Regulatory Approach for Fecal Transplant Product Finalized in Abrupt Guidance Document

Posted 17 July 2013 | By Alexander Gaffney, RAC 

After deciding in June 2013 to begin fast-tracking fecal transplant procedures by scrapping an earlier requirement that would have mandated an approved Investigational New Drug (IND) application, the US Food and Drug Administration (FDA) had just released a new guidance document clarifying the enforcement approach it informally announced in June.


Fecal transplants are a relatively new innovation involving the transfer of either fecal matter or the bacteria found within fecal matter from a healthy patient to a sick one. Various published research has identified the procedure as being one that can fight off Clostridium difficile 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 Fecal Microbiota Transplants (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 - a problem FDA has been grappling with over the course of the last year.

At first, FDA said in May 2013 it would require the products to be administered under an approved IND, which is ordinarily required for pharmaceutical products seeking FDA approval. The agency said a current lack of regulation was potentially resulting in patients receiving dangerous therapies.

However, FMT advocates fought back against FDA, saying the new rules were onerous and costly, and would result in more patients resorting to do-it-yourself fecal transplants outside of medical facilities.

Abrupt Reversal

However, just a month after its initial announcement, FDA said it would resort to a compromise it has used in many other instances: While maintaining its authority to require the submission of an IND in some cases, it would resort of a policy of "enforcement discretion" under which it would allow most practitioners to continue to conduct FMT procedures without an approved IND.

"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."

That policy, announced informally in June, has now been made official under the new guidance document, Enforcement Policy Regarding Investigational New Drug Requirements; Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies, released on 18 July 2013.

Mirroring its earlier statements, FDA said it "intends to exercise this discretion provided that the treating physician obtains adequate informed consent from the patient or his or her legally authorized representative for the use of FMT products."

That informed consent form should, "at a minimum," include a statement that the FMT product is still investigational and involves assuming potential risks, FDA added.

A Stopgap Measure

FDA's regulatory enforcement discretion approach is not intended to be used over the long term, it 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 intends to exercise this discretion on an interim basis while we further consider the matter," it added in a Federal Register posting announcing the guidance.

The release of the guidance is relatively unusual in that it did not involve prior public participation, which FDA deemed unnecessary as it would have been neither "feasible [nor] appropriate" due to its urgency.

Voluntary Compliance Approach

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.

The stopgap measure may be intended to hold the fledgling therapeutic area over until approved therapies reach the market, the first of which may arrive soon. In late June 2013, FDA granted "fast track" status to Rebiotix's FMT suspension RBX2660, meaning the product could see an approval decision within six months.

The guidance only applies to FMT products intended to treat C. difficile, FDA added.

Comments on the guidance may be submitted at any time.

Guidance for Industry: Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to Standard Therapies

Federal Register Notice

FDA's June 2013 Notice on FMT

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