Probiotics in Live Biotherapeutics: Innovations and Hurdles

Probiotics are skyrocketing in popularity. While they are classified as dietary supplements, probiotics are often being marketed and used to treat symptoms and illnesses despite not having FDA approval, which can lead to safety concerns for consumers. Enter Live Biotherapeutic Products (LBPs) – a groundbreaking shift in medicine that harnesses living microorganisms to treat, prevent, or cure diseases. Probiotics are poised to play a pivotal role in this transformation. This article explores some of the latest developments and challenges in the field of LBPs, with a focus on probiotics, to provide a comprehensive understanding of this evolving landscape.

Understanding the differences between probiotics and LBPs

Probiotics are defined by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” (National Institutes of Health, 2023). Probiotics come in different strains and are named based on genus, species, subspecies (if applicable), and an alphanumeric strain designation. Specific strains of probiotics are being studied for their health effects on humans. However, the FDA currently categorizes probiotics as dietary supplements, and they are not to be confused with Live Biotherapeutic Products (LBPs), which the FDA defines as “a biological product that: 1) contains live organisms, such as bacteria; 2) is applicable to the prevention, treatment, or cure of a disease or condition of human beings; and 3) is not a vaccine” (FDA, 2016).

Safety Concerns

The differences listed above are critical to note, as confusion between the two has had tragic results. The safety of probiotics, especially in vulnerable populations such as preterm infants, is a significant concern to the FDA. On October 26, 2023, the FDA issued Warning Letters to two companies that were illegally selling probiotics to prevent necrotizing enterocolitis in hospitalized preterm infants but instead contributed to invasive disease, which resulted in one infant death in 2023 and around 24 other adverse events since 2018 (FDA, 2023). The FDA emphasized the need for rigorous safety evaluations and warned “that if these products are used for the prevention or treatment of disease, they have not undergone the agency’s rigorous premarket process to evaluate their safety, effectiveness, and quality for these medical uses.”

Developments in LBPs

1. Clinical Applications: Probiotics are being investigated for a variety of medical conditions, including gastrointestinal problems, metabolic diseases, and even neurological disorders through the gut-brain axis. According to clinicaltrials.gov (2024), 227 clinical trials using probiotics as treatment have been completed in the US, with another 72 active or recruiting.  
2. Regulatory Advances: The FDA has been actively involved in advancing the science and regulation of LBPs. Recent approvals, such as Rebyota™ and Vowst™, highlight significant progress. Both treatments are used to prevent the reoccurrence of Clostridioides difficile infection (CDI) in patients 18 years or older following antibiotic treatment for CDI and recurrent CDI (rCDI).

Manufacturing Challenges

Producing LBPs, including probiotics, involves maintaining the viability and stability of live microorganisms throughout the manufacturing process. This requires controlled environments in the storage and manufacturing of LBPs. Having backup storage and environmental control units, generators for storage and processes, environmental monitoring systems, and implemented and tested emergency response procedures is critical to preventing loss. For more information on reducing risk with Change In Environmental Control, view BLS’ previous blog post about Scientific Property.

Analytical Challenges 

Characterizing probiotics as LBPs calls for sophisticated analytical techniques to ensure their potency, purity, and identity. According to Microbiome Therapeutics Innovation Group & Barberio (2024), these methodologies are still evolving, and standardization is needed to facilitate regulatory approval and clinical use.

Conclusion

The field of live biotherapeutic products, particularly probiotics, holds immense promise for advancing healthcare. The importance of properly marketing probiotics and following FDA practices for LBP approval cannot be overstated. Understanding these developments and challenges is essential to navigate the evolving landscape of LBPs and provide informed guidance to clients.

Authored by Medora West, Berkley Life Sciences, Sr. Life Sciences Risk Management Specialist