Enforcement Policy Regarding 
Investigational New Drug 
Requirements for Use of Fecal 
Microbiota for Transplantation to 
Treat Clostridioides difficile Infection 
Not Responsive to Standard Therapies 
 
 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
Additional copies of this guidance are available from the Office of Communication, Outreach 
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, 
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010 or email ocod@fda.hhs.gov, or 
from the Internet at https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-
regulatory-information-biologics/biologics-guidances. 
 
For questions on the content of this guidance, contact OCOD at the phone numbers or email 
address listed above. 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
November 2022  Contains Nonbinding Recommendations 
Table of Contents 
 
 
I.  INTRODUCTION ..................................................................................................................... 1 
II.  DISCUSSION AND ENFORCEMENT POLICY .................................................................. 2 
 
  i  Contains Nonbinding Recommendations 
Enforcement Policy Regarding Investigational New Drug 
Requirements for Use of Fecal Microbiota for Transplantation to 
Treat Clostridioides difficile Infection Not Responsive to Standard 
Therapies 
 
Guidance for Industry 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on FDA or 
the public.  You can use an alternative approach if it satisfies the requirements of the applicable 
statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible for 
this guidance as listed on the title page. 
 
 
I.  INTRODUCTION 
 
We, FDA, are informing members of the medical and scientific community and other interested 
persons of our policy regarding the investigational new drug application (IND) requirements for 
the use of fecal microbiota for transplantation (FMT) to treat Clostridioides difficile (C. difficile) 
 
infection not responding to standard therapies.1  At this time,FDA intends to exercise enforcement 
discretion with respect to such requirements under limited circumstances as described in section II 
of this guidance.  This policy does not apply to FMT that is obtained from a stool bank. 
 
A stool bank is defined, for the purpose of this guidance, as an establishment that collects, 
prepares, and stores FMT product for distribution to other establishments, health care providers, or 
other entities for use in patient therapy or clinical research.  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. 
 
In development of this policy FDA has considered input from stakeholders, including physicians, 
scientists, and patients concerned about sufficient access to FMT for patients with C. difficile 
infection not responding to standard therapies.  FDA has developed this policy to help facilitate 
access for such patients, while addressing and controlling the risks that centralized manufacturing 
in stool banks presents to individuals receiving such products. 
   
 
1 FMT administered to treat C. difficile infection meets the definition of a biological product, as defined in section 
351(i) of the Public Health Service (PHS) Act (42 U.S.C. 262(i)) and the definition of a drug within the meaning of 
section 201(g) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321(g)).  As a biological product, FMT 
administered to treat C. difficile infection is subject to the licensing requirements set forth in section 351 of the PHS 
Act (42 U.S.C. 262).  It is, however, exempt from these licensing requirements when administered pursuant to an IND 
and in compliance with the IND regulations set forth in 21 CFR Part 312.  (See 42 U.S.C. 262(a)(3)). 
 
  1  Contains Nonbinding Recommendations 
This guidance finalizes the draft guidance entitled Enforcement Policy Regarding Investigational 
New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium 
difficile Infection Not Responsive to Standard Therapies dated March 2016, and supersedes the 
guidance entitled Enforcement Policy Regarding Investigational New Drug Requirements for Use 
of Fecal Microbiota for Transplantation to Treat Clostridium difficile Infection Not Responsive to 
Standard Therapies dated July 2013 (July 2013 guidance). 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only as 
recommendations, unless specific regulatory or statutory requirements are cited.  The use of the 
word should in Agency guidances means that something is suggested or recommended, but not 
required. 
 
 
II.  DISCUSSION AND ENFORCEMENT POLICY 
 
Fecal microbiota collected from healthy individuals are being investigated for use in the treatment 
of C. difficile infection.  Published data suggest that the use of fecal microbiota to restore intestinal 
flora may be an effective therapy in the management of refractory C. difficile infection.   
 
In this guidance, we are revising the policy described in the July 2013 guidance.  Centralized 
manufacturing in stool banks presents safety concerns related to the number of patients that may be 
exposed to a particular donor and particular manufacturing practices.  These safety concerns 
include transmission of infectious agents.2  Therefore, at this time, FDA does not intend to extend 
enforcement discretion with respect to the IND requirements for distribution of FMT products 
  
obtained from stool banks.3,4 The sponsors compliance with the IND requirements5 in these 
situations will help to ensure that the stool donor and stool are appropriately qualified by screening 
and testing and that centralized processing of FMT adheres to appropriate current good 
manufacturing practice. 
   
 
2 For example, FDA issued a safety alert in March 2020 after becoming aware of patients who developed infections 
caused by enteropathogenic Escherichia coli (two patients) and Shigatoxin-producing E. coli (four patients) following 
receipt of an FMT product supplied by a stool bank.  As explained in the safety alert, FDA suspects the infections were 
due to transmission of these pathogenic organisms from the FMT product.  See Safety Alert Regarding Use of Fecal 
Microbiota for Transplantation and Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic 
Organisms (March 12, 2020); Update to March 12, 2020 Safety Alert Regarding Use of Fecal Microbiota for 
Transplantation and Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms (March 13, 
2020). 
3 The policy outlined in this guidance pertains to minimally processed fecal material obtained from donors to treat C. 
difficile infection not responding to standard therapies.  Examples of minimal processing include, sieving, 
centrifugation, buffer exchange, addition of cryoprotectants, lyophilization and packaging.  Some examples of 
processing procedures that would be considered beyond minimal processing include amplification or reduction of 
certain enteric species, selection of specific groups of bacteria, or any other intended modification of the microbial 
composition of the fecal preparations.  
4 If the FMT is provided by a contract manufacturer, this entity should hold an IND or ship to a sponsor with an active 
IND.  In lieu of providing manufacturing information to the IND sponsor, the contract manufacturing facility may 
provide a letter, permitting the IND sponsor to cross-reference a master file with this information. 
5 A sponsor may request FDA to waive applicable requirements under 21 CFR Part 312.  The required content and 
process for submitting a waiver request are described at 21 CFR 312.10. 
  2  Contains Nonbinding Recommendations 
In light of the considerations described above, at this time, we intend to exercise enforcement 
discretion with respect to applicable IND requirements when the FMT product is not obtained from 
a stool bank and where: 
 
1.  The licensed health care provider treating the patient obtains appropriate consent 
from the patient or his or her legally authorized representative for the use of FMT 
product.  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 the products 
reasonably foreseeable risks.6 
 
2.  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 to treat his or her patient. 
 
3.  The use of the FMT product does not raise reported safety concerns or potential 
significant safety concerns (e.g., concerns regarding inappropriate storage or 
handling, or concerns regarding administration of product collected without 
appropriate screening or testing). 
 
FDA will continue to work with sponsors who intend to submit INDs for use of FMT to treat C. 
difficile infection not responding to standard therapies.  The Agency will also continue to evaluate 
its policies concerning the use of such FMT products as scientific evidence in this area evolves.  
 
This enforcement policy does not extend to other uses of FMT.  Data related to the use and study of 
FMT to treat diseases or conditions other than C. difficile infection not responding to standard 
therapies are more limited, and study of FMT for these other uses is not included in this 
enforcement policy. 
 
We encourage all health care providers administering FMT products to report suspected adverse 
events to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. 
 
6 FDAs regulations require that, in seeking informed consent, an identification of any procedures that are experimental 
and a description of any reasonably foreseeable risks, among other things, be provided to each subject or the subjects 
legally authorized representative.  21 CFR 50.25(a)(1)-(2). 
  3