Should Fecal Microbiota Transplants Be Regulated as Drugs or Organ Donations?

The FDA is anticipated to release a finalized guidance document any day now around the regulation of fecal microbiota transplants (FMT) for the treatment of Clostridium difficile infection (CDI). This guidance could have large implications for the pharmaceutical industry because the FDA will decide to regulate the treatment either as investigational new drugs (INDs), or as a kind of organ donation. The outcome will dictate how they’re priced, who oversees their use, and who can make money off of the treatment.

In July 2013, the FDA announced that it would exercise enforcement discretion when FMT was used to treat patients with CDI who were not responding to standard therapies. “FDA plans to exercise this discretion provided that the treating physician obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products,” wrote the FDA.

In 2014, the FDA released a draft guidance document announcing that fecal microbiota would be regulated as a drug. Therefore, all uses of FMT would need to be included in an IND application and it would require all patients who wanted to be treated with FMT for recurrent CDI to be enrolled in a clinical trial in order to do so. Providers submitted comments on the draft guidance arguing that the available evidence (including 1 randomized clinical trial that was stopped early because 94% of patients in the FMT arm were cured) was too positive and persuasive to restrict its availability to clinical trials.

For 3 years, the FDA functioned under this enforcement discretion guideline until March 2016 when it released a new draft guidance document. Under this guideline, the FDA rescinded its enforcement discretion policy for stool banks, requiring them to submit an IND to obtain and distribute stool. The FDA also required that, “the stool donor and stool are qualified by screening and testing performed under the direction of the licensed healthcare provider for the purpose of providing the FMT product for the treatment of the patient.”

Currently, patients treated with FMT use stool banks such as the nonprofit OpenBiome, which performs screening and testing procedures on the FMT product that is then distributed to providers. At present, OpenBiome supplies most of the fecal matter for transplants in the United States. Under the draft guidance announced in 2016, the FDA surmised that hospitals are permitted to independently screen and test FMT donors and treat patients in the hospital with FMT, which would vastly disrupt the centralized system of stool processing in place at present.

Critics of FMT regulation as an IND argue that the approach is based on outdated science and recommend an alternative regulation process. “Our key recommendations are that FDA treat stool for FMT as a tissue rather than a drug/biologic; that stool banks be regulated like tissue banks with requirements for donor testing and screening and compliance with ‘good manufacturing practices’; that FDA establish or fund a registry and stool banks be required to report adverse events and data on outcomes to the stool bank,” said Diane E. Hoffman, JD, MS, the Jacob A. France Professor of Health Law and director of the Law and Health Care Program at the University of Maryland Carey School of Law, said in an interview with Healio.

Hoffman also explained that the proposed regulations offered in the 2016 draft guidance document would “likely limit patient access” to the treatment.

Hoffman is not alone in this thinking. Since the publication of the draft guidance, more than 40 well-known gastroenterologists and infectious disease clinicans wrote to the agency, urging it to rethink its approach.

However, supporters of the regulation, largely pharmaceutical companies and providers, argue that regulating FMT as a drug will help to ensure the efficacy and long-term safety of the therapy. Currently, there are no long-term records of adverse events because the FDA has yet to determine regulation guidelines.

Beyond that, experts in bioethics as well as healthcare professionals are calling on the FDA to create a new regulatory category that reflects the cutting-edge field of microbiota therapies, which are currently being studied as potential treatments for ulcerative colitis, obesity, and autism, among others.

According to the latest report from Global Data, the CDI market is set to grow from $630 million in 2016 to almost $1.7 billion by 2026. However, until the FDA approves the therapy, many insurance companies still refuse to cover it.

In a poll published by STAT News, when readers were asked if FMT should be regulated as drugs or a kind of organ donation, 54% reported they believed the FDA should consider fecal matter—derived therapies as injectable drugs while 46% believed they should be regulated as organ-like donations.