As fecal microbiota transplantation gains traction in the medical world, regulators may need to step in.
Your feces could be used to treat patients.
The human gut microbiome—the genetic material of all microbes living in the human gut—is considered “essential for human development, immunity and nutrition.” Some clinical researchers have sought to harness the power of the human gut microbiome to treat certain diseases through a procedure called fecal microbiota transplantation (FMT).
During an FMT procedure, doctors transfer stool from a healthy donor to the gut of a patient. Doctors now use FMT to treat diseases such as Clostridioides difficile, which causes severe diarrhea and inflammation of the colon.
Although people have used FMT since the fourth century, researchers did not conduct the first randomized controlled trial of FMT until 2013. That study indicated that FMT could help treat patients with C. difficile infections more effectively than antibiotics alone.
Since then, other clinical studies have confirmed that FMT is an effective treatment for C. difficile infections, and researchers have begun to examine other applications for FMT. Some scientists question the safety of FMT, but the medical community has largely accepted it as a treatment for patients with recurrent C. difficile infections or for patients with infections that do not respond to other treatments.
Stool samples for FMT come from either patient-selected donors or stool banks. Stool banks are specialized centers that recruit and screen donors, process donations for use in FMT, provide samples to clinicians and researchers, and collect and record safety data. Currently, regulators have not specifically targeted stool bank operations.
In 2013, FDA released a guidance document detailing its policy regarding investigational new drug (IND) applications for the use of FMT to treat C. difficile infections. The guidance was released for immediate implementation, so it went into effect without a public comment period. Under this policy, FDA considers FMT in any context to be an investigational treatment.
In its guidance document, FDA announced that it will exercise enforcement discretion—meaning that FDA would not require IND applications for FMT when used to treat C. difficile infections that do not respond to standard therapies. FDA still requires clinicians and researchers to submit an IND application to use FMT for any other purpose, including in safety studies.
In its 2013 guidance, FDA explained that it will only exercise its enforcement discretion if health care providers obtain informed consent. As a part of the informed consent process, health care providers must disclose that FMT is investigational and discuss the reasonably foreseeable risks of FMT.
FDA has published two draft guidance documents since 2013, but neither draft has been implemented. The most recent of these draft guidance documents, issued in 2016, would revise the 2013 policy. Under the 2016 draft, FDA would still support enforcement discretion for FMT when used with informed consent to treat C. difficile infections that do not respond to standard treatment, but it would also implement new limitations.
Under the 2016 draft guidance, for example, health care providers using FMT would not be able to use stool from a stool bank. Instead, the health care provider administering FMT would have to oversee the stool collection. As a part of the collection process, health care providers would need to screen and test both the donor and the donated stool. Providers seeking to use FMT to treat other diseases would be required to go through the regular IND process.
FDA is currently reviewing comments on its 2016 draft guidance. Until FDA implements a new guidance document, the 2013 policy will remain in effect.
In addition to its 2013 guidance and 2016 draft guidance, FDA has released several safety alerts about the risk of infection from the use of FMT. In safety alert released in 2019, FDA also set new donor screening and sample testing requirements for IND holders and applicants.
Some scholars predict that FMT may only be available temporarily, either because FDA will approve a microbiota-based drug that is more effective than FMT, or because restrictions on stool banks—such as those proposed in the 2016 draft guidance—prevent access to the treatment.
If FMT treatment and research do continue, FDA may need to develop new regulatory pathways to regulate FMT effectively. Currently, FDA regulates FMT as a biologic drug. Scholars argue that this approach will limit access to treatment because the human gut microbiome is dynamic and therefore difficult, if not impossible, to characterize with the specificity that is normally required for biologic drugs. Instead, some experts suggest that FDA should adopt a hybrid regulatory model for FMT similar to human tissue regulation.
As novel medical treatments and biotechnologies continue to develop, FDA will face new challenges that may not fit into its traditional regulatory models. In the context of FMT, FDA may need to change the way that it approaches regulation to prioritize patient safety without inhibiting clinical innovation.