MHRA position on UK licensing route for microbiome-based medicines

Microbiome-Based Medicinal Products (MBMPs) are emerging as an exciting new class of therapies, defined by the MHRA as medicinal products intended for the prevention, treatment, or diagnosis of disease in humans, whose principal therapeutic effect is mediated through the modulation, restoration, replacement or functional activity of the human microbiome, and which contains as active substance(s) live microorganisms, a defined consortium of microorganisms, a complex microbial ecosystem, or non-viable microorganisms or their derived components. Unlike fecal microbiota transplantation (FMT), which involves the transfer of complex donor-derived microbial communities, MBMPs are manufactured medicinal products with defined composition, quality controls, and clinical development pathways.

Interest in MBMPs continues to accelerate globally. The United States has already licensed two MBMPs indicated to prevent the recurrence of Clostridioides difficile infection (REBYOTA and VOWST), paving the way for a growing number of clinical development programs. In Europe, regulators are also responding to increasing innovation, with MBMPs of human origin being considered within the broader framework of the new Substances of Human Origin (SoHo) Regulation.

The UK has likewise recognized the growing importance of this field and recently published a position paper by the MHRA outlining its approach to MBMP regulation. The MHRA confirms that MBMPs fall within the existing UK medicines regulatory framework established under the Human Medicines Regulations 2012. Depending on their characteristics, these products may be regulated as biologics or, in certain circumstances, as Advanced Therapy Medicinal Products (ATMPs), triggering additional regulatory considerations (e.g., genetically modified organism (GMO) notification).

While the position paper provides useful insight into the scientific and regulatory aspects developers should consider, there remains no dedicated UK guidance specific to MBMPs. Instead, the MHRA strongly encourages early engagement through its Innovation Office and Scientific Advice services to discuss development strategies and obtain product-specific regulatory guidance.

Some important questions remain. Further clarity on the regulatory approach to genetically modified microbiota, particularly those engineered for gene delivery applications, would be valuable. While most UK clinical trials using genetically modified organisms (GMOs) are expected to fall under Contained Use (CU) GMO requirements, live genetically modified microbiota with the potential for environmental shedding, persistence, or proliferation may require consideration under Deliberate Release (DR) regulations.

The MHRA position paper also highlights that, from a Chemistry, Manufacturing and Controls (CMC) perspective, MBMPs present unique challenges. Developers must address variability in starting materials, demonstrate adequate product characterization, establish robust manufacturing controls, and develop analytical methods capable of supporting product quality throughout development and commercialization.

At Boyds, we have extensive experience supporting innovative and non-conventional therapeutic modalities. By applying a science- and risk-based approach, we help developers navigate complex CMC and GMO requirements, enabling efficient progression through regulatory development pathways for these novel microbiome-based therapies.