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Microbiome Resource Center

December 20, 2017
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FDA should view FMT donor stool as tissue, regulate stool banks, experts say

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In a policy piece published in Science, experts critical of the FDA’s recently proposed regulations for fecal microbiota transplantation recommended an alternative framework that they said would ensure safety without restricting access to this effective treatment for Clostridium difficile infection.

“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,” Diane E. Hoffmann, JD, MS, the Jacob A. France Professor of Health Law, and director of the Law & Health Care Program at University of Maryland Carey School of Law, told Healio Gastroenterology and Liver Disease in an email.

As we reported earlier this year, the FDA’s most recent draft guidance would rescind its 2013 enforcement discretion policy for stool banks, requiring them to submit an investigational drug application (IND) to obtain and distribute stool. This would apply to physicians using stool from stool banks for the treatment of C. difficile infection that does not respond to other therapies, Hoffmann said.

“Although the current regulations allow patients access to stool from stool banks for treatment of C. diff that is not responsive to standard therapies, the stool banks are not regulated,” Hoffmann said. “The current regulations are not as much of a problem as FDA’s proposed regulations, however, which will likely limit access to these patients by requiring that they be enrolled in a clinical trial in order to gain access to the stool. Such a trial might mean that they are in a placebo arm rather than the treatment arm.”

Such patients concerned about receiving a placebo, or those who are ineligible to participate in the trial, may instead do the procedure themselves, which increases the risk for infectious disease transmission, or they may continue to take less effective antibiotics and contribute to antibiotic resistance, Hoffmann and colleagues wrote.

Other critics of the FDA’s draft guidance argued that many hospitals and local laboratories lack the resources to screen donor material as quickly and rigorously as stool banks, and as screening is expensive and not reimbursed by all payers, the policy would hit poor patients the hardest, they noted.

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Proposed alternative

To overcome these problems, Hoffmann’s group proposed a three-track regulatory framework, that attempts “to provide continued access for patients and more data on safety and effectiveness for regulators and providers, while requiring research on applications of FMT other than CDI.”

First, they argued that FMT should be regulated as the “practice of medicine” when physicians treat patients for CDI using donor material not acquired from a stool bank, though an IND would be required for other indications, unless they meet “clinical innovation” criteria (ie, terminal or life-threatening conditions).

Second, they argued that stool banks should be regulated the same as human cell-tissue establishments with some added oversight, including annual registration with the FDA and complying with donor screening and testing rules and “good manufacturing practices.” They said stool banks should also be required to report safety data to the FDA and outcomes data to a national registry, and that they should only be able to provide donor material for CDI not responsive to standard therapies without an IND.

Third, they argued that “modified stool-based products” should be regulated as biological products or drugs, with some changes to IND requirements.

Hoffman and colleagues noted that their proposals would allow stool banks to continue to provide stool but only under an approved regulatory framework, and that unlike the FDA’s current enforcement discretion policy that has no data collection requirements, their proposal would mandate ongoing collection of outcomes data.

“Stool banks are not currently regulated,” Hoffmann said. “There are potential risks of disease transmission via fecal transplants [and] there may be long term effects of FMT that gastroenterologists should be aware of.”

However, they noted a potential disadvantage to their proposed regulatory scheme is that it could stifle drug development.

“Allowing stool banks to continue to provide stool to physicians for treatment of CDI, even after a new drug is approved for that indication, may discourage investment in track 3 drugs to treat CDI and other conditions that could be treated by stool-based products,” they wrote.

They concluded that their proposed framework would be “relatively easy” for the FDA to implement, and could serve as “a useful starting point” for regulating other types of microbiota transplantation. – by Adam Leitenberger

Disclosures: This work was supported by the National Institute of Allergy and Infectious Disease.

Editor's note: This article was updated on Dec. 21 with clarifications from Hoffmann.