AGA’s microbiome leaders recently met with representatives from FDA’s Center for Biologics Evaluation and Research (CBER) to share clinician and researcher perspectives on fecal microbiota transplantation (FMT) and understand CBER’s current thinking on the regulation of FMT for the treatment of Clostridioides difficile (C. difficile) infection. Here are the key takeaways from AGA’s discussion with CBER.
AGA made clear to FDA the needs and concerns of the clinical and research communities regarding FMT. AGA communicated clinician concerns about patient access to whole-stool FMT being restricted or perhaps eliminated once drugs containing live microbials are FDA-approved. AGA’s representatives also shared concerns about the narrow inclusion criteria for current clinical trials and whether the new drugs will be as effective as whole-stool FMT for vulnerable populations such as the elderly or immunocompromised, who make up the majority of patients with C. difficile infection but are often excluded from current trials. Finally, AGA emphasized the need to encourage innovation in product development and the importance of performing controlled safety and efficacy studies on products that can be manufactured predictably and reproducibly.
All stakeholders agreed that the AGA FMT National Registry is an important effort to collect short- and long-term data on the safety and efficacy of FMT. AGA will maintain dialogue with CBER regarding data from the registry and lessons learned. Clinicians practicing FMT are strongly encouraged to participate in the FMT National Registry, which will follow short- and long-term outcomes of patients receiving FMT for up to 10 years. The registry is funded by a grant from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (award number R24 AI118629) and is a partnership of AGA, Crohn’s and Colitis Foundation, Infectious Diseases Society of America and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
CBER is currently working on an update to the enforcement discretion policy on the use of FMT for C. difficile infection not responsive to standard therapies. Agency representatives noted that all comments will be considered as the agency finalizes the guidance. The current enforcement discretion policy has been in place since July 2013 and was most recently updated by CBER in a draft guidance in March 2016. The policy enables clinicians to use FMT for the treatment of C. difficile infection not responsive to standard therapies without having an investigational new drug (IND) application in place.
Human stool will continue to be regulated as a drug and biological product. The agency stated human stool does not meet the definition of a tissue and FDA does not intend to change how it is currently classified.
CBER is interested in hearing ideas for novel trial designs that may help address the challenges of patient recruitment for clinical trials in C. difficile infection and other indications for FMT.
AGA encourages members to share their thoughts on this topic through the AGA Community.
Following AGA’s meeting with CBER, FDA issued a safety alert due to the death of a patient who died from a FMT containing a multi-drug resistant organism. The agency has since issued additional requirements for IND holders on stool donor screening. AGA will continue to engage with FDA on this issue and share updates as they become available with all members.
Meeting participants from AGA membership:
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- Gail A. Hecht, MD, MS, AGAF, immediate past chair, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board
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- Colleen R. Kelly, MD, co-chair, AGA FMT National Registry Steering Committee
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- Alexander Khoruts, MD, member, AGA Center for Gut Microbiome Research and Education Scientific Advisory Board
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- Gary D. Wu, MD, AGAF, basic research councilor, AGA Institute Governing Board, and member, AGA FMT National Registry Steering Committee
Meeting participants from FDA/CBER:
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- Peter Marks, MD, PhD, Director, CBER
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- Celia Witten, PhD, MD, Deputy Director, CBER
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- Diane Maloney, JD, Associate Director for Policy, CBER
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- Julie Tierney, JD, Senior Policy Advisor for Strategic Planning & Legislation, CBER
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- Marion Gruber, PhD, Director, Office of Vaccines Research and Review (OVRR), CBER
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- Theresa Finn, PhD, Associate Director for Policy, OVRR, CBER
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- Doran Fink, MD, PhD, Deputy Director, Clinical, Division of Vaccines and Related Products Applications, OVRR, CBER
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- Paul Carlson, PhD, Senior Staff Fellow, OVRR
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- Lorrie McNeill, Director, Office of Communication, Outreach and Development, CBER
This meeting took place on May 6, 2019, at the FDA headquarters in Silver Spring, Maryland.
