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FDA Stem Cell Guide

361 vs 351: How the FDA Classifies Stem Cell Products

Whether a stem cell product needs FDA pre-market approval depends on how it is classified. That classification comes down to two sections of the Public Health Service Act.

Section 361 products

A human cell or tissue product regulated solely under Section 361 of the Public Health Service Act does not require pre-market approval. Instead, the FDA regulates it primarily to prevent the transmission of communicable diseases. To qualify, an HCT/P must meet all four of the following criteria (21 CFR 1271.10):

  1. Minimally manipulated — the processing does not alter the original relevant characteristics of the tissue.
  2. Homologous use — used to perform the same basic function in the recipient as it did in the donor.
  3. Not combined with another article, except for water, crystalloids, or a sterilizing/preserving/storage agent (with limited exceptions).
  4. Either has no systemic effect and is not dependent on the metabolic activity of living cells for its primary function, or, if it does, is for autologous use, allogeneic use in a first- or second-degree blood relative, or reproductive use.

Typical examples: certain bone, skin, and cornea allografts used for their original structural or barrier function.

Section 351 products

If a product fails any one of the four criteria above, it is regulated as a biological drug under Section 351. That means it requires:

  • An Investigational New Drug (IND) application to be studied in humans.
  • An approved Biologics License Application (BLA) before it can be marketed.
  • Ongoing compliance with current Good Manufacturing Practice (cGMP) requirements.

Most stem cell products fall into this category because their intended use is not "homologous" — for example, injecting expanded adipose-derived stem cells into a knee joint to treat arthritis is not the same function that fat tissue performs in the body.

Why the distinction is often abused

Some clinics market products as if they were 361-regulated (and therefore did not need FDA approval) when the FDA considers them 351 products. The agency has issued warning letters and pursued injunctions against providers who marketed cultured or expanded stem cell products, or products used for non-homologous purposes, without an approved BLA or active IND.

For patients, the practical takeaway is simple: a clinic claiming the FDA "doesn't regulate" its stem cell product is often misstating the rule. The FDA regulates the product; the question is which pathway applies — and for most stem cell offerings, that pathway is 351.