Writing a peptide specification annex

“Semaglutide, ≥98%” is a product description, not a specification. This is the field list that turns it into something a laboratory can test and a supplier can be held to — including the three ambiguities that cause most arguments.

Why the annex is the technical document

A purchase contract says what happens if material fails. The specification annex says what “fail” means. If the annex is thin, the contract has nothing to enforce, and every disagreement becomes a negotiation about intentions. The annex should be short enough to read in five minutes and specific enough that two laboratories testing the same lot reach the same verdict.

1. Identity block

Field	What to state
Product name	The name you will use on the label, plus any synonym the supplier uses — aliases are a common source of mismatch
Sequence	One-letter code, N→C direction stated, with every non-standard residue and terminal modification written out
Molecular weight	The value and whether it is monoisotopic or average; state the calculated value from the sequence, not only the catalogue figure
CAS number	Where one exists. A CAS number identifies a substance, not a grade, and does not substitute for the sequence
Counter-ion form	Acetate, TFA, HCl, or “as free base”; if a mixture is acceptable, state the ratio or the limit
Appearance	Colour and form of the lyophilized cake or powder; add the appearance of the reconstituted solution if you will rely on it

Identity is the one block where “report” is not good enough. If the annex does not fix the sequence and the salt form, a supplier can ship a materially different molecule that passes every purity limit you wrote. The arithmetic behind sequence-to-mass is covered in sequence and molecular weight; when an intact mass is not enough, MS/MS confirmation is the test to specify.

2. Purity and assay block

This is where most annexes fail, because “purity” is used for at least three different measurements:

Chromatographic purity (area %) — the target peak as a fraction of UV-absorbing peak area, at a stated wavelength, on a stated method.
Assay or net peptide content — the mass fraction of the peptide itself, excluding counter-ion, water and residual solvent.
Impurity profile — individual and total specified impurities, each with its own limit.

A limit of “≥98%” without naming which of these it refers to is not testable. Write the method into the annex: column chemistry and dimensions, mobile phases, gradient, detection wavelength, injection concentration, integration rules and the system-suitability criteria. If the method is the supplier's in-house method, attach the summary; if it is a pharmacopoeial method, cite the monograph and edition. The difference between area percent and mass percent is worked through in reading a chromatogram.

3. The basis-of-calculation problem

The same lot can be “99%” or “82%” depending on the denominator. Three bases are common and they are not interchangeable:

Basis	Denominator	Typical use
As-is	Everything in the vial, including water and counter-ion	Weighing and shipping; what you actually receive
Anhydrous	Everything except water	Comparing lots where moisture varies
Peptide base	The peptide moiety only, counter-ion excluded	Molar calculations and cost-per-mg comparisons

Put the basis in the annex, next to the number. Then put it in the certificate template too, so the release value and the specification are expressed the same way. A supplier who reports “98.5%” without a basis has told you less than they appear to. The cost consequence is covered in net peptide content and cost per mg.

4. Physical and chemical block

Field	Method	Why it belongs in the annex
Water content	Karl Fischer	Affects stability, weighing and the as-is basis
Residual organic solvents	Headspace GC, where relevant	Purification residues change handling and smell; some are regulated — see residual solvents
pH of reconstituted solution	Stated concentration and solvent	A release check that also predicts handling behaviour
Solubility	Stated solvent and concentration	“Freely soluble” without conditions is not a criterion
Endotoxin / bioburden	LAL / microbial count	Only if actually performed — never list a limit you do not intend to test
Heavy metals / elemental impurities	ICP-MS or compendial method	Relevant where catalysts or metal handling are part of the route

The endotoxin row deserves emphasis: listing a limit implies a test. If the annex says “endotoxin ≤ X EU/mg” and the certificate never reports it, you have created an unverifiable requirement — worse than omitting it, because it looks controlled. What each test can and cannot show is set out in endotoxin and bioburden and testing methods.

5. Fill, packaging and labelling block

The annex should fix the container closure and the fill, not leave them to the order confirmation. At minimum: primary container and material, nominal fill with tolerance, headspace treatment, desiccant, secondary pack, and the label content for every layer. Packaging choices and their failure modes are covered in packaging configurations.

6. Sampling, retention and documentation

State the sampling plan — how many containers, how the sample is drawn, who holds it — and require a retained sample from the same lot for an agreed period. Then list the documents that must accompany each shipment: certificate of analysis per lot, specification sheet, safety data sheet, packing list and commercial invoice. Make the annex reference the document numbers so a shipment can be checked against it without interpretation.

7. Common omissions that make a limit unenforceable

No method. A numeric limit without a method is a preference.
No basis. As-is, anhydrous or peptide base — unstated means the supplier chooses, and they will choose the flattering one.
No impurity limits. Total purity can pass while a single specified impurity is far above what your work tolerates.
No units on microbiological limits. EU/mg, EU/mL and EU per vial are different specifications.
No revision control. An undated annex cannot be referenced in a dispute; give it a version, an effective date and a change log.
No acceptance criteria for appearance of solution. Visible particles, colour and clarity are cheap to specify and hard to argue about later.
No reference standard. If purity is measured against an in-house standard, say what it is and how it was qualified.
Contradiction with the certificate template. If the annex asks for water content but the certificate has no field for it, the requirement will quietly disappear.

8. Keep it alive

A specification annex is a controlled document. Give it a revision number, date every change, and route changes through the same change-control clause as the supply agreement — otherwise a “minor” edit to a limit becomes a silent renegotiation. Review it after the first three lots: the values you wrote before you had data are hypotheses, and the first real certificates are the evidence. If a limit turns out to be unmeasurable at your scale, fix the annex rather than tolerating a permanent deviation.

This is a technical drafting checklist, not legal advice. Have the annex reviewed together with the supply agreement under the governing law, and confirm destination import requirements separately.

For laboratory research use only. This article describes specification practice; it makes no claim about any specific compound and does not support administration to humans or animals.

Editor's take

If it is not in the annex, it is a preference. Acceptance criteria turn 'we expect 98%' into a test a third party can apply — and that is the difference between a standard and a hope.

Sources & evidence

Specification and analytical expectations: ICH Q6B / Q2(R1) — ICH quality guidelines.
API manufacturing quality systems: ICH Q7 — same ICH page.
Chinese national standards: GB/T via the SAMR full-text platform.

Commercial due diligence guidance, not legal advice; supplier claims must be verified against batch documents.

Limitations

This is commercial due diligence guidance, not legal advice. Supplier claims must be verified against batch documents and, where required, an independent audit.