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FDA's Frozen Poop Problem

Posted 24 April 2014 | By Alexander Gaffney, RAC

Researchers have announced a breakthrough that may make it even easier to treat patients infected with Clostridium difficile (C. diff) using a novel but controversial technique involving fecal matter. And while the news is fantastic for patients, it presents challenges for the US Food and Drug Administration's (FDA) current regulatory policies.


The technical name for those poo-based products is fecal microbiota- the bacteria found within a person's fecal matter. In recent years, researchers have begun to transplant those bacteria into patients afflicted with C. diff, a hardy infection.

The theory behind the fecal microbiota transplant (FMT) procedure, as it is called, 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.

But to date, there have been two main problems: One related to production, and the other of regulation.

Regulatory Hurdles

FDA's response to FMT treatments has been either inconsistent or evolving, depending on your interpretation of the issue.

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 an application used to begin or continue clinical testing in humans, and are meant to show that a product meets baseline levels of safety.

FDA said a lack of regulation was resulting in patients receiving potentially dangerous forms of FMT, such as donations from those with different types of diseases.

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 medical facilities.

That pushback resulted in FDA reversing its decision in less than a month. 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 a 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.

Production Challenges

As we said earlier, the other challenge has been one of production. As fecal microbiota are literally obtained from fecal matter, finding willing donors can be difficult.

Beyond supply, the other challenges have been related to standardization and transportation. Because the microbiota of each donor is different, it has been difficult to ensure a standardized benefit-risk calculus. As FDA said, the introduction of dangerous bacteria could be particularly problematic for patients afflicted with C. diff.

Several entities have popped up to try and solve the standardization problem. 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.

Another product is Rebiotix's RBX2660, a microbiota suspension now seeking FDA approval under its fast-track program and undergoing phase II clinical testing. That product could result in a massive change in how FDA regulates FMT products if it is eventually approved, as FDA would no longer need to-though it could-continue its enforcement discretion policy.

Challenge: Storage

In the meantime, though, there's been another challenge: storage. Bacteria don't exactly thrive outside of their usual host environments, and fecal microbiota are no exception.

But researchers at Massachusetts General Hospital recently decided to put a question to the test: Could the bacteria be frozen and used at a later date?

The answer, published in the journal Clinical Infectious Diseases, is yes. The researchers said that prescreened, frozen fecal material "was as successful in curing recurrent C difficile infection as was the use of fresh material reported in previous studies of what is called FMT."

"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.

Regulatory Stumbling Block

That advancement could allow researchers and healthcare providers to "bank" treatments from donors, making it easier to treat patients on an as-needed basis. However, that will take the permission of FDA.

As we noted earlier, FDA's current enforcement policy contains an unusual requirement: the FMT product must be "obtained from a donor known to either the patient or the licensed health care provider treating the patient."

This means that even if one facility is able to obtain a large quantity of high-quality, screened donors and store their fecal donations in a frozen state, another doctor would be unable to use that product under FDA's current enforcement discretion policy.


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