351 or 361: which rule covers the product in my clinic?

Written by Oscar Tellez, founder of Regen Med Academy. Oscar is not a clinician. This post is education for licensed providers and is not medical advice. Last updated November 4, 2026.

It depends on four tests in one federal rule, 21 CFR 1271.10(a). A human cell or tissue product, called an HCT/P, is covered by section 361 alone only if it meets all four. If it misses even one, it is regulated as a drug, a device or a biologic, and that is the section 351 side. This post takes the 351 vs 361 question one test at a time, in the rule’s own words.

What are section 351 and section 361?

When a doctor calls me, the first thing they ask is, are stem cells legal or illegal? This is how I answer: “Stem cells are a category, not a product.” Then I ask the next question: “What type of stem cell are you talking about? Let’s talk specifics.”

The rule does the same thing. It does not ask whether a whole category is allowed. It asks four questions about one product and about how that product is used.

Start with the two numbers. Both are sections of a federal law called the Public Health Service Act, or PHS Act. Section 361 lets the government make rules “to prevent the introduction, transmission, or spread of communicable diseases.” For cell and tissue products, think of rules meant to keep disease from spreading.

Section 351 is about a license. It says no person may ship a biological product across state lines unless “a biologics license” is “in effect for the biological product.”

So here is the short version. A 361 product is regulated only to control the spread of disease. A 351 product also needs FDA’s review and a license before it is sold.

These products go by the short name HCT/P. The rule defines them as “articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient.” In plain words, an HCT/P is human cells or tissue meant to be put into a person.

What are the four criteria for a 361 HCT/P?

The four tests are in 21 CFR 1271.10(a). The rule opens this way: “An HCT/P is regulated solely under section 361 of the PHS Act and the regulations in this part if it meets all of the following criteria:”

1. “The HCT/P is minimally manipulated.” In plain words, the processing did not change what the tissue or the cells are.
2. “The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent.” In plain words, it is meant to do the same basic job in the patient that it did in the donor.
3. It is not combined with another article, “except for water, crystalloids, or a sterilizing, preserving, or storage agent.” That means nothing else is mixed in.
4. It “does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function.” If it does either one, it can still pass in three cases. Those are autologous use, use in a close blood relative, and reproductive use.

Look at the word all in that opening sentence. A product does not pass with three out of four. It has to meet every one, and it has to meet them for the way it is really made and used.

What does minimally manipulated mean?

The rule defines the term in 21 CFR 1271.3(f). It has two halves, and the kind of tissue decides which half you use.

The first half is for structural tissue. It says minimal manipulation is “processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement.” That means the processing did not change the features that make the tissue useful for rebuilding or repair.

The second half is for cells and for tissue that is not structural. It says “processing that does not alter the relevant biological characteristics of cells or tissues.” So the cells are still what they were before.

So what counts as structural tissue? FDA’s July 2020 guidance says HCT/Ps that “physically support or serve as a barrier or conduit, or connect, cover, or cushion” are generally considered structural. Its examples include bone, skin, fat, and tendon or ligament.

Ask what the tissue was built to do in the body, and then ask whether the processing changed that. The test looks at what was done to the tissue, however gentle the process sounds in a brochure.

What does homologous use mean?

The rule defines this term in 21 CFR 1271.3(c). It says 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.”

That is a long sentence, and the key words are near the end: the same basic function. In plain words, the product has to do the same basic job in the patient that it did in the body it came from.

So put two questions to any product. What does this tissue do in the body it came from? And is that the job it is being sold to do?

If the two answers do not match, the use does not fit the rule. We show how FDA applies it to fat tissue further down.

Why does my advertising matter to the rule?

Go back to the second test and read how it ends. The use has to be homologous “as reflected by the labeling, advertising, or other indications of the manufacturer’s objective intent.” So the test covers what is in the vial, and it also covers what the company says the vial is for.

FDA’s guidance says the agency determines the intended use from those sources first, and then it applies the definition. A website can be read that way, and so can a brochure or a sales deck.

Here is what I see when that goes wrong. “Every time I see someone get a warning letter, the first thing I do is I review it. In most of the letters I read, the company’s own marketing language is part of the evidence.”

Does this reach a clinic, or only the company that made the product? Read how the rule defines the word manufacture. It covers “any or all steps in the recovery, processing, storage, labeling, packaging, or distribution of any human cell or tissue.” It also covers screening and testing the donor, and it says the list is not complete.

