Live biotherapeutic products: the importance of a defined regulatory framework.

Probiotics have been defined as “Live microorganisms that when administered in adequate amounts confer a health benefit on the host”. This definition covers a wide range of applications, target populations and (combinations of) microorganisms. Improved knowledge on the importance of the microbiota in terms of health and disease has further diversified the potential scope of a probiotic intervention, whether intended to reach the market as a food, a food supplement or a drug, depending on the intended use. However, the increased interest in the clinical application of probiotics may require specific attention given their administration in a diseased population. In addition to safety, the impact of the type of product, in terms of quality, production method and, e.g., the acceptance of side effects, is now part of the current regulatory constraints for developers. In the European Union, foods are regulated by the European Food Safety Authority and drugs by the European Medicines Agency; in the United States, the Food and Drug Administration (FDA) deals with both categories. More recently, the FDA has defined a new “live biotherapeutic products” (LBP) category, clarifying pharmaceutical expectations. Since 2019, the quality requirements for this category of drug products have also been clarified by the European Pharmacopoeia (Ph. Eur.). Similar to all products intended to prevent or treat diseases, LBPs will have to be registered as medicinal products to reach the market in the US and in Europe. In this area, regulatory authorities and the pharmaceutical industry will routinely use guidelines of the “International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use” (ICH). Although ICH guidelines are not legally binding, they provide very important recommendations, recognized by almost all drug authorities in the world. In this review, we discuss some aspects of this regulatory framework, especially focusing on products with an intended use in a diseased or vulnerable target population. Regulatory frameworks must be stretched to include microbe-based medicines such as “live biotherapeutic products” (LBPs). Some LBPs are similar by nature to probiotics, health-enhancing living microbes, except that they are meant to treat or prevent disease in sick or vulnerable individuals. Bruno Pot at the Vrije Universiteit Brussel in Belgium and co-workers have reviewed how current food and drug regulations in the United States and the European Union apply to living microorganisms. As for all drugs, in the case of LBPs, quality, safety, and efficacy must be demonstrated, but LBPs pose extra challenges because they contain live organisms, raising issues of stability over time and batch-to-batch variation. Differences in patients’ microbiomes and diets add further complications. This review helps to outline a way forward in this new and developing field of medicinal products.