Two pathways, one starting question
Classification depends on the specific material, processing, and intended use; counsel should assess the applicable framework for a given product. Every human cell, tissue, and cellular or tissue-based product, shortened to HCT/P, is evaluated against two possible pathways: regulation solely under section 361 of the Public Health Service Act, or review as a biologic drug under section 351.
A product regulated solely under section 361 is governed mainly through establishment registration, donor eligibility screening, and the processing and recordkeeping requirements in 21 CFR Part 1271. Exosome products are generally regulated as section-351 biologic drugs. An IND concerns investigational studies and is not marketing authorization; regulatory counsel should assess the applicable requirements for any specific product before it is marketed.
The classification is not a label a supplier assigns once and keeps forever. It is a determination tied to a product's processing and its intended use, and both the supplier and the parties handling the product afterward are expected to be able to explain why a given product sits where it sits.
The four-part test for staying under section 361 (361 vs 351 hct/p)
21 CFR 1271.10(a) sets out four criteria. A product must meet all four to qualify for regulation solely under section 361:
- The tissue is minimally manipulated.
- It is intended for homologous use only, meaning it performs the same basic function in the recipient that it performed in the donor.
- It is not combined with another article, with narrow exceptions for water, crystalloids, and certain sterilizing or preserving agents.
- It either has no systemic effect and does not rely on the metabolic activity of living cells for its primary function, or it is for autologous use, reproductive use, or allogeneic use in a first- or second-degree relative.
What pushes a product toward section 351
If a product's labeling or marketing describes a use beyond the tissue's original basic function, the homologous use criterion is where a section 361 determination is most likely to fail, because intended use is established by labeling, marketing claims, and the circumstances of distribution, not by the tissue's origin alone. Two products derived from similar donor tissue can land on opposite sides of this line if one is labeled and promoted for a use that is not homologous.
FDA states there are no FDA-approved exosome products. They are generally regulated as biologic drugs under section 351. Purchase and clinical-use decisions for these products belong to the physician, in consultation with their own regulatory counsel.
Classification is a determination, not a marketing choice
Calling a product a '361 tissue allograft' on a label or a website does not make it one. FDA's recent warning letters to distributors of private-label perinatal products show the agency reading website content and social posts as evidence of a product's actual intended use, separate from what the processing description says.
That means a distributor's marketing and a clinic's own marketing can independently affect how a product is viewed, even when the processing and donor documentation behind it would otherwise support a section 361 posture.
What to request before you buy or sell
Clinics evaluating a perinatal biologics supplier, and distributors building out a catalog, both benefit from asking the same basic questions before the first order:
- What is the written basis for a section 361 determination, if one has been made, and who made it?
- Can the supplier produce a processing description, donor eligibility summary, and certificate of analysis for the specific lot?
- Does the product's labeling and marketing describe a homologous use, and does downstream marketing match that description?
- If the product is an exosome or extracellular vesicle preparation, has counsel reviewed it against the biologic drug framework rather than assuming a section 361 posture?
A starting map, not a legal opinion
This overview explains the structure of the 361 versus 351 decision. It is not legal advice, and it does not substitute for review by FDA regulatory counsel familiar with a specific product, its processing records, and its intended use. Classification questions are fact-specific, and getting them wrong carries real exposure for distributors and for the clinics that buy from them.
These products are not FDA approved or licensed for any disease or condition. Information is for licensed healthcare professionals and is not medical or legal advice.
Frequently asked questions
Is a Wharton's jelly allograft automatically regulated under section 361?+
No. It can qualify for section 361 if it meets all four criteria in 21 CFR 1271.10(a), including minimal manipulation and homologous use, but the determination depends on the specific product and its intended use, not on the tissue type alone.
Are exosome products regulated under section 361?+
Generally not. FDA states there are no FDA-approved exosome products, and they are generally regulated as biologic drugs under section 351 rather than qualifying for the section 361 exemption. Purchase and clinical-use decisions for exosome products belong to the physician and their own regulatory counsel.
Who makes the section 361 versus 351 determination?+
FDA makes the ultimate determination, but distributors, clinics, and their regulatory counsel are expected to assess a product's processing and intended use against the 1271.10 criteria before marketing or purchasing it.
Can marketing claims change a product's classification?+
Yes. Claims that describe a use beyond homologous use, or that imply a systemic effect, can shift how FDA views a product's intended use, which can move it from the section 361 framework into the section 351 drug pathway regardless of how the tissue was processed.