FDA regulation of cell therapy treats most products that contain human cells as biologics needing approval before marketing. A narrow group of minimally processed tissue products is regulated more lightly, and the line between the two is the source of much confusion.
This guide explains how the agency sorts these products and what the categories mean for readers. It forms part of the stem cell research section of this independent educational site.
The agency’s tiered approach to human cells and tissues
The FDA’s guidance on minimal manipulation and homologous use defines the product class. It states that human cells, tissues, and cellular and tissue-based products (HCT/Ps) are articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient.
The guidance adds that, because of the unique nature of these products, FDA proposed and in 2005 implemented a tiered, risk-based approach to their regulation. Products that meet specific criteria or fall within detailed exceptions do not require premarket review and approval, while the rest do.
In plain terms, a cell-based product is not automatically exempt from oversight because it comes from a person. The tier it falls into depends on how it is processed and what it is intended to do.
The two tests that decide the tier
According to the same guidance, one criterion for a product to be regulated solely under section 361 of the Public Health Service Act is that it is minimally manipulated. For cells or nonstructural tissues, the guidance defines this as processing that does not alter the relevant biological characteristics of cells or tissues.
A second criterion is homologous use. The guidance defines it as the repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with a product that performs the same basic function or functions in the recipient as in the donor.
The intent is judged from the manufacturer’s behaviour. The guidance says homologous use only is reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent. It also states that a product intended for use as an unproven treatment for a myriad of diseases or conditions is likely not intended for homologous use only.
A product that does not meet the criteria is handled differently. The guidance says it will be regulated as a drug, device, and/or biological product, and/or under section 351 of the Public Health Service Act, and that premarket review will be required.
What approval requires and what is approved
For stem cell products specifically, the agency’s consumer alert states that stem cell products are regulated by FDA and that, generally, all stem cell products require FDA approval. In that 2020 alert, the FDA said the only stem cell products then approved for use in the United States consisted of blood-forming stem cells derived from umbilical cord blood, approved for patients with disorders that affect the production of blood. On December 18, 2024, the FDA approved Ryoncil, a donor bone marrow-derived mesenchymal stromal cell therapy, for steroid-refractory acute graft-versus-host disease in children; the FDA’s list of approved cellular and gene therapy products is the current reference.
The alert also notes that exosome products are regulated and that there are currently no FDA-approved exosome products. The page is dated July 22, 2020, so readers should check the agency’s current pages for any later changes.
Beyond that narrow stem cell category, the FDA publishes a list of licensed cellular and gene therapy products from its Office of Therapeutic Products. Engineered immune cell treatments such as CAR T cell therapy are regulated on this biologic pathway, which is why their development runs through formal trials.
Unapproved products and the clinical trial route
The FDA’s patient and consumer information page, dated June 3, 2021, says there continues to be broad marketing of unapproved products considered regenerative medicine therapies that are intended for the treatment or cure of a wide range of diseases or medical conditions. It states that these products require FDA licensure or approval to be marketed to consumers, and that before approval they require FDA oversight in a clinical trial.
The page lists examples of unapproved products, whether recovered from your own body or another person’s body, including stem cells, stromal vascular fraction (fat-derived cells), umbilical cord blood, amniotic fluid, Wharton’s jelly, ortho-biologics and exosomes.
It also says the agency has repeatedly notified manufacturers, clinics and health care practitioners of the need for Investigational New Drug applications to legally administer these products and to ensure safety measures are in place before administration.
The agency is specific about conditions. Its patient information page states that regenerative medicine therapies have not been approved to treat any neurological disorder, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, epilepsy, or stroke. It also says they have not been approved for the treatment of any orthopedic condition, such as osteoarthritis, tendonitis, disc disease, or back pain.
The same list covers cardiovascular or pulmonary diseases, such as heart disease, emphysema, or chronic obstructive pulmonary disease. For readers, the practical meaning is simple: a clinic advertising such a use outside a trial is advertising something the agency says is not approved.
The same page warns that being charged for these products or being offered them outside of a clinical trial may indicate deception. Specifically, it says that if you are being charged for these products or offered these products outside of a clinical trial, you are likely being deceived and offered a product illegally.
Registration is not approval
One misleading claim deserves its own mention. The patient information page says FDA is aware that patients are referred to clinicaltrials.gov, or told that a product is registered with FDA, as a way to suggest the products are in compliance. It calls this often false, because inclusion in the database, or a firm registering and listing its product, does not mean the product is legally marketed.
Research ethics standards address related concerns from the research side. The principles for responsible translation in the ISSCR guidelines sit alongside, not in place of, legal requirements.
The patient information page also lists safety concerns for any product illegally marketed as a regenerative medicine therapy, including blindness, tumor formation, neurological events and bacterial infections including life-threatening blood infections. It asks anyone harmed to report to the agency’s adverse event program.
Additional safety concerns on the page include cells moving to another part of the body and turning into an unintended type of tissue or excessively growing in the body, unwanted inflammatory or immune response to the cell or therapy, and cross-contamination with bacteria, viruses or mold related to processing. These items show why oversight focuses on manufacturing and testing as well as on the claims made.
A regulatory category is not medical advice. Decisions about any treatment belong with a licensed physician who knows the reader’s situation.
Frequently asked questions
Do all stem cell products need FDA approval?
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The agency’s consumer alert states that, generally, all stem cell products require FDA approval, with the approved ones limited to cord blood-derived blood-forming cells at the time of that alert. The FDA has since also approved Ryoncil, a donor mesenchymal stromal cell product, for steroid-refractory acute graft-versus-host disease in children.
What does minimal manipulation mean?
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For cells, it means processing that does not alter the relevant biological characteristics of the cells or tissues.
Does a clinicaltrials.gov listing mean a product is legal to market?
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No. The FDA states that inclusion in the database does not mean the product is legally marketed.
What is homologous use?
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It is the repair, reconstruction, replacement or supplementation of cells or tissues with a product that performs the same basic function in the recipient as in the donor.
