Draft standard CEI-MS-03: Determination of peptide content… — submissions
The 11 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
11 submissions were received. Each is published in full below with its declared interest, the secretariat response and the disposition. The Institute publishes submissions it did not accept in the same form as those it did.
A superseded version should remain reachable from the version that replaced it
Having read the draft of CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity, the respondent puts one point to the secretariat.
The respondent states that the draft supersedes an earlier document and that a reader who cited the earlier version has no way to reach it from the new one, which makes it impossible to see what changed.
The respondent asks that every version carry a link both to what it supersedes and to what supersedes it.
The secretariat notes this submission. The corrections and versioning policy already requires bidirectional version links and every superseded document is retained at its own address.
No amendment arises. The requirement is stated in the corrections and versioning policy and the amendment log of this document links to the version it replaced. The respondent is correct that the link was absent from the draft page furnished for consultation, which was a defect of the consultation copy and not of the policy.
A determination does not record the version of the standard it was made under
The respondent read the draft of CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity and has confined this submission to a single requirement.
The respondent states that the standard will be revised and that results reported under different versions will circulate together, indistinguishable from one another.
The respondent proposes that the standard identifier and version be carried on the face of every determination.
The secretariat accepts this submission. A conformance claim against an unspecified version is not a conformance claim.
Every determination reported under this standard now carries the standard identifier and version on its face, and a claim of conformance that does not identify the version is recorded by the Institute as not conformant.
The standard permits a purity figure to be described as an assay
The draft of CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity was read from the standpoint of a laboratory that assigns content against a reference material.
The terms are used interchangeably in the draft. They are different quantities: one is the proportion of the chromatographic response attributable to the principal peak, the other is the mass of the named substance per unit mass of the preparation. A certificate that reports the first under the name of the second overstates content by the mass of counter-ion and water.
The respondent proposes that the two be defined separately in the terminology section and that the standard prohibit the second term being used for the first.
The respondent supports submission 001 so far as it goes and adds the matter set out here.
The secretariat accepts this submission. The conflation is the commonest arithmetic error in this supply channel and the standard should not license it.
The two quantities are now separately defined and the standard states that a chromatographic purity may not be reported as an assay result.
Nothing in the standard addresses transfer of the method between laboratories
The respondent notes that a stated vial mass may be substantially counter-ion and water, and submits with that in view.
The respondent states that determinations under this standard will be performed by different laboratories on the same material and that without transfer criteria their results are not comparable.
The respondent proposes a transfer protocol with acceptance criteria for inter-laboratory agreement.
The secretariat accepts this submission in part. Acceptance criteria for agreement between laboratories are added. A full transfer protocol is not, because transfer is a quality-system activity rather than a determination and the series does not address quality systems.
The standard now states the maximum difference between laboratories analysing the same sample at which results are treated as agreeing, and requires that a comparison across laboratories state whether that criterion was met.
The preparation solvent is not specified and changes what is measured
The respondent has read CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity in draft and makes one submission.
Material that has aggregated will dissolve to different extents in different solvents, so a preparation in one solvent can report a purity that a preparation in another does not reproduce, on the same vial.
The respondent proposes that the preparation solvent be specified rather than left to the laboratory.
The secretariat accepts the reporting requirement and declines to specify a single solvent across all materials in scope.
The preparation solvent is now a required reporting field and the procedure names an acceptable range. Specifying one solvent for every material in scope would exclude compounds the standard is intended to cover.
A single method cannot support the conclusion the standard permits
The respondent’s comment on the draft of CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity arises from applying it to hygroscopic material in ordinary laboratory conditions.
The respondent states that species invisible to this determination will not appear in the result, and that a conclusion about the material as a whole requires an orthogonal method.
The respondent proposes that an orthogonal determination be mandatory.
The secretariat accepts this submission in part. An orthogonal determination is required where a conclusion about the material as a whole is to be drawn. It is not required where the standard is used to report the quantity it measures.
The standard now distinguishes a determination of the measured quantity, which stands alone, from a conclusion about the material, which requires a named orthogonal determination, and states that the second claim made on the strength of the first alone is not conformant.
