Contemplating Regulatory Frameworks for FMT

One of the most serious health care-associated infections that continues to plague health care facilities worldwide is Clostridium difficile (C. diff) infections (CDI). What makes C. diff such a great public health threat is that 20% of those who get infected will experience recurrent infection. And, when it comes to CDI recurrence, there aren’t many effective treatment options available. One controversial method, however, continues to yield positive results: fecal microbiota transplantation, or FMT.

With FMT becoming more widely used for the treatment of recurrent CDI, researchers are calling for an appropriate regulatory framework to be established. Luckily, authors of a Policy Forum published in Science magazine have aimed to do just that.

FMT remains a controversial topic in the health care sphere because not much is known about the long-term effects of the process on the gut microbiome. The process—which entails extracting healthy bacteria from an uninfected individual’s fecal matter, processing it, and directly transferring that bacteria into the infected patient—aims to restore a normal gut bacteria population in the infected patient, and thus, discourage the growth of C. diff.

Although FMT is thought to be an effective treatment for recurrent CDI, the logistics of delivering the stool product limits its widespread use. It is for these reasons that some investigators have been working on delivering the treatment in a less-invasive pill form. It is also why some individuals are starting to self-administer FMT, using unscreened stool samples which have not been assessed for disease.

“The current regulatory framework arguably does not adequately regulate stool banks,” Diane E. Hoffmann, JD, Jacob A. France Professor of Health Law and director of the Law & Health Care Program at the University of Maryland Carey School of Law told Contagion^®. “While major catastrophic outcomes (death or severe illness) have not been reported as a result of use of stool from stool banks in the United States, there is the possibility that such stool might not be adequately screened for communicable diseases or that the preparation and packaging of the stool might not be done with good manufacturing practices,”

In the Policy Forum, the investigators channeled their efforts into outlining “key areas for improvement” compared with the regulatory approaches to FMT that exist currently, according to a recent press release.

“The current exercise of enforcement discretion allows patients with C. diff who have not responded well to standard therapies access to stool but doesn’t capture data about the longer-term effectiveness or side effects of FMTs. Also, the practice of enforcement discretion leaves market players with some uncertainty about future regulatory actions that might be taken and whether they should enter the market,” Professor Hoffmann explained to Contagion®. “The US Food and Drug Administration has proposed a change to its current practice, which is to require stool banks to obtain an investigational new drug application for marketing of stool which may reduce patients’ treatment access to stool, even for C. diff. They would only get access through a clinical trial and could be given a placebo rather than the actual treatment.”

In an attempt to address these issues, the members of the Policy Forum developed an alternative approach. “Our approach would treat stool from stool banks like tissue or blood,” Professor Hoffmann said. “Stool banks would be regulated like tissue banks with appropriate modifications for stool. Donors would have to be screened. Stool would have to be screened and tested. We think our approach would also reduce the number of people who would likely do the procedure at home when access to stool is reduced. The concern with DIY procedures is that the donor and stool are unlikely adequately screened and tested.”

It is the hope that taking this new approach when it comes to regulating FMT therapy—which is quickly becoming the standard-of-care for the treatment of recurrent CDI—will help make the therapy more accessible to those who need it.

As for next steps? “A representative from the FDA sat in on our Working Group sessions and has been part of our process. We have another meeting of the Working Group scheduled for February in which we plan to discuss next steps,” Professor Hoffmann said.