Live biotherapeutic products: the challenges and promises

Glenn Tillotson^*

• Independent researcher, North, United States

In the 4 th century BC Ge Hong, recognized the utility of fecally originated products "yellow soup" in managing diarrheal disease [1] In Europe, the first recorded use of Fecal Microbiome Transplantation (FMT) took place in veterinary medicine. The procedure was carried out by Fabricius Acquapendente (1537-1619), an Italian anatomist and surgeon, who transferred gastrointestinal content from a healthy animal to a sick one.Transfaunation', became a widespread treatment for animals and described its use for restoring normal rumination in cattle and in the last century the process has been used in veterinary medicine as transfaunation [2]. It is in the past decade that interest has reignited the restoration of the microbiome as a means of treating C. difficile infection (CDI) recurrences. In this supplement various aspects of this management process are discussed from a variety of perspectives. Prior to the approvals of these 2 LBPs there were significant challenges posed by regulators in terms of regulations and analytical frameworks. These are elegantly highlighted by the Microbiome Therapeutics Innovation (MITG) and Dadan Barberio (10.3389/frmbi.2024.1441290). It was clear that existing regulatory frameworks for governing LBPs had notable gaps. These gaps included microbial identification, potency and bioburdens. The MITG lead collaborative approaches in engaging experts in this field to hold discussions with the FDA. These meetings discussed catalyzing improvements in LBP analytics and refreshing the regulatory landscape. It was clear that a multi-faceted approach to continued development LBPs is essential. Van Dijk et al discussed the challenges faced with expanding the evolution of LBP development and ensure product safety and effectiveness. Previous recent experiences of non-regulated fecal materials for transplantation were associated with infections leading to some deaths notably in immunocompromised patients. Thus, moving from traditional methods to developing safe products for use in fecal transplantation to live microbial products (LMP).. LMPs are sub-divided into specific subcategories and the product characteristics lead to the development of appropriate guidelines. LMP are in the GMPcompliant manufacturing guidance. However, for injectable LMPs the agencies do not have regulatory guidelines as sterility is required. Clearly this is inappropriate for LMPs. Safetyrelated quality analysis is often inappropriate. However, recent FDA guidance has detailed 29 pathogens which must be absent from currently approved LBPs. This list is updated as necessary. Van Overall Live Biotherapeutic Products hold significant promise as therapeutic or preventative options to an array of human diseases and conditions. The development of these products is subject to evolving regulatory including manufacturing processes and safety needs. As these become more defined LBPs follow on the work of Ge Hong and his "yellow soup".