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  5. Mother Stem Institute, Corp. - 680118 - 08/20/2024
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WARNING LETTER

Mother Stem Institute, Corp. MARCS-CMS 680118 —

Delivery Method:
VIA UNITED PARCEL SERVICE SIGNATURE REQUIRED
Reference #:
CBER-24-680118
Product:
Biologics
Recipient:
Recipient Name
Alvaro Skupin, M.D.
Recipient Title
Founder
Mother Stem Institute, Corp.

2100 Ponce De Leon #1080
Coral Gables, FL 33134
United States

Issuing Office:
Center for Biologics Evaluation and Research (CBER)

United States

WARNING LETTER

Date: August 20, 2024

Dear Dr. Skupin:

This is to advise you that the United States Food and Drug Administration (FDA) has reviewed your website at www.mothersteminstitute.com in August 2024 as well as your firm’s response to the agency’s records request under section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. § 374(a)(4)] sent on February 16, 2024, which contains information relating to your recovery and processing of adipose tissue, a structural tissue, from donors for autologous use as “stem cells.” You process adipose tissue into stromal vascular fraction (SVF) (hereinafter, “your SVF product”). Per your firm’s response, your firm uses enzymatic digestion (b)(4) to isolate cellular components from adipose tissue. That response also indicated that your SVF product is administered intravenously. Information from your website reflects your product is intended for use in the treatment of a variety of diseases and conditions. For example, your website (last visited August 2024) states the following:

  • Under a title of “Alzheimer’s and Stem Cells”: “Stem cells obtained from the patient’s own fat (autologous) have opened a new door to conquer Alzheimer’s disease because they manage to transform into the type of cells that the patient has lost. Not only does this suppress the death (apoptosis) of neurons in the brain, but it also has a preventative and therapeutic effect against Alzheimer’s disease.” In the same article, it states “A 73-year-old female patient comes to the clinic because two years ago the family reports that she frequently forgets where to leave objects, does not recognize relatives, does not participate in family celebrations, has moderate anxiety, tiredness during the day and is diagnosed with Alzheimer's…In July 2014, she underwent the stem cell procedure. At the end of the four months, the patient expresses feeling better, has more concentration to do household chores and feels more energy.”
  • Under a title of “Intravenous Stem Cell Therapy”: “Stem cells have the ability to identify injured organs and tissues in the body, regenerating the damage found in their wake. The treatment consists of administering intravenously the patient’s own stem cells (autologous).”
  • Under a title of “Who benefits from Stem Cell Treatment”: “People who have common symptoms such as physical exhaustion, stress, insomnia, as well as people with chronic degenerative diseases such as type I and II diabetes, osteoarthritis, Parkinson’s. It also favors people with autoimmune and inflammatory diseases such as Lupus, Rheumatoid Arthritis. An extensive list of diseases can be mentioned…” “The best thing is this treatment is available to everyone in our facilities…”

These claims on your website establish that you intend your SVF product to be used for the treatment of various diseases and conditions, including Alzheimer’s disease, Type I/II Diabetes, Lupus, and Rheumatoid Arthritis. These intended uses indicate that the product is a drug under section 201(g)(1)(B) and (C) of the FD&C Act [21 U.S.C. § 321(g)(1)(B)-(C)] because it is intended for use in the mitigation, treatment, or prevention of disease and because it is intended to affect the structure or function of the body. Additionally, your product is a biological product as defined in section 351(i) of the Public Health Service Act (PHS Act) [42 U.S.C. § 262(i)] because it is applicable to the prevention, treatment, or cure of a disease or condition of human beings.

Further, your SVF product is a human cell, tissue, or cellular or tissue-based product (HCT/P) as defined in 21 CFR 1271.3(d) that is subject to regulation under 21 CFR Part 1271, issued under the authority of section 361 of the PHS Act [42 U.S.C. § 264]. HCT/Ps that do not meet all the criteria in 21 CFR 1271.10(a), and when no exception in 21 CFR 1271.15 applies, are not regulated solely under section 361 of the PHS Act [42 U.S.C. § 264] and the regulations in 21 CFR Part 1271. Such products are regulated as drugs, devices, and/or biological products under the FD&C Act and/or the PHS Act, and are subject to additional regulation, including premarket review. Based on our review of the materials described above, your firm does not qualify for any exception in 21 CFR 1271.15, and your above-referenced product fails to meet the criteria in 21 CFR 1271.10(a).

