The agency’s regulation of potentially infectious material is fraught with legal and historical peculiarities. For instance, the FDA does not regulate donated breast milk, although it warns on its website that milk can transmit infectious diseases, like HIV, and should be screened. Nor does it require manufacturers of dietary supplements, which can include probiotics containing live bacteria, to seek the agency’s approval. (The FDA’s Center for Biologics Evaluation and Research does have jurisdiction, however, over probiotics that are intended to prevent, treat, or cure disease.)
In theory, fecal matter could be regulated as a human tissue, like lungs or livers used for transplantation. Smith, Alm, and a gastroenterologist named Colleen Kelly made the case for this approach in February in an article in Nature, noting that the “human gut microbiome has been described as a ‘virtual organ.’” And several experts agreed: “Of all the categories the FDA has for regulation, tissue is the one that makes the most sense,” said Rob Knight of the University of Colorado, Boulder. “Someone’s body made that liver,” he added, and the same could be said of stool for transplant. Formally, though, the category of “human cells, tissues, or cellular or tissue-based products,” as the FDA defines it, excludes “secreted or extracted human products.” (This means that milk is excluded, though for some reason semen is not.) It’s possible that a senior official within the executive branch could redefine stool as a tissue, but “we’re really uncertain how these decisions are made,” James Burgess of OpenBiome said. The FDA said it “cannot make predictions regarding the future regulation” of therapies using fecal transplantation.
Someday, a commercial product may replace stool, making some of these issues less fraught. “Initially our whole plan was that this would be a bridge,” Burgess said. “We thought it was crazy [that] people weren’t getting treated.” Work conducted with material from OpenBiome might also aid efforts to figure out the “active ingredients” for treating C. diff, thus guiding efforts to create a synthetic substitute. That is a “huge research priority for us,” Alm said. If such a product became available, it’s even possible that OpenBiome would alter its mission to focus more heavily on research.
In the meantime, though, the group is making nice with the FDA. It is working to broker a compromise regarding the agency’s investigational new drug requirements. OpenBiome has agreed to help four of its providers perform fecal transplants as part of an IND study. This multicenter, phase-two trial will track up to 200 patients with recurrent C. diff for a year after they receive the procedure. Regulators are “rightly concerned” about unregulated transplants, Smith said, but “they see we can help drive rigorous data collection … They will get more good data working with us than they would have otherwise.”