As Frozen Poop Pills Shown to be Effective in Study, FDA Policy in the Spotlight

Regulatory NewsRegulatory News
| 13 October 2014 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) has a frozen poop problem, and it's getting messier with time.


As Focus has explained in the past, FDA has been grappling with how to regulate an emerging medical procedure known as fecal microbiota transplantation (FMT) for several years. The procedure involves the transplantation of select fecal matter from one patient into another. While it may sound unusual, if not unsettling, emerging data show the procedure has been markedly successful at treating patients infected with Clostridium difficile (C. diff), a hardy infection.

The theory behind the FMT procedure is that by overloading the "bad" C. diff bacteria with the selected "good" bacteria, the infection can be overloaded, thereby effectively curing the patient of his or her C. diff infection.

Regulatory History

FDA, meanwhile, has found it difficult to establish a consistent regulatory approach for FMT. Because the process involves the donation of biological material from one patient, as well as the transplant of that material into a second patient, regulators have expressed concerns that patients might be exposed to blood-borne diseases like hepatitis C.

Accordingly, in May 2013, FDA said it would require FMT products to be administered under an approved Investigational New Drug application (IND), which is required for biological products seeking FDA approval. More practically, they're also used to begin or continue clinical testing in humans, and are meant to show that a product meets baseline levels of safety.

FMT advocates immediately cried foul, telling FDA that the new rules were onerous and costly, and would result in more patients resorting to do-it-yourself fecal transplants outside medical facilities.

That pushback resulted in FDA reversing its decision less than a month later. In a June 2013 announcement, FDA said it would institute a compromise of sorts, one built on a familiar concept known as "regulatory enforcement discretion."

FDA would maintain that it has the authority to regulate FMT products, but would allow more practitioners to conduct FMT procedures without an approved IND.

Then, in February 2014, FDA provided further clarification, describing a three-part set of conditions which, if met, would allow an FMT treatment to bypass the IND process. Those criteria are:

  1. Informed consent is obtained from the patient or his or her legally authorized representative.
  2. The FMT product is obtained from a donor known to either the patient or the licensed health care provider treating the patient.
  3. The stool donor and stool are screened and tested for the specific purpose of providing the product to the specific patient.

Failure to meet any of those standards will require the use of an IND, FDA said. In addition, FDA's policy does not apply to any other uses of FMT beyond C. diff. Some doctors have floated the idea that the FMT approach may also be useful for patients with Irritable Bowel Syndrome (IBS).

Some advocates have criticized the second of the three criteria, saying that being required to know the donor of the FMT bacteria could stymie attempts to standardize the treatments, and will otherwise make it more difficult to obtain the fecal bacteria used in the procedures and make it more likely that patients will result to DIY methods.

A New Product….

Why does this matter? Because FDA's policy is largely built upon the idea that FMT procedures involve a one-to-one transfer of biological material. One person, identified as a suitable donor and known to the patient or provider, donates fecal microbiota to a patient with C. diff.

But increasingly, this isn't how FMT is actually being done. Some companies and researchers are now trying to industrialize the FMT process, isolating the bacteria that are best suited to resolve a C. diff infection and ensuring that the product has a longer shelf life.

To the latter point in particular, researchers have been studying the use of frozen FMT donations—literally frozen poop pills—to treat patients. Their hope is that the freezer-stable pills could be kept on-hand for when they are needed, allowing a single donor to have a much broader impact.

Studies have previously indicated promise for these treatments. Most notably, an April 2014 study in the journal Clinical Infectious Diseases found the pills to be "as successful in curing recurrent C. difficile infection as was the use of fresh material."

"We found that delivery of a frozen, stored inoculum through a nasogastric tube is safe, acceptable to patients and as successful as delivery by colonoscopy - which requires a preparatory 'clean out,' sedation or anesthesia, and is quite costly," said Elizabeth Hohmann, senior author of the report, in a statement.

… New Data

Now additional data is supporting Hohmann's claims.

In a study released on 11 October 2014, research published in the Journal of the American Medical Association (JAMA) found that treating patients with C. diff with an "oral administration of frozen encapsulated fecal material from unrelated donors" was successful in resolving diarrhea in 90% of patients (n=20).

Best of all, "No serious adverse events attributed to FMT were observed," the study authors noted.

And beyond safety, the frozen poop pills have a plethora of other benefits, the study's authors contend:

"If reproduced in future studies with active controls, these results may help make FMT accessible to a wider population of patients, in addition to potentially making the procedure safer," the study authors said. "The use of frozen inocula allows for screening of donors in advance. Furthermore, storage of frozen material allows retesting of donors for possible incubating viral infections prior to administration. The use of capsules obviates the need for invasive procedures for administration, further increasing the safety of FMT by avoiding procedure-associated complications and significantly reducing cost," the authors write."

… Old Regulatory Hurdles

That's all well and good, but there's just one problem: FDA's current FMT policies don't allow for the widespread, easy use of frozen, orally-administered FMT.

In order to be exempt from FDA's IND requirements for FMT, a product must meet the following criteria:

  1. Informed consent is obtained from the patient or his or her legally authorized representative.
  2. The FMT product is obtained from a donor known to either the patient or the licensed health care provider treating the patient.
  3. The stool donor and stool are screened and tested for the specific purpose of providing the product to the specific patient.

While a frozen FMT product would likely meet the first and third criteria, the mass production of frozen poop pills would likely cause it to fail the second criteria, meaning all such products would need to be registered with FDA under an active IND—a significant hurdle for some research to clear due to the time and cost.

And without an easy way to distribute the pills, doctors will be forced to rely on existing methods of transplantation, which involve the use of tubes to administer the fecal microbiota.

While Hohmann and colleagues were able to operate their study under an approved IND, one can only wonder if other doctors will have the means (or time) to do so in the face of mounting consumer demand for the procedure.

And as for whether or not FDA will consider relaxing its policies to allow for great use of frozen FMT products, well, consider that question on ice for now.


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