Draft certificate-of-analysis minimum data standard — submissions
The 13 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
13 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.
Nothing prevents a chromatogram being reprocessed until it passes
This is a submission on the draft of CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations, made by a respondent who assesses supplier documentation professionally.
Integration parameters can be adjusted after acquisition, and nothing in the draft requires the sequence of processing to be recorded. A result presented as a single determination may be the last of several.
The respondent proposes that the standard require an audit trail of processing, retained with the primary data.
The secretariat accepts the principle and adopts a narrower requirement.
The standard now requires the processing method and its version to be recorded with every result and the primary data to be retained. A full audit trail is recommended and not required, since it depends on software many laboratories in scope do not run.
A conformance claim is not defined and will be made loosely
The respondent has read CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations in draft and makes a single submission.
The respondent states that the draft nowhere defines what it means for a determination to conform, and that in the absence of a definition the phrase will be applied to determinations that meet some of the requirements.
The respondent proposes an explicit definition and a requirement that partial conformance be described as such.
The secretariat accepts this submission. An undefined conformance claim is a marketing phrase.
Conformance is now defined as meeting every requirement classified as critical together with the stated system suitability criteria, partial conformance must be described by naming the requirements not met, and a claim of conformance made without the sampling statement is not conformant.
The additional determinations required would materially increase release testing cost
This submission concerns CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations and makes one point.
The submission is made on behalf of a manufacturer. It states that the draft adds two determinations to those in existing compendial practice, and estimates the additional analytical burden per batch.
The submission does not dispute the analytical reasoning and asks that one of the two be made conditional rather than universal.
The secretariat accepts this submission in part. One determination is made conditional on a stated risk factor. The other is retained because the evidence supplied by the respondent does not bear on whether it is necessary, only on what it costs.
One of the two determinations is now required only where the stated risk factor is present, with the factor defined in the scope, and the other is retained as a universal requirement with the reasoning stated. The submission is identified as an industry submission.
Absence of evidence is presented in a form a reader will take as negative evidence
The respondent submits on the draft of CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations. A documentation standard is the one standard whose failure a purchaser can detect without a laboratory, which makes it the most consequential of the series.
Where the Institute has identified no study, the draft states that no evidence was found. In several places that sentence sits immediately after a paragraph describing an adverse outcome, and the juxtaposition invites the reading that the compound was studied and found wanting.
The respondent proposes a standing formulation, used identically wherever the situation arises, distinguishing an outcome that was studied and not demonstrated from an outcome that has not been studied at all.
This submission should be read alongside submission 002, which arises on the same draft.
The secretariat accepts this submission. The two states are different, they support different decisions, and the draft rendered them in language a reader could not reliably separate.
A standing formulation has been adopted and is applied wherever an evidence gap is recorded, distinguishing an outcome assessed and not demonstrated from an outcome not assessed. The formulation is identical at every occurrence so that it can be recognised at a glance.
The draft prescribes a procedure where it should state performance
The respondent submits on CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations, on a matter that is not specific to this draft but is visible in it.
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.
The respondent has read submission 001 and puts a further matter to the secretariat.
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 should state a pass limit
The respondent’s comment on the draft of CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations arises from handling certificates of this kind in practice.
The respondent states that a standard which reports a figure without a limit leaves the reader without a criterion, and that suppliers will set their own.
The respondent proposes a universal acceptance limit for the determination.
The respondent has read submission 003 and asks that this submission be considered with it.
The secretariat does not accept this submission. An appropriate limit depends on the compound, the presentation and the intended route, none of which the standard fixes.
The standard states performance and reports the figure as determined. Setting a universal limit would attach a pass or fail to materials whose acceptable ranges genuinely differ, which would be a stronger claim than the Institute can support. The submission remains published in full and the point is recorded in the limitations.
Quantitative claims are reproduced without the method that produced them
The respondent notes that CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations will be used as a checklist by people who have not read the rest of the series, and submits with that in view.
Several figures in the draft are quoted from sources that determined them by different methods. A figure obtained by one determination and a figure obtained by another are not comparable, and the draft places them in the same sentence without distinguishing them.
The respondent, an analytical chemist, proposes that every quantitative claim carry the method that produced it at the point of use rather than in the reference.
The secretariat accepts this submission. Placing two figures side by side is an implicit claim that they are the same kind of quantity, and in the cases identified they were not.
Every quantitative claim now carries the determination that produced it at the point of use, and figures obtained by non-comparable methods are no longer presented in the same row or sentence.
The scope does not say which materials the standard excludes
The respondent read the draft of CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations and has confined this submission to a single requirement.
The scope states what the standard applies to. The respondent states that in practice the difficult question is whether a borderline material is in scope, and that the draft leaves it to be inferred.
The respondent proposes an explicit exclusion list.
The secretariat accepts this submission. A scope stated only positively is a scope that will be stretched.
The scope now states both what the standard applies to and what it does not, with the excluded classes named and, where another standard covers them, cross-referenced.
A determination does not record the version of the standard it was made under
Having read the draft of CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations, the respondent puts one point to the secretariat.
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.
Nothing requires a laboratory to demonstrate ongoing performance
Having read the draft under consultation, which concerns CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations, the respondent submits as follows.
The respondent states that suitability criteria assessed within a run demonstrate that the run worked and not that the laboratory performs consistently over time.
The respondent proposes participation in a proficiency scheme as a condition of conformance.
Submission 002 raises an adjacent matter. The respondent regards the two as separable and addresses only this one.
The secretariat accepts this submission in part. A trend requirement on system suitability data is added. Proficiency scheme participation is not made a condition of conformance, for the same reason competence requirements are not.
The standard now requires that system suitability results be trended across runs and that a determination report whether the trend was within the laboratory's stated limits, which places the demonstration inside the document the Institute can read.
Nothing in the standard addresses transfer of the method between laboratories
The respondent read CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations in draft. The point applies to it and to the series generally.
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 document should state what a reader ought to do
The respondent has read CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations in draft and makes one submission.
The draft assesses evidence and stops. The respondent, a practising clinician, states that a reader arriving at the document with a decision to make is left to convert an assessment into an action without help, and proposes that each document close with a recommendation.
The respondent argues that other evidence bodies issue recommendations and that declining to do so transfers the difficult part of the work to the reader.
The secretariat does not accept this submission, and records that the point is a reasonable one rather than a misunderstanding.
The Institute assesses evidence and does not issue recommendations, because a recommendation embeds values and a resource context that the Institute does not hold and cannot state. That constitutional limit is published on the methodology page and is not varied by consultation. The submission remains published in full.
A field classified as critical is not one a reading turns on
This submission addresses the draft of CEI-MS-14, Certificate-of-analysis minimum data standard for synthetic peptide preparations from the standpoint of a reader who will rely on a conformance claim against it.
The respondent examines the fields classified as critical and states that two of them are administrative rather than interpretive, so that a certificate could be rendered uninterpretable by an omission that changes no reading.
The respondent proposes that a field be classified critical only where its absence changes what the figure means.
The secretariat accepts this submission in part. One field is reclassified as recommended on the test the respondent proposes. The second is retained as critical because its absence prevents the determination being attributed to a batch.
The classification test is now stated in the standard: a field is critical where its absence changes the meaning of a reported figure or prevents attribution to a batch. One field has been reclassified under that test and the reasoning recorded.
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.