The regulatory frameworks applicable to microbiome-based products depend on their intended use, meaning these products may fall under a variety of frameworks, including medicinal products, food supplements, food products, foods for special medical purposes (FSMPs). This broad range of regulatory statuses is associated with distinct requirements regarding safety, quality, and market access pathways.
A significant shift in the European regulatory landscape is currently underway with the new SoHO Regulation (Substances of Human Origin) that came into force in August 2024 and will become fully applicable in August 2027 following a three-year transition period. This framework explicitly brings human microbiome samples within its scope, subjecting them to harmonised requirements for quality, safety, effectiveness and traceability under the supervision of national competent authorities. While separate from the medicinal product framework overseen by the European Medicines Agency (EMA), this development introduces a new regulatory framework for certain microbiome-based interventions such as microbiota transplantation, including faecal microbiota transplantation (FMT) and vaginal microbiota transplantation (VMT).
Further clarity is expected with the forthcoming EU pharmaceutical legislation package, anticipated fall 2026, which should help define how the SoHO framework will interact with the medicinal product regulatory pathway.
Currently, the Pharmabiotic Research Institute (PRI) plays a key role as a bridge between academic institutions, industry and regulators. The institute represents the microbiome field by helping ensure that microbiome-specific characteristics and technical considerations are appropriately addressed in the development of regulatory frameworks and guidelines shaping microbiome innovation. The PRI team recently published a review on European regulatory developments, highlighting the broad spectrum of microbiome-based therapies and providing an overview of the current framework.
The GMFH editing team connected with Dr. Céline Druart, executive director of the PRI, to explore how the field is navigating this evolving regulatory landscape, the challenges it presents, and the opportunities it opens for innovation in microbiome-based therapies.
How would you describe the current regulatory landscape in the European Union for microbiome-based therapies? Where do you see the biggest gaps or inconsistencies at the moment?
“The objective of the new SoHO Regulation is to increase the level of harmonisation but also the safety, quality and effectiveness of SoHO, including microbiome transplantation.”
“At the moment, microbiome-based therapies are either regulated at the national level for the “microbiota transplantation”, such as FMT and VMT, or either as medicinal products for LBPs (Live Biotherapeutic Product) or any other microbiome-based medicinal products. However, as highlighted by a Horizon Scanning Report published by the Heads of Medicine Agencies, there is currently a lack of harmonisation in how the microbiota transplantation is regulated as this procedure is regulated as medicinal products in some countries, as a transplant in other countries and finally on a case-by-case basis in other countries. This represents an issue for patients’ access to treatment but also for exchanging FMT preparation from one country to another, and a lack of harmonisation into the follow-up of microbiome donor and microbiota transplantation recipient. The objective of the new SoHO Regulation is to increase the level of harmonisation but also the safety, quality and effectiveness of SoHO, including microbiome transplantation.”
Could you elaborate on the key challenges that donor-derived complexity introduces for faecal microbiota transfer, particularly from a regulatory and standardization perspective?
“Right now, the “donor complexity” is not an issue, as the only approved indication for FMT is recurrent Clostridioides difficile infection (rCDI) and there is data showing that the composition of the microbiome is not so important in this indication. The key aspect is transferring a microbiome free of pathogens. This ecosystem will populate the gut of the recipient and will avoid the colonization by C. difficile. However, for other indications that are still under development, the composition of the donor microbiome can be important and then there is the challenge of analysing this composition, together with the broader challenge in the field of the lack of consensus on what constitutes a «healthy microbiome».”
How would you assess the progress made so far in implementing microbiome-related regulatory frameworks across Europe?
“It’s very important that actors concerned with these products submit comments as these comments will serve as a basis for the development of future guidance.”
“The progress in regulatory is always slower than the scientific progress, that’s inherent to regulatory developments, as the regulators cannot regulate something that does not exist. In EU, the first regulatory development regarding microbiome-based therapies was the publication of the European Pharmacopoeia (Ph. Eur.) monograph on LBP. This document addresses the quality requirement for LBPs.
Right now, we can see that LBP but also other microbiome-based therapies are clearly recognized by the regulatory authorities, and we can see major regulatory developments such as the new SoHO regulation but also the concept paper* recently published by the EMA on “Non-clinical development and evaluation of microbiome-based medicinal products”. This document is the first step towards the development of guidance supporting the non-clinical development of these products. This document is currently open to public consultation and it’s very important that actors concerned with these products submit comments as these comments will serve as a basis for the development of future guidance.”
In your view, how long will it take to achieve a clear and practical regulatory framework for microbiome-based therapies in Europe?
“This question is difficult to answer as microbiome-based therapies are really diverse. For LBPs, the regulatory framework is quite clear today. The expectations from the regulatory authorities and the data requirement for clinical trial authorization or market authorization will again increase with the development of guidelines such as the one under development at the EMA level. For the more complex products, the data requirements are still unclear.
However, there is currently also major regulatory development such as the biotech act, with the ambition to facilitate clinical trials, development of in vitro diagnostics, and market access of innovation. These regulatory developments could also support the development of microbiome-based innovation, both for health but also for other fields of application such as environment and agriculture, and it is important to make sure that microbiome-based innovations are not inadvertently excluded from these regulatory developments.”
Overall, there is a clear momentum supporting progress in the field. As highlighted by the authors of the recently published review on European regulatory developments, there remain “a number of challenges that continue to impede the development and approval of microbiome-based therapies”. These include the complexity of clinical trial design, the lack of validated analytical methods, the absence of consensus on key definitions, such as “healthy microbiome”, the challenges associated with pharmacodynamic and pharmacokinetic assessments for microbiome-based therapies, the difficulty of translating pre-clinical findings into clinical settings, and, importantly, the substantial inter-individual variability in microbial composition. Nevertheless, EU Member States increasingly view initiatives such as the SoHO Regulation as an important opportunity to advance knowledge and improve patient access to microbiome-based therapies.
“Regulatory developments should also be viewed as opportunities: they signal recognition of emerging fields and can ultimately facilitate patient access to innovative therapies.”
As explicitly stated by Dr. Druart: “A new regulation, such as the SoHO Regulation, may initially be perceived as a burden by stakeholders who must adapt to new requirements. However, regulatory developments should also be viewed as opportunities: they signal recognition of emerging fields—such as the inclusion of the human microbiomes within the SoHO framework—and can ultimately facilitate patient access to innovative therapies.”
Notes:
*Concept paper is a document prepared by a European Medicines Agency working party prior to the drafting of a guideline, setting out the problem, the scope of the work, the resources needed and the timeframe.
References:
Rodriguez J, Cordaillat-Simmons M, Pot B and Druart C. The regulatory framework for microbiome-based therapies: insights into European regulatory developments. NPJ Biofilms Microbiomes 2025 doi: 10.1038/s41522-025-00683-0.
SoHO Regulation (2024/1938): SoHO Regulation – Public Health – European Commission
EU Pharma Package: EU Pharma Package: Final Texts officially published – ECA Academy
Horizon Scanning Report (EMA/204935/2022): Faecal Microbiota Transplantation – EU-IN Horizon Scanning Report
Concept paper (EMA/CHMP/30023/2026): Non-clinical development and evaluation of microbiome-based medicinal products – Scientific guideline | European Medicines Agency (EMA)
