Research
How the FDA bulk substances lists work
A compounding pharmacy cannot use just any powder. Federal law limits it to substances that clear one of three gates, and the lists that decide which peptides qualify are still being built, one nomination at a time.
The question the lists answer
A compounded medication starts as raw material, and the legal term for that material is a bulk drug substance. Before anything else about a compounded peptide matters, one question has to be settled: may a pharmacy lawfully use this powder at all.
Two sections of federal law answer it, and they answer it differently. Section 503A covers a state-licensed pharmacy or a physician. Section 503B covers an outsourcing facility. Each has its own gate and its own list.
Neither list is a rating. A substance on one has not been shown to work, and a substance off one has not been shown to be harmful. The lists describe permission, not merit.
The 503A gate has three doors
FDA states the rule plainly. A pharmacy compounding under section 503A may use a bulk drug substance only if it complies with an applicable United States Pharmacopeia or National Formulary monograph. Failing that, the substance must be a component of an FDA-approved drug product, or appear on the 503A bulks list.
The order matters. The list is the third door, reached only when there is no monograph and the substance is not a component of an approved product. Most of the peptides sold in this market fail the first two, which is why the list is where their fate is decided.
Two further conditions apply regardless of which door a substance came through. The material must be accompanied by a valid certificate of analysis, and it must have been made by an establishment registered with FDA. Those are conditions on the pharmacy, and they are the reason a certificate exists in the first place.
The 503B gate is narrower
An outsourcing facility has fewer options. It may not compound a drug containing a bulk drug substance unless that substance appears on the 503B bulks list. The alternative is that the compounded drug appears on FDA's drug shortage list at the time it is compounded, distributed and dispensed.
The standard for the 503B list is different too. FDA describes it as a list of substances for which there is clinical need, a statutory term the agency published guidance interpreting in March 2019.
The certificate of analysis and registered-establishment requirements apply here as well, and so does compliance with a monograph where one exists.
What a nomination actually is
A nomination is a formal submission from a member of the public asking FDA to place a substance on one of the lists. Anyone may file one. Compounders, trade associations and manufacturers do.
FDA solicited nominations for the 503A list in 2015 and has been working through them since. The package a nominator submits is what the agency evaluates, so the quality of the file determines how far it gets.
That is why nomination packages appear so often in the record for individual peptides. A missing certificate, a certificate for the wrong salt form, or an unclear statement of which substance is meant are defects in the submission rather than in the molecule. They stop the evaluation just as effectively.
A nomination can also be withdrawn by the person who filed it. When that happens, FDA may still evaluate the substance on its own initiative.
The three interim categories
While the evaluation runs, FDA operates an interim policy so that patient treatment is not disrupted. It sorts nominated substances into three categories, and the labels are widely misread.
Category 1 holds substances nominated with enough supporting information to evaluate, that appear on no other list. FDA states it does not intend to take action against a compounder using them, provided the conditions in the guidance are met.
Category 2 holds substances FDA has identified significant safety risks for, pending further evaluation. They are outside the category 1 policy, and FDA says it would consider taking action against a compounder using them under its general enforcement policies.
Category 3 holds substances nominated with insufficient supporting information to evaluate. They can be re-nominated with a better package. They are not eligible for the category 1 policy either.
Category 2 is not a finding that a molecule is dangerous
The category 2 page is where this gets misread most often, and reading the entries themselves is the cure.
Some entries describe genuine documented harm. The cesium chloride entry cites reports of serious heart problems in humans. The diethylstilbestrol entry cites cancers. Those are findings.
Most of the peptide entries say something different. For KPV, FDA writes that it has not identified any human exposure data by any route and lacks the information needed to know whether the drug would cause harm. For epitalon, that it has not identified safety-related information for the proposed route. For the thymosin beta-4 fragment sold as TB-500, the same.
The recurring phrase across these entries is that the agency lacks sufficient information. An information gap and a harm finding are different things, and they are printed in the same table. The honest reading is the one FDA wrote: nobody knows, and nobody has measured.
What the peptide entries share
Read across the peptide entries and the same technical concern appears again and again: risk of immunogenicity for certain routes of administration, because of the potential for aggregation and peptide-related impurities.
That is a manufacturing and characterization concern, not a claim about pharmacology. Peptide molecules that clump can provoke an immune response, and impurity data is what would let anyone judge how likely that is.
A few entries add a specific complication. The GHRP-2 and ipamorelin acetate entries note that those peptides contain unnatural amino acids, which make the substance harder to characterize. The ipamorelin entry also cites a published study reporting serious adverse events, including death, when ipamorelin was given intravenously to improve gastric motility. FDA adds that it has not identified safety information for certain other injectable routes.
How to read the two tables on that page
The safety-risks page carries two tables and they mean different things.
