Fecal bacteriotherapy (FBT), a procedure hailed by many gastroenterology researchers as a less costly and equally efficacious alternative to treating C. difficile infection (CDI) has been somewhat derailed by the Food and Drug Administration (FDA). The FDA has recently announced that fecal bacteria is a biologic product not approved by the agency for any therapeutic use. Therefore, physicians and researchers wanting to perform the procedure for any indication, including CDI, must file an Emergency Use Investigational New Drug Application (IND).
The therapy, which involves infusing a watered-down bit of a donor's feces into the patient's digestive tract through a tube into the colon, produces a rapid response and very high success rate (84% to 100%) in treating recurrent CDI. Symptoms usually resolve within 24 to 48 hours, even in patients with long-term, severe disease. Relative to the multiple courses of expensive antibiotic therapy and the cost of care associated with severe C. difficile-associated disease (CDAD), FBT is much less expensive—in part because there are no commercial costs related to the manufacture or marketing of the bacterial flora.
The FDA’s decision to require an IND before performing the procedure was apparently confirmed at a public workshop held in May 2013, although no transcript from the meeting has been posted to the FDA website.
The underlying reason given by the agency for this new regulation is the lack of evidence. Yet, the evidence for FBT is burgeoning. Numerous smaller studies and systematic reviews describing positive results have been published over the past 30 years; this year, the first results from a randomized clinical trial comparing FBT to vancomycin were published. The study had planned to enroll a total of 120 patients with recurrent CDI after at least 1 course of current care vancomycin. The study was halted early after an interim analysis of the first 43 patients showed a significant benefit of FBT over vancomycin, and a very high rate of CDAD recurrence in patients treated with vancomycin.
Patient safety is a key priority at the FDA. However, it’s unfortunate that the agency decided on such an onerous way to “protect” patients—especially in the light of evidence showing that the procedure is safe, effective, and less costly than existing pharmaceutical options. The FDA has stated that they will try to streamline the IND process in case of an “emergency”; however, as the process has 10 different steps and requires input from busy physicians and researchers, it is likely that patients who might benefit from the procedure will find it more difficult to do so. Placing stringent requirements on staff to produce and manage the IND process may also increase the cost burden of the procedure, as well.
It will be interesting to see how this plays out. The FDA has a mission to ensure the safety, efficacy, and security of drugs, biologics, and devices. But there is also a documented medical need for less conventional, evidence-based treatments that are more effective than traditionally approved therapies and that can be administered in a timely and cost-effective manner.
The FDA is currently implementing a transparency initiative as a way to keep interested stakeholders aware and apprised of the agency’s policies. Perhaps this new initiative will create an opportunity for the agency to keep researchers, consumers, and industry apprised of the agency’s plans and progress to reclassify fecal bacteria. And even more importantly, let’s hope that the FDA finds a way to expedite the process for approving FBT, so patients who need it can get it—without getting mired in red tape.