Live biotherapeutic products: the importance of a defined regulatory framework

Abstract

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.

Lactic acid bacteria as probiotics for the nose?

“…Overall, for next-generation probiotics, such as the more recently suggested D. pigrum, the safety profile is less well-known and animal studies are thus of more interest to evaluate the safety before clinical studies are performed (Cordaillat-Simmons et al, 2020;Rouanet et al, 2020). The more traditional strains, especially strains that belong to the Lactobacillaceae, are already used on a large scale and have an established safety profile, hence animal studies might not be essential before proceeding to clinical trials in humans.…”

Batch Culture Formulation of Live Biotherapeutic Products

“…[24] Larger manufacturing scale-up with detailed characterization of film components and batch-to-batch consistency are still needed to confirm the potential of LBP-films to satisfy regulatory guidelines and future clinical investigation. [25] Figure 6. Storage characterization and performance of BCF LBP-films.…”

Cell therapies in the clinic

“…Distinct from consortia‐based therapies, single strain therapies are currently in clinical trials for indications including bacterial infections, inflammatory diseases, metabolic disorders, cancer, and others. Unlike consortia‐based therapies, single strains offer more controlled and defined pathways for the discovery of specific pharmacological mechanisms of action, genetic engineering, formulation development, and consistent manufacturing, thereby reducing complexities for key regulatory considerations 104 . Single, donor‐derived strains constitute 56% of the microbe clinical trials.…”