Differentiating Between Live Biotherapeutic Products and Conventional FMTs

Live biotherapeutic products (LBP) have become a significant class of agents in treatment for recurrent Clostridium difficile.

According to the FDA, LBP are defined as: “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.”

Currently, there are 2 LBPs that are FDA approved: Ferring's Rebyota (fecal microbiota, Live-jslm) and Seres' Vowst (fecal microbiota spores, live-brpk).

Within the LBP space, there are 2 different modalities for delivery of these agents including oral capsules and fecal microbiota transplants (FMTs). The latter method can present challenges if not properly vetted. Donor banks lack standardization or government oversight, and the process of capturing feces can present issues.

“The FDA noted that centralized manufacturing in stool banks presents safety concerns, namely the transmission of infectious pathogens related to the number of patients that may be exposed to a particular donor and particular manufacturing processes and particles,” said Ravina Kullar, PharmD, MPH, FIDSA, infectious disease consultant.

“In 2022, the FDA was informed of the potential risks of FMT. There were 6 patients who received a stool bank supplied FMT product for CDI…And there were 2 patients that developed enteropathogenic E coli and there were 4 patients that develop Shiga toxin-producing E coli (STEC) Infections," Kullar said. "Four of those 6 patients required hospitalization, and there were 2 patients that died...So you can see with these 6 cases with pretty pathogenic organisms, that this was quite concerning to the FDA."

Kullar explains that the key differentiators from live biotherapeutic products and conventional FMT include donor and pathogen screening, good manufacturing practices, and rigorous clinical trials. Donor banks are not required or set up to ensure there are no issues with donors’ health.

“Currently, there is no standardization of the FMT process. And the implementation of FMT honestly just varies depending on what institution and site that you're at,” Kullar said. “FMT basically depends on the donors, and it depends on their fresh feces, which really restricts the application of FMT, as the technology to keep fecal microbiota alive, has really not been perfected quite yet. It's also unclear as to what microorganisms of FMT are effective to treat various conditions that the FMT is currently used in.”

On the other hand, Kuller says that LBP are FDA approved because they have gone through rigorous clinical trials and have shown a favorable safety profile and efficacy in treating recurrent C difficile. And they continue to do follow-up studies to ensure long-term these products remain effective and safe.

Contagion spoke to Kuller recently and she offered further insights about the differences between LBP and standard FMTs.