A working group of human microbiome researchers and legal experts developed what they say is an improved regulatory process for faecal microbiota transplantation (FMT) which will result in better outcomes for patients and could serve as a model for other countries contemplating regulatory frameworks for FMT.
The use of FMT, the transfer of stool from a human donor to a human recipient, for recurrent Clostridium difficile infection (CDI) is considered by many to be standard-of-care therapy, but its regulation is in the early stages. CDI is the most common healthcare associated infection in the US, with an estimated 453,000 cases and 29,000 deaths per year. However, inconsistencies on how to regulate its treatment with FMT abound as the transplanted material is not your “typical” drug and may not be appropriate for the traditional drug regulatory pathway.
In a recently published policy forum, co-authors Diane Hoffmann, Jacob A France professor of health law and director of the Law & Health Care Programme at the University of Maryland Francis King Carey School of Law, and colleagues, Dr Erik von Rosenvinge, Dr Jacques Ravel and Dr Mary-Claire Roghmann, from the School of Medicine, Dr Frank Palumbo, from the School of Pharmacy, and Dr Virginia Rowthorn, from the University of Maryland, Baltimore Office of Research and Development, argue that a regulatory framework for the increasingly popular treatment must balance the need for more information on effectiveness and safety with appropriate access for patients.
The co-authors recommended a three-track framework calling for increased oversight as the stool product is increasingly manipulated prior to transfer. Under track 1, when FMT is performed by a physician with stool from a known donor, it would be regulated as the “practice of medicine” and subject to state regulation. Under track 2, stool would be obtained from a stool bank regulated in the same manner as human/cell tissue establishments, which would include registering with the FDA and complying with rules for donor testing.
Track 3 would be for “modified stool products” such as stool processed in such a way that the original relevant characteristics of the transferred community of microorganisms have been altered. These products would be regulated in a manner similar to how FDA currently regulates biological products.
“The implications for people who suffer with C. difficile that’s not responsive to standard therapies is great,” said Hoffmann. “Long term access to treatment would be limited under proposed FDA guidelines,” she continued.
In the last four years, the FDA has struggled to regulate FMT, shifting its position several times and in recent draft guidance appearing to want more data to establish the effectiveness of the treatment.
Hoffmann and her colleagues believe their three-track regulatory framework would be relatively easy to implement and would improve patient outcomes and access by regulating stool banks and tracking data.
The Human Microbiome Project and similar research has generated great interest in potential health benefits of microbiota transplantations (MTs). The use of fecal microbiota transplantation (FMT), the transfer of stool from a human donor to a human recipient, for recurrent Clostridium difficile infection (CDI) is considered by many to be standard-of-care therapy, and data on its safety and effectiveness are accumulating (1–3). Yet, although some physicians are practicing FMT using stool from donors known to the physician or patient, stool is inconsistently screened for infectious pathogens. The use of prescreened stool obtained from a stool bank and shipped to the physician is increasing, but the stool banks are not regulated. Patients who self-administer FMT using unscreened stool sourced from family or friends is also widely described. In consideration of these and other particular characteristics and challenges of MT, and the nascent regulatory landscape, we convened human microbiome researchers, legal experts, and others to explore regulatory pathways for MT (4). We believe our proposed approach is an improvement on the U.S. Food and Drug Administration’s (FDA) current and proposed scheme and could provide a model for other countries that are contemplating regulatory frameworks for FMT.
Diane Hoffmann, Francis Palumbo, Jacques Ravel, Mary-Claire Roghmann, Virginia Rowthorn, Erik von Rosenvinge