FDA slaps regs on fecal transplants

When Dr. Michael Edmond learned that the Food and Drug Administration had tightened its regulations governing fecal transplants, he promptly canceled 10 scheduled appointments for the procedure.

Most of those were for elderly patients who had been on the antibiotic vancomycin for weeks or even months to stave off the symptoms of their Clostridium difficile infections, said Edmond, a professor of internal medicine in the division of infectious diseases at Virginia Commonwealth University, Richmond.

“These patients are very, very sick and the antibiotic therapies we have for them are not really effective,” he said. “They are stuck.”

For physicians who perform fecal transplants, an increasingly relied-upon treatment for patients with serious, recurrent cases of C. diff, the days of flying under the radar of federal oversight are over.

The FDA recently announced that the use of “fecal microbiota for transplantation” meets its definition of a biologic product, meaning doctors who want to perform transplants must submit an investigational new drug application, or an IND.

The move rankled some physicians, including Edmond, who worry that the additional paperwork, 30-day waiting period and other requirements of an IND could hinder access to the procedure, which uses donor feces to repopulate good bacteria in the guts of patients with C. diff.

“It's unfortunate for patients because it puts up another barrier to get a procedure that they really need,” Edmond said. “It's going to mean a mountain of paperwork, writing protocols, writing exclusion and inclusion criteria, and explaining what I'll do if someone has a side effect. I just can't do it.”

Rates of C. diff have soared to “historically high levels,” according to data from the Centers for Disease Control and Prevention, even as providers have made gains in controlling other types of healthcare-associated infections. C. diff is linked to 14,000 deaths annually, according to the CDC. Fecal transplants have been shown to be effective in treating stubborn cases of the bug, with many physicians reporting success rates of 80% to 95%.

And in January, the New England Journal of Medicine published the results of the first randomized controlled trial of fecal transplants as a treatment for C. diff. That study, conducted in the Netherlands, found much higher success rates for fecal transplants than for the antibiotic vancomycin. The findings were so striking, in fact, that the study was halted because of concerns that it was unethical to prevent patients in the vancomycin group from receiving transplants.

After canceling all of his upcoming fecal transplant appointments, Edmond advised his patients that they could still use at-home enema kits, a choice he predicted some would opt for if they can't find a physician willing to do it. “It will still happen, just not in a controlled environment,” Edmond said.

But other physicians welcomed the FDA's oversight, arguing it would lead to evidence-based standards and greater protections for patients.

“I looked at it as a very positive thing,” said Dr. Charles Posternack, chief medical officer at 394-bed Boca Raton (Fla.) Regional Hospital, which has performed fecal transplants since late 2012. “The FDA recognizes that this treatment is important and, in many cases, life-saving for patients. They just want it controlled."

Posternack bristled at suggestions that the FDA's IND requirements were onerous and would put undo burden on physicians. The process does take some effort, he said, but he argued that it quickly becomes second nature. He also said the FDA's expanded role would foster collaboration and evidence sharing among sites that perform the procedure.

“We plan on fulfilling all of the requirements, getting our investigators credentialed and becoming a research center for this treatment,” Posternack added.

The FDA contended that it has always had authority over the procedure and that it previously advised inquiring physicians of their need for an IND. But after a two-day workshop on fecal transplants, held this month, the agency solidified its requirements, said Curtis Allen, an FDA spokesman.

The FDA offers guidance to physicians on how to complete the application, Allen said, adding that the agency can also authorize emergency INDs, in some cases.

“In an emergency situation, the request to use fecal microbiota for transplantation (FMT) may be made via telephone or other rapid means of communication, and authorization may be given by the FDA official over the telephone,” Allen said in an e-mail. “In these situations, known as emergency INDs, treatment may begin prior to FDA's receipt of the written IND submission that is to follow the initial emergency request.”

Dr. Paul Sax, clinical director of the division of infectious diseases at Brigham and Women's Hospital, Boston, said he wasn't surprised to hear of the FDA's newly clarified stance, given that the agency's primary mandate is to ensure patient safety. But he did call the news ironic, because fecal transplants have been used extensively without an IND for some time, with very high success rates.

“I'm not critical of their decision because we want something like this to be done safely and appropriately,” Sax said.“I'm just hoping it won't be an impediment.”

Follow Maureen McKinney on Twitter: @MHMMcKinney