The US Food and Drug Administration (FDA) on Monday announced new draft guidance that aims to further assure that patients infected with the bacterium Clostridium difficile and not responding to standard therapies can access poop transplants, also known as fecal microbiota for transplantation (FMT).

FDA considers FMT an investigational new drug (IND), which requires physicians and scientists to file an IND application if they intend to use the treatment for clinical practice or research. However, FDA has issued guidance stating that FMT may be used to treat C. difficile infection not responsive to standard therapies outside of a clinical trial. 

New Guidance

The latest draft guidance offers new notice that FDA intends to exercise enforcement discretion regarding the IND requirements for the use of FMT to treat C. difficile infection.

As far as what FDA wants to discuss on this new draft guidance, the agency says it’s requesting comments on which IND requirements are appropriate to waive.

“In particular, FDA is requesting comments on the requirement for institutional review board review of the use of FMT to treat patients with C. difficile infection not responding to standard therapies when the FMT is provided by a stool bank,” FDA says.

Background

The draft guidance comes as over the past few years, FMT, which basically involves the transfer of a healthy donor stool to the bowel of a patient infected with C. difficile, has emerged as an effective means to treat recurrent forms of the bacterial infections, according to a study in the Journal of Law and Biosciences.

Rachel Sachs, an academic fellow at Harvard University’s Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics, and an author of that study, explained to Focus that previously FDA said it would regulate FMT like a biologic, but that the decentralized, hospital-based model of FMT envisioned in this new draft guidance more closely resembles the agency's models for regulating tissue or cord blood products.

Two companies – Rebiotix and Seres Therapeutics – have been granted orphan drug designations for their INDs as FMT treatments for recurrent C. difficile infections, which affect between 85,000 and 110,000 people in the US annually.

And Sachs said she’s under the assumption that once a company gets FDA approval for their FMT product, FDA will revoke its enforcement discretion included in this new guidance.

Guidance Details

FDA said Monday it intends to use this discretion for waiving certain IND requirements, provided that:

• The licensed health care provider treating the patient obtains consent from the patient or his or her legally authorized representative for the use of FMT products. The consent should include, at a minimum, a statement that the use of FMT products to treat C. difficile is investigational and a discussion of its reasonably foreseeable risks;
• The FMT product is not obtained from a stool bank; and
• The stool donor and stool are qualified by screening and testing performed under the direction of the licensed health care provider for the purpose of providing the FMT product for treatment of the patient.

And FDA makes clear that an establishment that collects or prepares FMT products “solely under the direction of licensed health care providers for the purpose of treating their patients (e.g., a hospital laboratory) is not considered to be a stool bank under this guidance.”

Sachs co-authored her article with Carolyn Edelstein, director of policy and global partnerships at OpenBiome, a nonprofit stool bank that sells FMT capsules (recommended dose of 30 capsules plus a safety test capsule costs $535, or stool preparations for delivery by colonoscopy, enema, and EGD/naso-enteric tube are $385 each) after conducting first-in-human evaluations (N=4) and a randomized dose-finding study (N=17).

Edelstein told Focus that the draft “suggests that the FDA is seeking to set up a more tailored regulatory scheme, one that considers stool banking separately from small-scale directed donation. We are in favor of seeing stool banking receive more regulatory oversight. We plan to answer the agency's request for comments on the elements of a regulatory framework that would lend this oversight to the practice of stool banking without unduly burdening the physicians and healthcare facilities using banked material, and by extension, unduly limiting access to the treatment for their patients.” 

FDA also explains that there were “difficulties in interpretation” with previous draft guidance, particularly around the provision that the donor be known either to the patient or to the treating licensed health care provider, noting “the revised approach more accurately reflects our intent to mitigate risk, based on the number of patients exposed to a particular donor or manufacturing practice rather than the risk inherent from any one donor.”

But as new FMTs are likely to hit the market as orphan drugs, the bigger issue at play could be associated with cost. Sachs noted that any FDA-approved treatment, particularly since it’s an orphan product, could be expensive (upwards of thousands of dollars for treatment).

Federal Register Notice