Only a month after requiring a restrictive new-drug permit to treat Clostridium difficile infection with fecal transplants, the Food and Drug Administration has changed course.
Citing public pressure, the agency announced June 17 that it "intends to exercise enforcement discretion" regarding the investigational new drug (IND) requirements while the agency develops appropriate policies for the use of fecal microbiota for transplantation (FMT) products under IND.
Dr. David T. Rubin
The change applies only to those using FMT to treat C. difficile infection that fails to respond to standard therapy. Those using FMT for other indications or for research purposes must abide by the IND requirements.
The FDA first announced the biologic designation following a 2-day public workshop in May, stating that the intent of the IND requirement was to ensure safe, effective, and data-driven use of FMT, which is used primarily to treat recurrent C. difficile infection.
"During that workshop, and in subsequent communications, physicians and scientists have expressed concern to FDA that FMT is not appropriate for study under FDA’s investigational new drug application regulations," the latest FDA statement noted. "Some health care providers have stated that applying IND requirements will make FMT unavailable and have suggested that an alternative regulatory approach is needed to ensure the widespread availability of FMT for individuals with C. difficile infection unresponsive to standard therapies."
Treating physicians are strongly encouraged to comply with the IND regulation and must continue to obtain informed consent for the use of FMT products, including, at minimum, information about the investigational status of the products and a discussion of the potential risks associated with their use.
Guidance will be issued regarding the agency’s intentions with respect to "exercising enforcement discretion," according to the FDA statement.
"A lot of people were upset about the IND requirement because it was a barrier to the most effective treatment available for C. difficile infection," Dr. David T. Rubin said in an interview.
Although Dr. Rubin’s area of focus is ulcerative colitis – he developed a protocol for using FMT in that disease and last month obtained an IND permit for a phase I study of its safety and feasibility in ulcerative colitis patients – he explained that C. difficile infection is the condition for which the most data exist.
People who have suffered for years are experiencing significant improvement and even cure with this treatment, said Dr. Rubin, professor of medicine and codirector of the inflammatory bowel disease center at the University of Chicago.
"C. difficile is where it seems to have its best efficacy, and it looks very safe," he said. "Even one dose of the treatment has a greater than 90% success rate."
Because obtaining an IND permit is a rigorous process – it took Dr. Rubin 2 years to obtain his permit – those using FMT for their patients were understandably concerned that patient access to treatment would be hampered. It’s one thing for a pharmaceutical company making an investment in a future salable product to jump through those kind of hoops, he explained, but it’s another entirely for a private physician who wants to offer patients the best available treatment.
The FDA’s decision is one that considers the importance of FMT for the treatment of patients with recurrent C. difficile infection while at the same time working to ensure patient safety and promote high-quality research, he said.
"There is still a whole lot we don’t know about FMT," he added.
Dr. Rubin had no relevant financial disclosures.