New live biotherapeutics will require regulatory and scientific innovation: the importance of a defined regulatory framework

Live Biotherapeutics developers will need to incorporate gold-standard pharmaceutical development techniques and approaches in order to reach market and patients in need

The Pharmabiotic Research Institute (PRI), Europe’s only regulatory expertise centre for the development of microbiome-based drug products, has announced the publication of a review titled “Live biotherapeutic products: the importance of a defined regulatory framework. Published in the journal Experimental & Molecular Medicine, it shines a light on the need for clear scientific and pharmaceutical standards when developing and registering live biotherapeutic products (LBPs), a new and innovative type of microbiome-based drug product. Many in the general public will have heard of ‘probiotics’, which according to the WHO definition are ‘live microorganisms that when administered in adequate amounts confer a health benefit on the host…’; however the authors of this review have focused on live microorganisms as active pharmaceutical substances intended to be used in the treatment or prevention of disease in humans. It is an in-depth treatment of the latest regulatory innovations and ‘quality-by-design’ development principles which will be critical in the appropriate assessment of these biologic medicines’ quality, efficacy and safety. This work draws on years of interactions with leading biotechs in the field, discussions with national and European health authorities (mainly through scientific advice), as well as extensive research of the existing European and other regions’ relevant pharmaceutical frameworks. The PRI is a European non-profit organization, and this topic is a key example of the type of regulatory challenges that its members are striving to overcome in their pursuit of microbiome medicinal product development and registration for the EU Market.

Early adoption of the “Intended Use” principle is crucial to these products’ success

Ideally, this article will help stakeholders in the field of microbiome-based products understand that the active substance or the ingredient of a product does not define its regulatory status. Thus, ‘probiotic’ substances can be developed as dietary supplements, food ingredients or drugs, depending on what these substances are intended to do and to whom,” says co-author Dr. Alice Rouanet (PRI).

Quality by Design – past challenges in other fields can help to guide this new industry

Dr. Magali Cordaillat-Simmons, Executive Director of the PRI continues, “In a field where regulatory confusion often exists we perceived a strong need for clarification of the general concepts and specific constraints associated with ‘probiotic strains’ intended for prevention or treatment of a human disease, i.e. in the context of their registration as biological drug products.”

Similar to all products intended to prevent or treat diseases, LBPs will have to be registered as medicinal products to reach market in the US and in Europe. LBPs under the current European legislative framework have no ‘separate status’, and “…are by nature considered biological medicinal products as the active substances are live microorganisms, which are biological substances…LBPs have to comply with the biological medicinal product legislative and regulatory framework.” The authors address several aspects of pharmaceutical development principles, notably; ‘How can the quality of LBPs be ensured and demonstrated?’, ‘How can the safety of LBPs be demonstrated?’, and ‘How can the efficacy of LBPs be demonstrated?’.

Regulatory uncertainty as an opportunity to engage directly with Health Authorities

Pr. Bruno Pot, Science Director for Yakult Europe and PRI President concludes, “New medicinal products directed to the gut microbiota pose big scientific challenges, because of the complexity and variability of the microbiota. The regulatory challenge, however, is also real, maybe because of the complexity and variation of the possible paths to success! Time and money can be gained in making decisions as early as possible on the regulatory path to follow: it will help to decide on the study planning and result in the preparation of a valid and credible dossier for the evaluation by competent authorities. Our hope is that this paper could assist you somehow in this complex process.

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Review article published in Experimental & Molecular Biology: Live biotherapeutic products: the importance of a defined regulatory framework