Investigational New Drug Protocol
The US Food and Drug Administration (FDA) has classified human stool as a biological agent and determined that its use in fecal microbiota transplantation (FMT) therapy and other research should be regulated to ensure patient safety.
To use FMT to treat recurrent Clostridium difficile infection (RCDI), an investigational new drug (IND) permit is not required, but is strongly encouraged and may ultimately be required.
To use FMT for research or to treat any condition other than RCDI, an IND permit is required.
The FDA has released clarifying guidance in March 2016 and the DRAFT of 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 (PDF) is available for review. This guidance document has not been finalized by the FDA and is intended for comment purposes only.
IDSA provides comments for the draft of Guidance for Industry regarding the enforcement policy of IND requirements for use of FMT to treat RCDI.
Further Information and Rationale for “known donor”:
I. The donor most commonly “known” to the recipient is the spouse or significant/intimate partner which minimizes the likelihood of transmitting an occult pathogen with the stool sample.
II. The microbiome in health changes as we age. Most RCDI patients are Medicare age while commercial donors are young adults. It makes theoretical sense to rebuild the dysbiotic microbiome with components (bacteria) collected from a healthy donor of roughly the same age as the recipient.
III. Out-of-pocket costs for the donor and recipient will depend on insurance coverage design and will vary depending on whether a sample is obtained from a “known” donor versus a “universal donor” source. Assuming the “known” donor’s insurance covers the costs of screening, the cost associated would be the out-of-pocket co-insurance/copay rate versus the cost of buying commercial stool. This is a case-by-case issue.
IV. There may be cases where a suitable stool sample may not be obtainable from a donor “known” to the patient or physician. As well, there may be cases where obtaining a suitable sample from a donor “known” to the patient/physician may be too time consuming given the severity of the case. In these situations, use of a suitable sample from a “universal donor” source may be warranted. The physician should ensure that the “universal donor” source employs rigorous screening and testing standards.
FDA Forms and Documentation
- Introductory Statement: FMT Treatment for Patients who Experience RCDI (PDF)
- Treatment Protocol: FMT by NasoDuodenal Tube for Patients who Experience RCDI (PDF)
- Treatment Protocol: FMT by Enema for Patients with RCDI (PDF)
- Informed Consent Template (PDF)
- Guidance on Completing FDA Form 1571 (PDF)
- FDA Form 1571 for FMT (PDF)
- FDA Form 1571 Instructions (PDF)
- FDA Form 1572 (PDF)
- FDA Form 1572 Instructions (PDF)
- FDA Form 3674 (PDF) ;
- FDA Form 3674 Information Supplement (PDF)
"Fecal Microbiota Transplantation: A Practical Update for the Infectious Disease Specialist," Clinical Infectious Diseases, published 2013.
"Investigational New Drug forms and Instructions," FDA.gov, updated 2010.
United States Fecal Microbiota Transplantation Provider Sites, Google Maps, updated 2014