The US Food and Drug Administration (FDA) has found itself mired in - quite literally - a crappy situation. In February 2013, the agency announced that it would reach out to the public in an attempt to determine how it should go about regulating fecal microbiota for transplantation (FMT), a treatment that many doctors now say can be useful in eradicating C. Difficile. But after FDA proposed to regulate the products as biologics and require them to obtain investigational new drug (IND) status before being used, FMT advocates fired back, and now FDA has indicated that it will reconsider its regulatory approach.
Fecal transplants might sound gross, but various published research has identified the procedure as being one that can fight off C. diff infections by introducing so-called "good bacteria" back into a person's body. The idea is to overload the gastrointestinal tract with enough of the good bacteria to overwhelm the C. diff, thereby ending the infection.
One device, known affectionately as either the "RoboGut" or the "RePoopulation Station," is essentially a small manufacturing facility that takes a selected 33 strains of healthy fecal microbiota which are then reproduced in a mixture for eventual transplantation during a colonoscopy procedure.
By standardizing the procedure, the researchers said they hoped to reduce the variability that now exists when FMTs are conducted and reduce the time between a patient having a need for the transplant and it occurring. At present, donors need to be found and screened, and patients aren't necessarily sure if they're getting the bacteria they need.
As Regulatory Focus explained in January 2013, the uniform product would allow for much higher assurances of quality, safety and efficacy. But that will eventually depend on approval by FDA regulators. This, too, poses some interesting problems, and ones not likely to be answered until the manufacturers determine how the product is to be marketed.
If the device itself is sold as a method to manufacture the mixture on site, it could be a combination device with a primary mode of action that is biologically based, potentially requiring review by both the Centers for Biologic Evaluation and Research (CBER) and Devices and Radiological Health (CDRH). If it is sold on its own, it might only require regulatory review by the former, likely falling under human cell tissue and tissue-based products (HCT/P) regulations.
INDs for FMTs?
In advance of a May 2013 meeting held by FDA to discuss FMT, the administration seemed to agree with the assessment that regulating these products would be difficult, but focused more on the clinical aspects of the regulation and less on the quality manufacturing aspects.
The meeting, however, revealed some rather surprising news: FDA would require physicians who wished to conduct the procedure to submit an IND, an application most often associated with the start of a clinical trial.
The problem, regulators told MedPage Today, was that an absence of regulation in the area could subject patients to an unproven and potentially dangerous cocktail of microbiota that could do more harm than good.
But to doctors and advocates of FMT procedures, FDA's attempt to regulate the fledgling industry would stymie or even destroy it, harming patients even more by denying them access to a potentially curative procedure.
Their main complaint relates to the cost of putting together and filing an IND, which is both time consuming and expensive, and the costs and difficulties associated with actually running a clinical trial, which requires the use of an institutional review board (IRB) and adherence to a wide range of regulations.
The requirement, in other words, decreases the procedure's availability, increases its cost, and increases the hurdles for patients to obtain the treatment. Some industry analysts said the requirement could have the opposite effect as intended, with desperate patients conducting do-it-yourself fecal transplants using whatever product they could get their hands on, potentially subjecting them to other diseases.
FDA Backs Off
Now FDA says it is backing off its previous proposal, adopting a now-familiar tactic in which it maintains that it has the authority to regulate FMT, but will instead exercise "regulatory discretion" when it comes to the procedures.
"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," FDA explained. "The agency acknowledges these concerns and intends to exercise enforcement discretion regarding the IND requirements for the use of FMT to treat C. difficile infection not responding to standard therapies provided the treating physician obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products."
This is not, however, to say FDA will require nothing from sponsors of the procedure. They will, "at a minimum," be required to obtain informed consent from patients participating in the procedure, including an explicit acknowledgement that FMT is an investigational procedure and carries with it potential risks.
Neither is the regulatory enforcement discretion approach intended to be used over the long term, FDA said. Instead, it is meant to be a stopgap measure while it "develops appropriate policies for the study and use of FMT products under [an] IND." FDA added that it intends to issue a guidance document for industry regarding the limits of its enforcement discretion policy.
For now, however, sponsors are still "strongly encouraged" to comply with the agency's IND regulations, FDA said. "[FDA] stands ready to work with sponsors who are interested in conducting clinical trials," it added.
FDA: IND Requirements for FMT