What the COA itself states: note 1
Condition 3 asks for "a valid certificate of analysis (COA) that includes test results consistent with existing guidance-based criteria described by FDA (see Appendix B)." The policy gives the reason: "This helps provide assurance that what a compounder receives from a supplier is what it claims to be and has been tested for identity, purity, potency, and the absence of harmful contaminants such as endotoxins, heavy metals, microbial contamination, and impurities."
Note 1 opens: "Required active pharmaceutical ingredients (APIs) and Manufacturer(s) information includes:" The left column below is its list, line by line, numbered as on the certificate at the top of this page. The right column is our reading of what each line looks like on a COA that answers it.
| Note 1 asks for | What we look for |
|---|---|
| Bulk drug substance (BDS) name (e.g., USAN, INN, IUPAC) | The name of one of the six, in the form Appendix B names. |
| Chemical structure, amino acid sequence, molecular formula, molecular weight | Each one matching Appendix B for that peptide, salt form included. |
| Manufacturer's corporate name, its FDA Establishment Identification (FEI) number, address | The company that made the API, its FEI number and the plant's address. Condition 4 asks for the plant's physical location on the COA. |
| Any firm involved in processing (i.e., purification, sterilization, sizing, milling, etc.), FEI number, address | Each such firm, with its own FEI number and address. |
| Repacker or reprocessor, the laboratory that performed the analysis, if applicable | Named whenever the lot passed through one, or was tested somewhere other than the plant. |
| Batch number | The same number as on the container label and the paperwork that came with it. |
| Date of synthesis | Present, and before the date of release. |
| Date of release | Present. |
| Expiration date and/or retest date | Present, and not yet passed when the lot arrives. |
| Grade: "Intended for human drug compounding" | Stated in those words. |
| Dosage form: a statement of purpose (i.e., intended dosage form, such as injectable, oral, etc.) | A dosage form Appendix B covers for that peptide. |
| Storage conditions | Present. |
| Statement of compliance: (e.g., "This product was manufactured and tested in compliance with CGMP.") | A CGMP statement. |
| Dated and signed by authorized personnel of the quality unit(s) and identify the original manufacturer | A date and a signature from the manufacturer's quality unit. |
For the manufacturing itself, note 1 points to ICH Q7: CGMP guidance "should be sourced from the ICH guidances for industry Q7: Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (November 2020) and the Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients: Questions and Answers (April 2018)."
The tests: the policy's table
Appendix B's testing standard is a table of 20 tests. The test names, qualifiers and references below are the policy's; the methods are shortened. The policy cites USP chapters by number and we do the same. We do not reproduce USP text.
| Test | Method, in short | Criteria and references |
|---|---|---|
| No qualifier in the table 13 tests | ||
| Physicochemical properties | Orthogonal methods (Table 1) | Comply. ICH Q6A |
| Identification / primary sequence | Orthogonal methods (Table 1) | Comply with ICH Q6A for identification; "verified to be the BDS listed in this guidance". USP <1503> |
| Assay (drug substance) | HPLC or RP-HPLC against an established quantitative reference standard | Comply. USP <621> |
| Immunoassay | In vitro adaptive and innate immunogenicity assays; ELISA; surface plasmon resonance | Comply. The FDA's 2014 guidance on immunogenicity assessment for therapeutic protein products |
| Peptide content (net) | Amino acid analysis, nitrogen analysis, UV spectroscopy or qNMR | Comply. USP <1052>, <507>, <461>, <197>, <857>, <761>, <1761> |
| Peptide-related impurities | Orthogonal methods (Table 1): individual specified, any unspecified, and total impurities | Comply with ICH Q3A. USP <1503> |
| Residual solvents | Gas chromatography | Comply with USP <467>, ICH Q3C(R7) |
| Elemental impurities | ICP-MS | Comply with USP <232>, <233>, ICH Q3D(R1). USP <1065> |
| Residual TFA | Ion chromatography | Comply. USP <503.1>, <1065> |
| Residual fluoride | Ion-selective electrodes | Comply. USP <1065> |
| Water content | Karl Fischer titration | Comply. USP <921> |
| Counter-ion content | Acetate; other anions and cations | Comply. USP <503>, <1065> |
| Nitrosamine impurities | Small-molecule nitrosamines, with no qualifier; and NDSRIs "when applicable (in the presence of secondary, tertiary, or quaternary amines)" | The CDER nitrosamine acceptable intake limits, and the FDA's two nitrosamine guidances |
| Tied to injectable forms by note 4 2 tests | ||
| Bioburden | Microbial enumeration; specified microorganisms | Comply with <1111>. USP <61>, <62> |
| Bacterial endotoxins | Bacterial endotoxins test (for example, LAL testing) | Comply with USP <85> |
| With a qualifier in the table 5 tests | ||
| Higher order structure | Orthogonal methods (Table 1) | For complex peptides of 8 amino acids or more. USP <1503> |
| Aggregates | Orthogonal methods (Table 1) | For complex peptides of 8 amino acids or more. USP <1503> |
| Biological activity / bioassays | Orthogonal methods (Table 1) | For complex peptides of 8 amino acids or more. USP <1503> |
| Host cell-related impurities | Orthogonal methods (Table 1) | For a recombinant product |
| Thiol groups | Ellman's test; LC-MS | Required only if cysteine is present. USP <736> |
Table 1, at the end of Appendix B, lists the methods the policy accepts as orthogonal for each attribute. For identification it asks for "100% sequence coverage" and lists methods such as HPLC coelution with a reference standard, mass spectrometry for monoisotopic mass, amino acid analysis, tandem mass spectrometry sequencing and NMR.
