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Regulators Grapple With an Unorthodox Therapy

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Science  30 Aug 2013:
Vol. 341, Issue 6149, pp. 956
DOI: 10.1126/science.341.6149.956

As fecal transplants are becoming popular, governments wonder how to respond.

Patient's voice.

Catherine Duff spoke up at an FDA workshop in May.

CREDIT: COURTESY OF CATHERINE DUFF

Taking one person's stool and putting it into the gut of another may be simple enough—but regulating it is not. The rapid rise of fecal transplantation, coupled with pressure from enthusiastic patients and doctors, has regulators wondering how to respond. The procedure occupies an odd place somewhere between tissue transplants and "probiotic" therapies—infusions of beneficial bacteria—and its risks are unknown. Coming up with sensible regulation is even harder because unlike, say, a blood transfusion, anyone can perform a stool transplant at home.

So far, the European Medicines Agency has not stepped in to regulate fecal transplants; the only thing that doctors need to do is get the patient's informed consent and comply with a donor screening protocol. Australia, where gastroenterologist Thomas Borody has carried out thousands of fecal transplants (see main story, p. 954), has similarly relaxed regulations.

In the United States, by contrast, the Food and Drug Administration (FDA) recently asserted its authority over the procedure. At a workshop on 2 and 3 May in Bethesda, Maryland, FDA's Jay Slater said that transplants are considered "an unapproved new drug." That meant any transplant can be done only as part of an official clinical trial, and doctors need to file an Investigational New Drug (IND) application—which can take months. (The agency said it might make exceptions for life-threatening conditions on a case-by-case basis.)

An FDA spokesperson says that Slater's comments didn't represent a policy change. But many researchers interpreted them as a clampdown. Lawrence Brandt of the Montefiore Medical Center in New York City says that he rejected 25 patients suffering from recurrent Clostridium difficile infection—where the evidence that fecal transplants work is strongest—after hospital lawyers told him to stop.

Patients and doctors have long urged the agency not to interfere with the treatment. At the Bethesda workshop, FDA officials heard testimony from Catherine Duff, a 57-year-old former medical case manager from Carmel, Indiana, who related how a fecal transplant had cured her recurrent C. difficile infection—and saved her life. "Please, do something not only for me, but for all those around the country and everywhere," she implored the FDA. "Please do something quickly."

Duff's appearance "definitely left an impression on the FDA officials," says Alexander Khoruts, a gastroenterologist at the University of Minnesota Medical Center in Minneapolis who attended the meeting. In new guidelines issued on 18 July, the agency announced it would "exercise enforcement discretion" in the case of C. difficile—meaning that, if they meet certain conditions, doctors can perform fecal transplants without prior approval. An IND is still needed for all other diseases and for C. difficile therapy in infants. The new guidance is widely regarded as a stopgap measure that gives the agency time to develop more comprehensive regulations.

FDA's task might get easier if scientists can replace fecal transplants with standardized mixes of microbial strains grown in the lab, which are simpler and presumably less risky. On 29 July, FDA approved a phase II trial with such a cocktail, developed by a company called Rebiotix. But Canada's federal regulatory agency clamped down on a similar product. After an academic collaboration named RePOOPulate treated two C. difficile patients with a mixture of 33 stool-derived microbial strains, Health Canada ordered a halt to the procedure in 2011; it said the mix is a "synthetic" product for which drug approval is needed and gave the scientists a long list of criteria to meet.

"Actually, they are not unreasonable," says RePOOPulate project leader Elaine Petrof. "Health Canada realizes this technique is not going away, and they want to sort this out with us."

  • * Jop de Vrieze is a science writer in Amsterdam.

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