The Challenges of Regulation – Why Is FMT So Difficult to Classify?
FMT is at once a drug, a tissue, and a procedure; this chapter explains why a living microbial ecosystem resists every existing legal box.
A procedure that fits into no single box
The fundamental regulatory challenge of FMT stems from the fact that the procedure does not fit neatly into any single traditional legal category [311]. Drug? Tissue? Cell transplant? Medical procedure? The answer to each is simultaneously "yes and no" – and this categorical uncertainty has direct consequences for the content and stringency of regulation.
When the first cars appeared at the end of the 19th century, the British legislature responded with the "Red Flag Act": every motor vehicle had to travel at no more than 6 km/h, and a person had to walk ahead with a red flag to warn horses and pedestrians. The law attempted to apply existing categories (pedestrian traffic, horse-drawn carriages) to the new technology – and nearly strangled the British automobile industry, while the automobile developed freely on the continent. The same risk applies to FMT regulation: forcing existing legal categories as a straitjacket onto a fundamentally new type of medical intervention not only hinders the development of the procedure, but also restricts patient access.
The main categorisation dilemmas
- Drug vs. tissue: If FMT is regulated as a drug, clinical trials, manufacturing licences and pharmacovigilance systems are required [311], [312] – involving enormous costs and time commitments, potentially unachievable for small-volume, non-profit donor banks. If regulated as a tissue, tissue banks can operate under a lighter regulatory burden, but quality and safety requirements may also be weaker.
- Industrial vs. hospital preparation: Commercial FMT products (e.g. Rebyota, Vowst) require industrial GMP standards. Hospital "bedside" FMT – where donor stool is prepared directly for a specific patient – falls under different regulatory logic, but the boundary between the two is not always clear.
- The paradox of regulating a living biological system: Conventional drugs have chemically defined, reproducible active substances [311], [263]. The active substance of FMT is a complex, living microbial ecosystem that can vary dramatically between donors, sampling timepoints, and processing methods. How can reproducibility and stability requirements be defined for such a material?
- Consent and anonymity: The handling of donors' personal data, informing recipients about the donor's health status, and long-term follow-up obligations raise data protection and bioethical questions for which existing legal frameworks provide no unambiguous answers.
- Cross-border application: Patients travel to other countries for FMT where regulation is more permissive [312], [263]. Donor banks ship preparations across national borders. This raises the question: which country's regulation applies, and how can it be enforced?
References
[263] EMA/HMA. Faecal Microbiota Transplantation – EU-IN Horizon Scanning Report. EMA/204935/2022/Rev. 1 (updated May 2025). 2022. Link
The 2022 (updated May 2025) EMA/HMA 'Faecal Microbiota Transplantation – EU-IN Horizon Scanning Report' (EMA/204935/2022/Rev. 1) is the official European Medicines Agency horizon-scanning analysis of FMT regulation. It maps the heterogeneous EU regulatory landscape (tissue, drug, blood-component or hybrid frameworks across member states), reviews clinical evidence by indication (CDI, IBD, hepatic encephalopathy, decolonisation of MDROs), and identifies harmonisation priorities. The report informs the EU SoHO Regulation 2024/1938 negotiations and proposes a coordinated approach to donor screening, stool-bank licensing, traceability, pharmacovigilance and clinical-trial registries. It is a key policy reference for EU FMT governance.
[311] Keller JJ, Ooijevaar RE, Hvas CL et al. A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group. United European Gastroenterol J. 2021. Link
This European consensus document provides detailed guidance on all processes related to collection, handling and clinical application of human donor stool for faecal microbiota transplantation (FMT). Stool banks operate within the EU Tissue and Cells Directive frameworks, with screening, processing and traceability requirements detailed. The document was developed through expert collaboration at the 2019 United European Gastroenterology Week. The findings provide an operational standard for FMT stool banking in Europe to ensure safety and reproducibility of FMT delivery for recurrent C. difficile infection and other indications.
[312] Ianiro G, Mullish BH, Kelly CR et al. Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic. Gut. 2020. Link
This position paper provides global FMT-community guidance for FMT centres and stool banks during the COVID-19 pandemic. Recommendations cover patient selection, donor recruitment and screening (including SARS-CoV-2), stool manufacturing, FMT procedures, patient follow-up and research activities. The aim is to maintain reliable patient access to FMT for recurrent C. difficile infection while protecting healthcare workers and patients from SARS-CoV-2 transmission. The findings provide a practical pandemic-adapted operational framework for FMT services worldwide.