacy was favourable overall: 92% of rCDI patients remained free of rCDI within 8 weeks, and 49% of EAP patients achieved at least a partial response. Sixty-one per cent of rCDI patients and 34% of EAP patients had mild gastrointestinal AEs. AE incidences were comparable across groups (rCDI: 5.1 vs. EAP: 4.4 per 100 patient-weeks). SAEs were more frequent in EAP patients (0.66 vs. 0.28 per patient), reflecting higher immunosuppression and comorbidity. FMT-attributable SARs occurred after 6 of 322 FMTs (1.9%) in the rCDI group and after 3 of 75 FMTs (4.0%) in the EAP group. Two donor-derived Escherichia coli infections in EAP patients with predisposing conditions were confirmed, consistent with early donor-strain colonisation rather than a direct FMT effect. Most SAEs were unrelated. CONCLUSIONS: In this 7-year cohort, donor-derived infections were rare but present, particularly in non-CDI patients with substantial comorbidity, whereas overall safety remained favourable. A SoHO-compliant biovigilance protocol incorporating microbiological investigation and donor/sample traceability is essential for the safe clinical use of FMT and faecal microbiota products.