Which rows apply to which peptide turns on the qualifiers: the number of amino acids, whether the peptide is a salt, the dosage form, and how it was made. Each peptide's page works that out: BPC-157, Epitalon, KPV, MOTS-c, Semax and TB-500.
How each result is identified: notes 2 to 4
A result alone does not answer Appendix B. The notes ask the COA to say how each test was run.
Note 2, the method. "Analytical testing may be conducted utilizing either established compendial procedures or appropriately validated non-compendial (in-house) procedures." Each COA "should identify the analytical method used, including the test method name, test method number", and the document number of the method's validation report (for in-house methods) or verification report (for compendial methods). "The COA should also include information on any reference standards utilized during testing."
Note 3, two methods. "Orthogonal analytical methods consist of at least two independent analytical procedures relying on distinct physicochemical principles, which should be utilized to provide robust characterization of the BDS."
Note 4, the dosage form. Bioburden and bacterial endotoxins are "Critical Quality Attributes (CQAs) specific to injectable dosage forms". "If the BDS is intended for incorporation into an alternative dosage form, the appropriate quality tests specific to that dosage form should be conducted and the results reported on the COA."
On a COA, in our reading, that means a method number and a report number beside each result, two identification methods that rest on different principles, and the reference standard named.
The request to your supplier
The fastest way to a COA that answers Appendix B is to ask for one before the order. This is the email we would send.
The request, ready to sendAppendix B, notes 1 to 3; condition 4
Subject: COA for [peptide], lot [number], before we order
Hi [name],
Before we place our order for [peptide], could you send the COA for the exact lot you'll ship? We need it to show:
- The original manufacturer's name, FEI number and plant address, not only yours if you didn't make it.
- The grade "Intended for human drug compounding," the intended dosage form, and a CGMP statement.
- Identity confirmed by two independent methods, and for each test, the method number and its validation or verification report number.
- A date and signature from the manufacturer's quality unit.
If you bought this lot from another company, please also send your documented validation of that manufacturer and of its COA.
Thanks,
[your name]
Where the policy stands
As of November 11, 2026.
HHS announced the policy in the Federal Register on October 30, 2026, in FR Doc. 2026-22192. The notice says "HHS is announcing the availability of a draft" policy, and that "Written comments can be submitted until 2 weeks after date of publication in the Federal Register via regulations.gov on Docket No. HHS-OASH-2026-0496". It also says the policy "does not establish any rights for any person and is not binding on HHS or the public."
The policy calls itself an interim policy, and says: "HHS may revisit application of this interim policy (in whole or in part) if, among other things, a safety signal or product quality issue arises with a compounded drug product within the scope of this policy."
It does not put the six peptides on the 503A bulks list. The notice says the FDA's future rulemakings "may propose adding some or all of these peptides to the 503A bulks list based on the available evidence." For the current text, the notice points to the HHS website "to find the most current version of the policy."
Sources
Every source below was opened and read for this page. Last reviewed: November 11, 2026.
- HHS Enforcement Discretion Policy Regarding 503A Compounding Using Certain Peptide Bulk Drug Substances. The policy, with Appendix A (the six peptides) and Appendix B (their identities, the dosage forms it covers and the testing standard). 16 pages. PDF. Quotations not otherwise marked come from it.
- Notice of availability, FR Doc. 2026-22192. HHS, Office of the Secretary. Federal Register, Volume 91, Number 209, pages 68526 to 68527, October 30, 2026. Docket No. HHS-OASH-2026-0496. Quotations marked as the notice's come from it.
We read documents. We do not test material.