The first lists substances currently in category 2 under the 503A policy, the 503B policy, or both, each with the date it was added and a summary of the identified risk. As of the April 2026 version of the page, it holds 14 substances. Ipamorelin acetate is the peptide on it, under 503B.
The second lists substances previously in category 2 whose nominations were withdrawn by the nominators. It holds 17 substances, and it reads like a catalog of the peptide market. AOD-9604, BPC-157, cathelicidin LL-37, CJC-1295, emideltide, epitalon, GHK-Cu for injectable routes, KPV, melanotan II, MOTS-c, selank, semax, thymosin alpha-1 and the TB-500 fragment are among them.
A withdrawn nomination is not an approval and not a rejection. It means the person who asked stopped asking.
Where the advisory committee fits
FDA consults the Pharmacy Compounding Advisory Committee as it evaluates nominations. The committee provides advice on scientific, technical and medical issues concerning compounding under sections 503A and 503B, and makes recommendations to the Commissioner.
It is an advisory body of twelve voting members including the chair, drawn from compounding, pharmaceutical manufacturing, pharmacy and medicine, with representation from the National Association of Boards of Pharmacy and the United States Pharmacopeia.
A committee recommendation is a recommendation. Placing a substance on a list happens through notice-and-comment rulemaking, which is a separate and slower process. FDA issued a final regulation in February 2019 placing six substances on the 503A list, and a proposed regulation in September 2019 covering thirty-one more that has not been finalized.
The compound boards here carry the current position for each peptide with the date it was checked, which is the number that changes.
One recent change worth knowing
FDA has issued guidance revising how the interim policy is applied. Substances nominated on or after January 7, 2025 are not placed into the three categories at all.
Substances already in category 1 may stay within the interim enforcement policy until the agency decides on their inclusion, or removes them based on safety information. Nominations continue to be accepted and evaluated through the statutory process.
The practical effect is that the category system is closing behind the substances already in it. A peptide nominated today does not get a category, and that is a change in process rather than a judgment about the peptide.
Key takeaways
- Federal law limits compounders to bulk substances that clear a monograph, an approved-product component test, or a bulks list.
- Section 503A pharmacies and 503B outsourcing facilities have separate gates and separate lists.
- A nomination is a public submission asking FDA to add a substance, and its quality decides how far it gets.
- The interim policy sorts nominations into three categories, and category 2 covers identified safety risks.
- For most listed peptides, FDA's stated basis is missing information rather than demonstrated harm.
- Substances nominated on or after January 7, 2025 are no longer placed into those categories at all.
Frequently asked questions
What is a bulk drug substance?
The raw active ingredient a compounded medication is made from, as distinct from a finished drug product. Federal law limits which ones a compounder may use. Under section 503A a substance must comply with a USP or National Formulary monograph, or be a component of an FDA-approved drug product, or appear on the 503A bulks list. It must also come with a valid certificate of analysis and be made by an FDA-registered establishment.
Does being on a bulks list mean a peptide works?
No. The lists govern whether a substance may lawfully be used in compounding. They are not efficacy determinations and they are not approvals. An FDA-approved drug has been through a review of safety and effectiveness for a specific use; a substance on a bulks list has been through a different evaluation with a different question at its center.
What does it mean if a peptide is in category 2?
That FDA identified significant safety risks relating to its use in compounding, pending further evaluation, and that it sits outside the enforcement policy applied to category 1 substances. Reading the entry matters more than reading the label. For several peptides the stated basis is that FDA has not identified human exposure data and lacks the information needed to know whether the substance would cause harm. That is a gap rather than a finding of harm.
Who can nominate a substance, and what happens to it?
Anyone can. FDA evaluates the nomination package and consults the Pharmacy Compounding Advisory Committee. A nomination with insufficient supporting information lands in category 3 and can be re-nominated with a better package. A nomination can also be withdrawn by whoever filed it, and FDA may then evaluate the substance on its own initiative. Actually placing a substance on a list requires notice-and-comment rulemaking.
Why do so many peptide entries mention immunogenicity?
Because it is the structural concern with injecting a peptide whose impurity profile is unknown. Peptide molecules can aggregate, meaning clump together, and aggregates are the form most likely to provoke an immune response. Impurity limits and aggregate testing are the measurements that would let anyone judge that risk, and FDA repeatedly records that they were not supplied. A few peptides add a second complication by containing unnatural amino acids, which make characterization harder.
Sources
Each document below is named as it names itself, with the date printed on that document rather than the day it was read.
- Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act — U.S. Food and Drug Administration, May 2026
- Bulk Drug Substances Used in Compounding Under Section 503B of the FD&C Act — U.S. Food and Drug Administration, January 2025
- Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks — U.S. Food and Drug Administration, April 2026
- Pharmacy Compounding Advisory Committee — purpose and membership — U.S. Food and Drug Administration, July 2025
- Compounding and the FDA: Questions and Answers — U.S. Food and Drug Administration, September 2025