Evidence review
Certificates of Analysis: What They Prove
A COA is a claim about a lot, not a guarantee about a vial. What each test answers, what a purity figure cannot say, and the gap the document never closes.
What the document is
A certificate of analysis is a record from a manufacturer or a testing laboratory stating the results of specified tests on a specified lot, against specified acceptance criteria.
Three words in that sentence are doing all the work: specified, lot, and criteria. A certificate with no named method, no lot number, or no acceptance criterion is a marketing artefact wearing a lab coat.
Where a certificate is actually required
In the compounding framework it is not optional, and it does not stand alone.
FDA states that bulk drug substances used in compounding must be accompanied by a valid certificate of analysis and must have been manufactured by an establishment registered with FDA under section 510 of the FD&C Act. The requirement is written as a pair, on both the 503A side1 and the 503B side2.
That pairing is the whole lesson. The regulation does not treat a certificate as sufficient. It treats it as one of two conditions, the other being that a known, registered establishment made the material. A certificate accompanying a substance from an unregistered manufacturer does not satisfy the requirement, however impressive the document looks. The two compounding schemes are set out in 503A vs 503B.
The tests, and what each answers
Appearance and solubility — is it the right kind of solid, and does it dissolve as expected. Low information, but a fast failure.
Identity — is this the intended sequence. Answered properly by mass spectrometry, and by amino acid analysis or sequencing. Not answered by a chromatogram.
Purity — what proportion of the material is the intended compound rather than related substances.
Water content and residual solvents — how much of the vial's mass is not peptide.
Counter-ion content, usually acetate or trifluoroacetate — again, mass in the vial that is not peptide.
Sterility and bacterial endotoxin — required for anything injected, and tested on the finished sterile preparation rather than on a bulk powder.
Peptide content — the fraction of the weighed mass that is actually peptide, after water and counter-ion are subtracted. This is the number that determines how much active material a given weight contains, and it is frequently missing.
What "98% purity by HPLC" does and does not say
It says that under one chromatographic method, with one detector, 98% of the detected peak area eluted as the main peak.
It does not say the main peak is the intended sequence. That is an identity test, and a closely related wrong sequence can co-elute or elute nearby while looking clean.
It does not account for anything the detector cannot see. Ultraviolet detection responds to certain structures; material without them is invisible to it.
It does not tell you how much of the vial is peptide. A 98%-pure powder that is 20% water and counter-ion by mass is 98% pure and contains substantially less peptide than the label weight implies.
It does not measure aggregation, which is the property FDA repeatedly names for this class.
The tests that are usually absent, and why that matters here
Read FDA's published notes on the peptides nominated for use in compounding and one concern recurs almost verbatim across entry after entry: compounded drugs containing the substance may pose a risk for immunogenicity for certain routes of administration due to the potential for aggregation and peptide-related impurities, with added complexity in characterising the active ingredient3.
For the thymosin beta-4 fragment the agency goes further, stating it has not identified any human exposure data for drug products containing it3.
Now compare that concern with a routine certificate. Identity, HPLC purity, water, acetate — none of those measure aggregation. The specific risk the regulator has named is not among the tests the document reports. That is not a flaw in the document. It is a mismatch between what is measured and what is worried about, and it is invisible unless you hold the two lists side by side. Our TB-500 page covers what else is missing from that compound's file.
The gap the certificate cannot close
A certificate describes a lot that was tested. A buyer holds a vial. Between them sit several steps the document says nothing about.
Whether this vial was filled from that lot.
Whether the material was re-handled, re-weighed or re-packaged after testing.
Whether the finished preparation is sterile — a bulk-substance certificate is not a sterility release for a filled vial.
Whether the peptide survived shipping. FDA has noted complaints of compounded GLP-1 products arriving warm or with inadequate ice packs, and advises against using an injectable GLP-1 drug that arrives warm4.
Whether the document itself is genuine. This is not a hypothetical: FDA has stated that it is aware of fraudulent compounded semaglutide and tirzepatide with false information on the product label, in some cases naming compounding pharmacies that do not exist, and in other cases naming a licensed pharmacy that FDA's information indicates did not compound the product4.
If a pharmacy name on a label can be fabricated, a laboratory name on a PDF can be too.