That list is wider than the word suggests. If your clinic does any of those steps, ask your attorney whether your own web pages and ads count too.

What do the third and fourth criteria add?

The third test is about what gets mixed in. The short list of allowed agents is water, crystalloids, and agents that sterilize, preserve or store. Even those must “not raise new clinical safety concerns with respect to the HCT/P.” So ask the vendor what is added to the product, and get the list in writing.

The fourth test has two doors. The first door is for a product that “does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function.” In everyday terms, a systemic effect reaches the body as a whole and not only the spot where the product is placed.

The second door is for a product that does have that kind of effect, or that does depend on living cells. It passes in three cases only: autologous use, use in a first-degree or second-degree blood relative, and reproductive use. The rule defines autologous use as putting cells or tissue “back into the individual from whom the cells or tissue were recovered.”

Here’s the problem with stopping at that word. “It comes from the patient’s own body” is one part of the fourth test. It says nothing about the first test or the second, and the rule requires all four.

What is a 351 biologic, and how does a product become one?

A product lands on the 351 side by missing one of the four tests, unless one of the listed provisions in section 1271.15 applies. The rule that says so is 21 CFR 1271.20. It says the HCT/P will be regulated “as a drug, device, and/or biological product under the act and/or section 351 of the PHS Act.”

What changes at that point? FDA’s guidance finishes the thought in five words: “premarket review will be required.” So FDA has to review the product before it is sold.

And before that review is done? FDA’s patient page on these products says, “Before approval, these products require FDA oversight in a clinical trial.” The same page names the kinds of products FDA means. Its list includes stem cells, fat-derived cells, cord blood, amniotic fluid, Wharton’s jelly and exosomes.

The filing that lets a trial like that begin is called an IND, and it gets its own post later in this series. For exosomes, see our post on using exosome products in a clinic.

What is the same surgical procedure provision, and what is it not?

There is one more provision you will hear about, and it is not one of the four tests. It sits in a separate section, 21 CFR 1271.15(b).

It reads: “You are not required to comply with the requirements of this part if you are 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.”

Three phrases carry the weight in that sentence. They are the same individual, such HCT/P’s, and the same surgical procedure. All three have to be true at once.

FDA wrote a guidance on this provision in November 2017. It says that generally the only processing steps that let tissue remain what it calls “such HCT/P” are “rinsing, cleansing, sizing, and shaping.”

So what is this provision not? It is not a fifth way to pass the four tests, and it is not a general pass for anything done in one visit. It also says nothing about what a clinic may claim.

Whether one procedure fits inside it is a legal question about the facts of that procedure. Take it to your own counsel, and bring the guidance with you.

How does FDA’s July 2020 guidance read the criteria for fat tissue?

FDA wrote a guidance document on how it reads the first two tests. FDA says its guidance documents “do not establish legally enforceable responsibilities.” Read the guidance as FDA’s current thinking, and read the rule as the law.

Fat is a good tissue to test this on, and adipose is simply the medical word for it. On the first test, the guidance says “FDA considers adipose tissue to be a structural tissue.”

It then gives an example. A company processes fat to pull out its cells, and the mix that comes out is often called stromal vascular fraction, or SVF. The guidance says that product “generally is considered more than minimally manipulated.”

Look at how the example describes the processing. It covers fat broken down with enzymes and fat broken down by mechanical force, and it names both. So a process that is mechanical and uses no enzyme does not settle the question by itself.

On the second test, the guidance says the basic functions of fat include cushioning and support, storing energy, and insulating the body. Then it gives an example: a product from fat that is used for musculoskeletal conditions such as arthritis or tendonitis.

FDA’s answer is one sentence: “This is generally not considered a homologous use because regenerating or promoting the regeneration of cartilage or tendon is not a basic function of adipose tissue.”

Generally is FDA’s word. It means the guidance describes a usual view and does not rule on your case. Two things still apply to any fat procedure: the second test, and the cleared indication of the device used to collect the tissue. RMA teaches adipose collection, and RMA does not teach SVF.

What should I ask a vendor, and where is the answer in writing?

Let’s say a rep brings a donor tissue product to your office and tells you it is a 361 product. What do you ask? You ask which rule covers the product, and then you ask where that is in writing.