For example, you do not qualify for the exception in 21 CFR 1271.15(b), which provides that an “establishment that removes HCT/P’s from an individual and implants such HCT/P’s into the same individual during the same surgical procedure” is excepted from FDA regulations in 21 CFR Part 1271. The HCT/P that you remove from patients – adipose tissue – is different from the HCT/P that you later administer to patients – your SVF product. In its original form, adipose tissue is a structural tissue composed of cells surrounded by a reticular fiber network and interspersed small blood vessels.1 According to your response to FDA’s record request, you break down that adipose tissue using enzymatic digestion and isolate cellular components. What remains of the adipose tissue following your enzymatic digestion, filtration, and centrifugation is not considered tissue. Rather, the organized structure of the adipose tissue has been destroyed and, biologically, what remains would be a heterogeneous collection of cells.2 Therefore, your SVF product is not “such HCT/P” within the meaning of 21 CFR 1271.15(b), and the same surgical procedure exception does not apply.

Furthermore, your SVF product fails to meet the minimal manipulation criterion set forth in 21 CFR 1271.10(a)(1) and defined for structural tissue in 21 CFR 1271.3(f)(1). Adipose tissue is typically defined as a connective tissue composed of clusters of cells (adipocytes) surrounded by a reticular fiber network and interspersed small blood vessels, divided into lobes and lobules by connective tissue septa; therefore, the FDA considers adipose tissue to be a structural tissue for the purpose of applying the regulatory framework.3 Additionally, adipose tissue contains other cells, including preadipocytes, fibroblasts, vascular endothelial cells, and macrophages.4 Adipose tissue provides cushioning and support for other tissues, including the skin and internal organs, stores energy in the form of lipids, and insulates the body, among other functions. Structural tissues, like adipose tissue, may contain both extracellular matrix and cellular components, and any alteration of these components that relates to the structural tissue’s utility for reconstruction, repair, or replacement generally would be considered more than minimal manipulation. To assess whether a processing step alters the original relevant characteristics of a structural tissue relating to its utility for reconstruction, repair, or replacement, the effects of the processing on the properties that contribute to the specific tissue’s function in the donor are considered. Thus, whether processing of adipose tissue would meet the regulatory definition of minimal manipulation takes into consideration whether the processing alters the original relevant characteristics of the adipose tissue related to its utility to provide cushioning and support to the body.

Adipose tissue is processed by Mother Stem Institute using enzymatic digestion to isolate cellular components of adipose tissue, i.e., SVF. This processing to isolate non-adipocyte or non-structural components from adipose tissue (with or without subsequent cell culture or expansion) is more than minimal manipulation because removing the adipocytes and structural components alters the original relevant characteristics relating to the tissue’s utility to provide cushioning and support. Unlike adipose tissue, your SVF product does not provide cushioning and support.5

To lawfully market a drug that is also a biological product, a valid biologics license 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. 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 SVF product is not the subject of an approved biologics license application (BLA) nor is there an IND in effect.

Furthermore, your SVF product is a misbranded drug under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)]. A drug is misbranded under section 502(f)(1) if the drug fails to bear adequate directions for its intended use(s). “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended [21 CFR 201.5]. Prescription drugs, as defined in section 503(b)(1)(A) of the FD&C Act [21 U.S.C. § 353(b)(1)(A)], can only be used safely at the direction, and under the supervision, of a licensed practitioner.

Your SVF product is intended for treatment of one or more diseases that are not amenable to self-diagnosis or treatment without the supervision of a licensed practitioner. Therefore, it is impossible to write adequate directions for a layperson to use your SVF product safely for its intended purposes. Accordingly, your SVF product fails to bear adequate directions for its intended uses and, therefore, is misbranded under section 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)]. Misbranding your SVF product while it is held for sale after shipment of the drug or one or more of its components in interstate commerce is prohibited under section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].

The violations cited in this letter are not meant to be an all-inclusive list of violations that may exist in connection with your product. 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

______________________

1 Chapter 6. Adipose Tissue. In: Mescher AL. eds. Junqueira's Basic Histology: Text & Atlas, 13e. New York: McGraw-Hill; 2013. http://accessmedicine.mhmedical.com/content.aspx?bookid=574&Sectionid=42524592.

2 Id.

3 Id.

4 Brown SA, Levi, B, Lequeux, C, et al. Basic Science Review on Adipose Tissue for Clinicians. Plast. Reconstr. Surg. 126:1936, 2010

5 Because your SVF product fails to meet at least one criterion in 21 CFR 1271.10(a), this letter does not address other criteria in 21 CFR 1271.10(a).

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