Physician stem cell therapies legally ambiguous, while regenerative clinics prosper

Recent press calls into question widespread “regenerative” and anti-aging medicine, and physician practices that use stem cell therapies. For example:

What accounts for the success of anti-aging, stem-cell based, and regenerative medicine, notwithstanding charges that stem cell therapies go unregulated?

FDA Regulation of Stem Cell Therapies

First of all, FDA does regulate stem cell therapies. FDA does not regulate the practice of medicine, which is controlled by state law.

Physicians have often relied on the argument that they are merely “practicing medicine” and thus outside FDA purview. But FDA disagrees in the case of stem cell therapies.

FDA regulates stem cells in the U.S. to ensure that they are safe and effective for their intended use.

FDA’s advice for consumers is essentially that most physician use of stem therapies is unapproved by FDA:

FDA cautions consumers to make sure that any stem cell treatment they are considering has been approved by FDA or is being studied under a clinical investigation that has been submitted to and allowed to proceed by FDA.

FDA has approved only one stem cell product, Hemacord, a cord blood-derived product manufactured by the New York Blood Center and used for specified indications in patients with disorders affecting the body’s blood-forming system….

If you are considering stem cell treatment in the U.S., ask your physician if the necessary FDA approval has been obtained or if you will be part of an FDA-regulated clinical study. This also applies if the stem cells are your own. Even if the cells are yours, there are safety risks, including risks introduced when the cells are manipulated after removal.

Because stem cell products are considered biologic drugs, FDA regulates stems cells through its Center for Biologics Evaluation and Research (CBER), not its drug approval center.

Federal Stem Cell Rules: HCT/P Regulations

The relevant law is Section 361 of the Public Health Service Act (providing authority for FDA to establish regulations for all HCT/Ps to prevent the introduction, transmission, and spread of communicable diseases) and a series of rules known as the HCT/P regulations. There are also FDA guidance documents such as: Guidance for Industry: Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) – Small Entity Compliance Guide.

Here are key points:

  • HCT/P stands for: human cells, tissues, and cellular and tissue-based products.
  • The regulations create a unified registration and listing system for establishments that manufacture human cells, tissues, and tissue-based products.
  • Anyone who “manufactures” HCT/P must comply with the HCT/P regulations.
  • Compliance includes registration with FDA’s CBER.
  • Manufacture means, but is not limited to, any or all steps in the recovery, processing, storage, labeling, packaging, or distribution of any human cell or tissue, and the screening or testing of the cell or tissue donor.

Critically, the following conditions must be met:

  1. HCT/P’s must be minimally manipulated.
  2. HCT/P’s must be intended for homologous use only, as reflected in the labeling, advertising, or other indications of the manufacturer’s objective intent.
  3. The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, with certain stated exceptions.
  4. Either: (i) The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function; or (ii) The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and: (a ) Is for autologous use; (b ) Is for allogeneic use in a first-degree or second-degree blood relative; or (c ) Is for reproductive use.

Two key definitions:

  • Homologous use means the repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor….
  • Minimal manipulation means:
    • For structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement; and
    • For cells or nonstructural tissues, processing that does not alter the relevant biological characteristics of cells or tissues.

Can physicians practice regenerative medicine outside these rules? Let’s look at the Regenerative case.

FDA Fights the “Practice of Medicine” Argument—The Regenerative Case

In U.S. v. Regenerative Sciences, LLC, FDA defended its 2008 warning letter which cited Regenerative Sciences for violating FDA’s stem cell regulations. Both the trial court and the appellate court agreed with FDA.

The trial court found that the stem cell products were more than “minimally manipulated,” because culturing the stem cells affected their characteristics. This meant that the stem cell therapy fell outside the protection of the HCT/P regulations.

The DC District Court of Appeals found that Regenerative’s procedure resulted in a product that was a “drug,” not an HCT/P under 21 CFR 1271. This meant that the stem cell product was subject to FDA regulation as a drug. According to the Court, FDA was not regulating the procedure, but the product – i.e., the mixture containing stem cells and the antibiotic, doxycycline. The Court cited the broad definition of “drug” in the FDCA as any article “intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” or “intended to affect the structure of any function of the body.” The therapeutic claims made by the company were more than sufficient to show an intended use to treat or mitigate disease.