• In your company’s view, is this a 361 HCT/P or a 351 product?
• How is it processed, step by step?
• What use is it intended for, and does your website say the same thing you are telling me?
• What is added to it?
• Does it contain living cells, and does it depend on them for its main function?
• Can I see the certificate of analysis for this lot?
• Has your company asked FDA how the four tests apply, and can I see the answer?

The last question has a real basis. FDA’s guidance says a sponsor can ask the agency’s Tissue Reference Group for “an Agency recommendation” on how the four tests apply to its product for a given use. A sponsor can also file a Request for Designation to get “a formal Agency decision.”

Even then, read the date on the answer. FDA’s Tissue Reference Group page says its recommendations “are based on the information known at the time and are subject to change.”

Be careful with one answer. If the rep says the company is registered with FDA, that does not answer your question. FDA says “the fact that a firm has registered with FDA and listed its product does not mean the product is legally marketed.”

Your job in that meeting is to collect answers on paper, so your counsel can read them with you. The habit of bringing a written checklist to a vendor meeting comes from Carla Mazzeo, PhD, our science faculty, who wrote one for exosome vendors.

Where does Regen Med Academy fit in this?

RMA is an education company. We sell education and nothing else, which means we do not sell a device or a biologic.

We also cannot tell you which rule covers a product you are being offered. That answer comes from the rule, from FDA, and from your own counsel. What we can do is teach you the terms, so you know what to ask.

Our free FDA legal foundations mini course is the place to start. It takes about 45 minutes, it is self-paced, and it has five lessons.

Frequently asked questions

Is a 361 product FDA approved?

No. Meeting the four tests is not an FDA approval, and nothing in the rule says it is. The 361 rules are about controlling the spread of disease, and they are not a review of what a product is claimed to do. So the word approved does not belong on a 361 product, on its label or on your website.

Do the FDA HCT/P regulations cover stem cell therapy?

They apply one product at a time, which is why the category question never gets a clean answer. FDA’s patient page lists stem cells among the products that “require FDA oversight in a clinical trial” before approval. So ask what the product is, how it is processed and what it is used for, and then run the four tests.

Where does PRP fit in the 351 and 361 framework?

PRP is not sorted by the four tests in this post. FDA’s guidance says PRP “is not an HCT/P under 21 CFR Part 1271 because it is a blood product,” so FDA does not apply the four tests to it. That does not put PRP outside FDA’s rules. We cover its exact status in our post that asks, is PRP FDA approved?

Does using the patient’s own tissue settle the question?

No. Autologous use is one part of the fourth test. The product still has to pass the first test, the second test and the third. The rule says an HCT/P must meet “all of the following criteria,” and that includes tissue that comes from the patient’s own body.

Does a state stem cell law change which rule applies?

No. State law does not override federal law, so the four tests apply in every state. State law in this field changes, sometimes more than once a year. Our reading of each state, with its sources and the date we checked, is on the rules by state page, and it is a starting point, not legal advice.

Is bone marrow an HCT/P under these rules?

The rule has a line on it. It lists “Minimally manipulated bone marrow for homologous use and not combined with another article” among the articles that are not considered HCT/Ps. Read every condition in that line before you lean on it. RMA does not teach bone marrow procedures.

Key takeaways

• Sections 351 and 361 are parts of the Public Health Service Act. A 361 product is regulated to control the spread of disease, and a 351 product also needs FDA’s review and a license.
• An HCT/P falls under section 361 alone only if it meets all four tests in 21 CFR 1271.10(a).
• The first three tests cover how the product is processed, what it is used for, and what is mixed in. The fourth asks whether it acts on the whole body or depends on living cells.
• Intended use is read from labeling and ads, so a company’s own marketing can decide the second test.
• A product that misses one test is regulated as a drug, a device or a biologic, and FDA review comes before it is sold.
• The same surgical procedure provision is a separate rule, and it is not a general pass.
• Ask every vendor which rule covers the product, and ask to see that in writing.

RMA disclosure

Regenerative Medicine Academy (RMA) is an education company. We train licensed providers in some of the techniques this post covers. This post is education only. It is not medical, legal, business, tax or financial advice.

It is your responsibility to confirm the modality is legal in your state for your license. Do that before you book.

Your next step

Pick one product in your practice, or one you have been offered, and write down an answer for each of the four tests. Where you cannot answer, send the question to the vendor and ask for a reply in writing. Then get the free FDA course, and if you want to talk about training, request a date now.