The Two Federal Lists That Decide What a Pharmacy May Compound

Answer first: two short lists, in one place

Part 216 of title 21 of the Code of Federal Regulations is titled Human Drug Compounding. At the issue date read here it contains exactly two operative sections, and they do opposite jobs.

One is a permission list. It names bulk drug substances that can be used in compounding under a specific clause of section 503A of the Federal Food, Drug, and Cosmetic Act.

The other is a prohibition list. It names drug products withdrawn or removed from the market for reasons of safety or effectiveness, and says those products may not be compounded under the exemptions provided by section 503A(a) or section 503B(a).

Both are short enough to read in full, which is unusual for a federal regulation and is the reason this is worth doing yourself rather than trusting a summary.

The prohibition list, and what it is for

The section opens with its own explanation. The listed products were withdrawn or removed from the market because such drug products, or components of them, have been found to be unsafe or not effective.

Then comes the operative sentence. The listed drug products may not be compounded under the exemptions provided by section 503A(a) or section 503B(a) of the Act.

That covers both kinds of compounder in one line. A pharmacy compounding for an identified patient and an outsourcing facility making batches are both inside the same prohibition.

The purpose is easy to state. Section 503A and section 503B are exemptions from requirements that ordinarily apply to drugs, and this list stops those exemptions being used to bring back something the market already rejected.

How the entries are actually written

The list is not a list of molecules with a blanket ban attached. Read the entries and you find three different shapes.

Most are total. The entry for cisapride reads: all drug products containing cisapride. Same for rofecoxib, terfenadine, phenacetin and many others.

Some are limited by route or dosage form. Chloramphenicol is listed as all oral drug products containing chloramphenicol. Butamben is listed for all parenteral products. Trichloroethane is listed for all aerosol products intended for inhalation.

Some carve out an exception in the entry itself. Bromfenac sodium is listed except for ophthalmic solutions. Gatifloxacin and suprofen carry the same ophthalmic exception. Nitrofurazone is listed except for topical products formulated for dermatologic application.

And a few turn on an amount. Reserpine is listed for oral dosage forms containing more than one milligram. Diethylstilbestrol is listed for oral and parenteral products containing twenty-five milligrams or more per unit dose.

One entry is written by indication rather than by product. Bromocriptine mesylate is listed for the prevention of physiological lactation, not generally.

No GLP-1 medication appears on it

This is the question most readers actually arrive with, so here is the answer with its scope attached.

The prohibition section was read end to end at the issue date cited below. Its entries run alphabetically, opening with adenosine phosphate and closing with zomepirac sodium.

Across that whole span, no entry names semaglutide, tirzepatide, liraglutide, exenatide or dulaglutide. No entry names a GLP-1 receptor agonist by class either.

What that does and does not settle is worth being exact about. It means the specific prohibition in this section does not reach those substances. It says nothing about whether any other rule does, and it is not a statement that a compounded version is approved, endorsed or checked.

It also decays. A list published by rulemaking changes by rulemaking, and the only current version is the one on the page cited below on the day you read it.

The permission list is very short

The other section handles the opposite case, and its brevity is the point.

It names bulk drug substances that can be used in compounding under section 503A(b)(1)(A)(i)(III) of the Act. The regulation numbers them (1) through (6).

The first is Brilliant Blue G, also known as Coomassie Brilliant Blue G-250. Then cantharidin, for topical use only. Then diphenylcyclopropenone, for topical use only.

Then N-acetyl-D-glucosamine, for topical use only. Then squaric acid dibutyl ester, for topical use only. And last, thymol iodide, for topical use only.

Five of the six carry a route restriction written into the entry. That restriction is part of the listing, not a footnote to it.

The regulation also names what it turned down

This is the unusual part, and it is useful to anyone reading a marketing claim about an ingredient.

The same section states that after balancing its criteria, FDA determined that four named substances will not be included on the permission list. The regulation numbers them (1) through (4): oxitriptan, piracetam, silver protein mild and tranilast.

So the regulation records both a yes and a no, in the same place, with the criteria printed between them.

Those criteria are four. The physical and chemical characterization of the substance. Any safety issues raised by its use in compounded drug products. The available evidence of effectiveness or lack of effectiveness, if any such evidence exists. And historical use in compounded drug products, including the conditions it has been used to treat and any references in peer-reviewed medical literature.

Being on a list is not an approval, and the regulation says so

The permission section closes with a paragraph that reads like it was written in response to marketing, because it plainly was.

Based on evidence currently available, the regulation states, there are inadequate data to demonstrate the safety or efficacy of any drug product compounded using any of the listed substances. The same sentence adds that the data are also inadequate to establish general recognition of the safety or effectiveness of any such product.

Then the consequence. Take a compounded drug made with a bulk drug substance on this list. Any person who represents it as FDA approved, or otherwise endorsed by FDA generally or for a particular indication, will cause the drug to be misbranded.

That is as direct as a regulation gets. Appearing on a federal list is not approval, and saying otherwise is itself a violation.

Carry the same reading over to the prohibition list. Absence from it means the specific prohibition does not apply. It is not a clearance, and nobody has evaluated anything by leaving it out.

How to use this when you are reading a seller

Start by noticing which list a claim is reaching for. A claim about an ingredient being listed points at the permission section; a claim about a product being allowed usually points at the absence of a prohibition.

Check the claim against the actual text rather than a paraphrase, because both lists are short and the entries carry conditions. A route restriction, a dose threshold or an ophthalmic exception changes what a listing means.

Treat the word approved as a red flag next to either list. The regulation says representing a compounded drug made from a listed substance as FDA approved or endorsed causes misbranding.

And keep the two questions separate, the way the rules do. Whether a substance may lawfully be compounded with is one question. Whether any particular batch is what its label says is a different one, and no list answers it.