The limitations section states what the method cannot do but not what a reader will wrongly conclude
This submission addresses the draft of CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity from the standpoint of a laboratory that performs the determination routinely.
The limitations section is accurate and abstract. The respondent states that the misreadings this standard should prevent are specific and predictable, and that naming them would be more use than a general statement of scope.
The respondent proposes that the limitations section list the specific inferences a conformant result does not support.
The respondent notes submission 001 above and does not repeat the ground it covers.
The secretariat accepts this submission. A limitation stated abstractly is a limitation a reader will not apply to the case in front of them.
The limitations section now lists the specific conclusions a conformant determination does not support, each stated as a sentence a reader could otherwise have written, and the list is placed before the references rather than in an annex.
The document set should be published in translation
The respondent submits on CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity, on a matter that is not specific to this draft but is visible in it.
The respondent notes that the assessments concern compounds supplied internationally and that publishing only in English restricts access to the assessment to readers who work in it.
The respondent proposes machine translation of the document set as an interim measure, with human review of the certainty language.
This point is adjacent to the one made in submission 007 and the respondent puts it in a form the secretariat can act on.
The secretariat does not accept this submission, and records that the underlying point is sound and that the proposed remedy is the difficulty.
A translation whose certainty language has drifted is a different assessment carrying the Institute's name, and the Institute cannot review translations it does not have the capacity to review. The documents remain in English. The submission is published in full because the access problem it identifies is real and unresolved.
A single determination is permitted where duplicates would be inexpensive
This is a submission on CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity.
The respondent states that the draft permits a result to be reported from one injection, and that the marginal cost of a duplicate is small relative to the value of detecting a preparation error.
The respondent proposes that duplicate determinations be mandatory.
The respondent’s submission overlaps with submission 001 and was prepared without sight of it.
The secretariat accepts this submission in part. Duplicate preparation and injection are required, and a criterion for agreement between them is stated. The proposal to require full duplicate sample preparation on separate days is declined as disproportionate.
The standard now requires duplicate preparation and injection with a stated maximum difference between the two, and requires that a difference exceeding it be investigated before any figure is reported.
The draft prescribes a procedure where it should state performance
The respondent submits on the draft of CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity. Content is the determination that turns a purity percentage into a mass of peptide, and it is the determination most often absent from a certificate.
Several clauses specify a gradient, a column chemistry and a temperature. The respondent states that fixing these prevents a laboratory from using a validated equivalent, and that the Institute settled on stating performance when it scoped the series.
The respondent proposes that the prescriptive clauses be converted into performance requirements with the prescribed conditions retained as a worked example.
This submission is made in the same spirit as submission 005 and on a different aspect of the draft.
The secretariat accepts this submission. The draft departed from the position settled when the series was scoped, and the departure was not deliberate.
The prescriptive clauses are converted to performance requirements, the specific conditions are retained as a worked example clearly labelled as one, and a laboratory using a different validated procedure that meets the stated performance reports a conformant determination.
The standard does not state that a determination on one unit says nothing about the batch
This submission concerns the draft standard CEI-MS-03, Determination of peptide content and its distinction from chromatographic purity. The respondent’s interest is in mass balance and in what a certificate has to carry before one can be formed.
The respondent states that determinations under this standard are generally performed on a single unit and that certificates then travel with every unit of a batch, so that a single-unit result is routinely read as a batch result.
The respondent proposes that the standard require a sampling statement on the face of every determination.
The respondent read submission 006 after drafting this one and has not altered it, the two points being distinct.
The secretariat accepts this submission. The inference from unit to batch is the most consequential unstated assumption in supply documentation.
Every determination made under this standard now carries a sampling statement recording how many units were sampled, from what population and by what plan, and the standard states that a determination on a single unit supports no inference about any other unit.
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- International Organization for Standardization. ISO/IEC 17025:2017 General Requirements for the Competence of Testing and Calibration Laboratories. ISO/IEC Standard 2017;3rd edition. identifier not held by the Institute
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.