Metabiotics: Regulatory Perspective on Non-viable Microbiome-based Therapeutics

Metabiotics are Non-viable Microbiome-based Therapeutics composed of microbial-derived metabolites or structural components with clearly defined biological activity, and do not include live microorganisms. They are structurally and functionally distinct from conventional live biotherapeutic products (LBPs). Based on these characteristics, this study sought to examine the applicability of the current live biotherapeutic-centered regulatory framework to Metabiotics and to propose the need for independent evaluation criteria. To achieve this, the guidelines of major regulatory agencies—including the United States (FDA), Europe (EMA), Korea (MFDS), Japan (PMDA) and Australia (TGA)—were compared and analyzed, along with case studies of marketed products such as RebyotaTM and VowstTM. Differences in structure, mechanism of action, and evaluation items between live biotherapeutic products and Metabiotics were identified. Furthermore, by examining the MFDS’s independent guideline for extracellular vesicle therapeutics (EVTPs), which are non-living biological products, this study explored evaluation metrics applicable to Metabiotics. The analysis revealed that directly applying live biotherapeutic-centered standards to Metabiotics has limitations, and the establishment of a separate regulatory framework tailored to product characteristics is necessary. It is expected that this study will serve as foundational material for the future institutional establishment and development of an evaluation system for Metabiotics.