Because FDA could regulate the mixture as a drug (as it was intended to treat orthopedic diseases), and therefore, that Regenerative was subject to current Good Manufacturing Practices (cGMPs) applicable to all drugs.

As part of its rationale, Court also cited the definition of “biological product” in the PHSA as any “virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative … or analogous product … applicable to the prevention, treatment, or cure of a disease or condition of human beings.” Again, since the stem cell product was intended to treat disease, it fell within the definition of a biological drug, requiring FDA approval.

In short, the Regenerative company’s product did not fall within the HCT/P regulations, did not constitute the “practice of medicine” under state law, and, was subject to FDA biologic drug approval. There was no end run around the FDA.

FDA Warning Letters

FDA issued a warning letter in the past to a medical spa that injected stem cells for “natural breast augmentation.”

In a 2014 warning letter to Cell Vitals, FDA went after “ReLuma Advanced Stem Cell Facial Moisturizer,” “ReLuma Skin Illuminating Stem Cell Anti-Aging Cleanser,” and “ReLuma Stem Cell Eye Cream.”

In addition to violations involving stem cell claims, FDA has apparently also issued warning letters for violations of stem cell regulations that have surfaced in inspections. (See FDA Inspection Trends for Cellular Therapies).

In short, FDA is active in enforcing both the HCT/P regulations, and, its mandate to regulate biologic drugs.

Stem Cell Legislation

One has to bear in mind not only federal regulation of stem cell products, but also any relevant state law or state medical board rules. For example, the state medical board may not have any explicit regulation, but may regard stem cell therapies as experimental, and subject physicians who employ such therapies to medical board discipline.

In California, Prop 71 created the Institute for Regenerative Medicine, to make grants and loans for stem cell research, support the development of stem cell-based therapies to cure diseases, and to establish appropriate regulatory standards and oversight bodies for research and facilities development. Or course, stem-cell based therapies must comply with all applicable federal and state laws.

Texas has medical board rules governing therapeutic use of stem cell therapies.

Not HCT/P’s

The stem cell regulations provide examples of what are not HCT/P’s:

  • Vascularized organs
  • Minimally manipulated bone marrow
  • Tissues intended for educational or non-clinical research use (not intended for transplantation)
  • Xenografts
  • Blood products
  • Secreted or extracted products; e.g., human milk, collagen, cell factors
  • Ancillary products used in manufacture
  • In vitro diagnostic products
  • Blood vessels recovered with an organ

What Physicians Practicing Regenerative and Anti-Aging Medicine Need to Know

Increasing press attention to physician use of stem cell therapies may be a harbinger of increased regulation to come.

The articles cited above discuss one case involving physician use of stem cell therapies where the patient died, the physician lost his license to practice, and the same doctor opened a stem cell therapy center offshore:

More than 170 clinics across the country are selling experimental stem cell procedures for dozens of diseases and conditions — a mushrooming industry that has flourished despite little evidence of its safety or effectiveness….

The rise of the U.S. stem cell industry illustrates how quickly fringe medicine can outpace government oversight…

State actions against stem cell doctors are rare. That’s led industry critics to conclude that regulation must come from the FDA, which regulates medical products on a national level….

One national chain markets itself online with accounts of celebrity athletes who have been treated with its stem cell procedures. Prospective patients are then directed to a call center, where sales representatives try to match them with stem cell doctors over the phone.

As we’ve pointed out, the bottom line for physicians practicing regenerative and anti-aging medicine is that:

  • FDA maintains that a stem cell product cannot get to market unless it is either approved by FDA or studied under a clinical investigation that has been submitted and allowed to proceed by FDA.
  • FDA has approved relatively few stem cell products.
  • Stem cell products must comply with the HCT/P regulations, which among other things, require registration and listing.
  • Culturing stem cells constitutes more than “minimal manipulation” (i.e., FDA approval as a biologic drug is required).

To seek legal counsel regarding stem cell therapy or other healthcare products and services, contact our healthcare law and FDA legal team..

Michael H Cohen Healthcare & FDA Lawyers

Contact our healthcare law and FDA attorneys for legal advice relevant to your healthcare venture.

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