Human Microbes

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WARNING LETTER

Warning Letter #CBER-24-672740

Date: February 09, 202

Dear Mr. Harrop:

This is to advise you that the United States Food and Drug Administration (FDA) has reviewed your website at www.humanmicrobes.org in February 2024, which contains instructions on how to buy fecal microbiota for transplantation (FMT) (hereinafter, “your products”). Your website indicates that you are offering for sale (in the United States, Canada, and other parts of the world) FMT in various forms (e.g., capsules, enemas, and infusions) for the treatment or prevention of various diseases or conditions. For example, your website states the following:

• “FMT is a lifesaving treatment for the deadly gut infection Clostridium Difficile (C. Diff) and has shown promising results in clinical trials for many other conditions [1], such as IBS (irritable bowel syndrome), IBD (inflammatory bowel disease), Parkinson’s disease, fibromyalgia, chronic fatigue syndrome (CFS), multiple sclerosis, autism, diabetes, and mental health disorders like depression, anxiety, and bipolar.”
• “FMT may also have potential applications in the treatment of obesity, autoimmunity, cardiovascular disease, cancer, and more.”
• “FMT is also a treatment option to attenuate adverse effects associated with antibiotic use.”

Additionally, your YouTube channel (https://www.youtube.com/watch?v=jPRg-_voHXQ) has a video titled, “We want your poop” that contains the following statements:

• “FMTs offer a potential new treatment option for a long list of conditions…including irritable bowel syndrome, obesity and even mental disorders.”
• Refers to a patient “cured her bipolar disorder after receiving an FMT”

Because these statements indicate that your products are intended for use in the mitigation, treatment, or prevention of disease, they are drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. § 321(g)(1)(B)]. Your products are also “new drugs” under section 201(p) of the FD&C Act [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective (GRASE) for their labeled uses. Additionally, your products are biological products as defined in section 351(i) of the Public Health Service Act (PHS Act) [42 U.S.C. § 262(i)] because they are applicable to the prevention, treatment, or cure of a disease or condition of human beings.¹

Please be advised that to lawfully market a drug that is also a biological product, a valid biologics license application (BLA) must be in effect [42 U.S.C. § 262(a)]. Such licenses are issued only after a demonstration that the product is safe, pure, and potent. A biological product for which a BLA has been approved under 42 U.S.C. § 262(a) is not required to have an approved application under section 505 of the FD&C Act [21 U.S.C. § 355; 42 U.S.C. § 262(j)]. Otherwise, with certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in 21 U.S.C. § 355(a). While in the development stage, such products may be distributed for clinical use in humans only if the sponsor has an investigational new drug application (IND) in effect as specified by FDA regulations [21 U.S.C. § 355(i); 42 U.S.C. § 262(a)(3); 21 CFR Part 312]. Your products are not the subject of an approved BLA or an approved application under 21 U.S.C. § 355. In addition, there is no IND in effect for their use. Therefore, your products are both unapproved new drugs and unlicensed biological products. Furthermore, based on the statements on your website, you cause the introduction or delivery for introduction into interstate commerce of your products in violation of the FD&C Act [21 U.S.C. § 331(d)].

We note that your website references an “FDA enforcement discretion policy” regarding FMT. In November 2022, FDA issued a revised guidance titled, “Enforcement Policy Regarding Investigational New Drugs Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridioides difficile Infection Not Responsive to Standard Therapies”. This guidance document indicates that FDA intends to exercise enforcement discretion regarding the IND requirements for the use of FMT in treating Clostridioides difficile (C. difficile) infection not responding to standard therapies, where, among other things, 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 and use of the FMT product does not raise reported safety concerns or potential significant safety concerns.

Based on a review of your website, you offer FMT for treatment of diseases and conditions other than C. difficile infection. As noted in FDA’s November 2022 guidance, 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 other uses is not included in the aforementioned enforcement policy. In addition, although your website recommends that patients “discuss their plans with their doctor,” it offers your products directly to patients, including for self-administration. For example, your website indicates that donors can ship your products directly to patients and provides instructions on methods of self-administration. Therefore, there is no assurance that a licensed health care provider treating each of these patients is directing the screening and testing of the stool donor and stool for the patient, as described in the November 2022 guidance. Your products also raise potential significant safety concerns due to inadequate donor screening. We also note the reported safety concerns described in the “donor results spreadsheet” on your website (e.g., “increased intestinal pain, nausea, sweating, and loss of appetite among other things”). For these reasons, your products would not fall within the enforcement discretion policy referenced above.

The violations cited in this letter are not meant to be an all-inclusive list of violations that may exist in connection with your products. You are responsible for promptly investigating and determining the causes of any violations, correcting them, and preventing their recurrence, and ensuring full compliance with the law.

We advise you to comprehensively review your website and other labeling and marketing materials to ensure that you are lawfully marketing your products in full compliance with the FD&C Act, the PHS Act, and their implementing regulations. Failure to adequately address this matter may result in enforcement action without further notice, including, without limitation, seizure and/or injunction.

This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. If you believe that your products are not in violation of the FD&C Act and the PHS Act, include your reasoning and any supporting information for our consideration in your response to this letter.

Within fifteen working days of receipt of this letter, please notify FDA in writing of the specific steps that you have taken to correct any violations. Your response should include an explanation of each step being taken to prevent the recurrence of violations as well as related documentation. If you cannot complete all corrective actions within fifteen working days, state the reason for the delay and the date by which you will complete the correction.

Your written response should be sent to the following address: U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, Document Control Center, 10903 New Hampshire Avenue, WO71-G112, Silver Spring, MD 20993-0002. Please also email your response to CBERDCMRecommendations@fda.hhs.gov.

Sincerely,
/S/

Melissa J. Mendoza
Director, Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research

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1 FMT is a live biotherapeutic product composed of microorganisms. Microorganisms are not human cells or tissues and do not meet the definition of HCT/P (see 21 CFR 1271.3(d)).