EMA proposes new microbiome reflection paper amid growing interest

The European Medicines Agency (EMA) has published a concept paper outlining topics that it wants to address in a reflection paper on non-clinical development of microbiome-based medicinal products (MMP). The agency said the paper should address issues such as the diversity of MMPs and the different areas of the body they target.

EMA said that MMPs differ from other pharmaceutical products in many ways, raising unique challenges and requiring special considerations. It also noted growing interest in developing MMPs, which prompted the agency to identify aspects unique to MMPs that need to be addressed in a reflection paper.

"Currently, there is no regulatory framework for the non-clinical evaluation of microbiome-based medicinal products," said EMA. "Conventional pharmacological and toxicological approaches are often not fully applicable, particularly regarding biodistribution, safety, and the use of standard in vivo pharmacodynamic models to support dose selection and efficacy evaluation.

"The absence of tailored information may lead to increased uncertainty for developers, inconsistencies in regulatory submissions and evaluation, and potential delays in product development," the agency added.

On 2 March, EMA published a concept paper intended to lead to a reflection paper on the regulatory questions MMP manufacturers should consider when developing their products. The agency said the reflection paper would ultimately lead to a harmonized approach to regulating MMPs across the European Union for clinical trials and marketing authorization applications.

EMA said that it plans to address questions about product and target diversity in the reflection paper, since MMPs can range from fixed product compositions to tailored therapies and may target human-associated microbiomes across various body sites. It also said it will provide clarity on pharmacological models.

"Standard animal disease models may lack relevance for MMPs due to species-specific microbiome effects and limited translatability," said EMA. "Alternative models and New 84 Approach Methodologies (NAMs) may be considered."

Finally, EMA said the paper will address safety considerations that reflect unique safety challenges and noted that conventional toxicity testing may not be appropriate in MMP development.

"Careful consideration is required regarding biodistribution (including potential translocation), persistence, degradation or elimination pathways, and the possibility of shedding," the agency added.

EMA said the reflection paper will cover three broad types of MMPs, including live biotherapeutic products (LBPs), whole/highly complex ecosystem-based products, and non-living MMPs. The agency also listed five types of products that will not be covered in the reflection paper and explained its rationale, including human microbiota transplantation, MMPs containing genetically modified microorganisms as active substances, microorganism-containing products that are not intended to prevent or treat disease, microorganisms used in vaccines or other standard immunological products, and phage therapy and other virome-based approaches.

Concept paper

EMA proposes new microbiome reflection paper amid growing interest

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