What has been found when someone checked
An analytical study of misbranded and adulterated drugs sold over the internet examined material sold as TB500 and TB1000 and reported that the content is not systematically consistent with the products' own former descriptions5.
And inside the regulated tier, a study of FDA inspection reports for outsourcing facilities registered between January 2020 and April 2025 found that each of the 11 facilities inspected out of 48 registered had at least two significant objectionable findings, with recurring themes including inadequate sterility testing, unvalidated production processes and deficient recordkeeping6.
So neither the presence of a certificate nor the presence of an inspection regime settles the question by itself.
How to read one in ninety seconds
Find the lot number, and check it against the vial rather than the listing.
Find the date, and check it against the material's stated shelf life.
Check that identity was determined by mass spectrometry, not inferred from a chromatogram.
Check whether peptide content is reported, or whether the certificate reports purity alone.
Check that each test names a method and an acceptance criterion, and that the result is compared against the criterion rather than simply printed.
Check who issued it and whether that party is independent of the seller.
If the document names no methods, no criteria and no lot, it is not evidence about anything.
The honest summary
A certificate of analysis is a claim, made by a named party, about a lot of material, on a date, using stated methods. That is genuinely worth something — a claim with a name attached is better than no claim.
It is not proof that the vial in your hand contains what the label says, in the amount stated, in a form that has not aggregated, sterile, and unchanged by its journey. No document of that type can be. The absence of one is a hard stop; the presence of one is the beginning of the question, not the end. Where that leaves an unapproved compound is set out in what "research chemical" actually means.
Frequently asked questions
Does a certificate of analysis prove a peptide is safe?
No. It reports specified tests on a specified lot. In the compounding framework FDA requires a valid certificate of analysis together with manufacture by an establishment registered under section 510 of the FD&C Act — the certificate is one of two conditions, never a standalone assurance.
What does 98% purity by HPLC actually mean?
That under one chromatographic method with one detector, 98% of the detected peak area eluted as the main peak. It does not confirm the peak is the intended sequence, does not account for material the detector cannot see, does not tell you what fraction of the vial's mass is peptide rather than water and counter-ion, and does not measure aggregation.
Why does aggregation matter?
Because it is the risk FDA names most often for this class. Its published notes on peptides nominated for use in compounding repeatedly cite possible immunogenicity risk from aggregation and peptide-related impurities, plus complexity in characterising the active ingredient. A routine identity-and-purity certificate does not test for it.
Can a certificate of analysis be faked?
The surrounding documents demonstrably can be. FDA has stated it is aware of fraudulent compounded semaglutide and tirzepatide bearing false label information, in some cases naming compounding pharmacies that do not exist and in others naming a licensed pharmacy that FDA's information indicates did not compound the product.
References
- U.S. Food and Drug Administration (2026). Bulk Drug Substances Used in Compounding Under Section 503A of the FD&C Act. FDA.gov. https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503a-fdc-act
- U.S. Food and Drug Administration (2026). Bulk Drug Substances Used in Compounding Under Section 503B of the FD&C Act. FDA.gov. https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503b-fdc-act
- U.S. Food and Drug Administration (2026). Category 2 of the Bulk Substances Nominated Under Sections 503A or 503B of the Federal Food, Drug, and Cosmetic Act. FDA.gov. https://www.fda.gov/drugs/human-drug-compounding/safety-risks-associated-certain-bulk-drug-substances-nominated-use-compounding
- U.S. Food and Drug Administration (2026). FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. FDA.gov. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/medications-containing-semaglutide-marketed-type-2-diabetes-or-weight-loss
- Delcourt V et al (2023). TB500/TB1000 and SGF1000: A scientific approach for a better understanding of misbranded and adulterated drugs. Drug Test Anal. https://pubmed.ncbi.nlm.nih.gov/36482504/
- McCall KL et al (2026). A quantitative and qualitative study of US FDA inspection reports of 503B outsourcing facilities. J Am Pharm Assoc. https://pubmed.ncbi.nlm.nih.gov/42242462/
Medical disclaimer: This content is for general educational purposes only and is not medical advice, diagnosis, or treatment. Always consult a licensed healthcare professional before starting, stopping, or changing any treatment.
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