Draft standard CEI-MS-10: Identification and quantification… — submissions
The 16 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
16 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.
The standard would be applied more consistently with a worked example
The respondent submits on CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts. The point would apply equally to any document in the series.
The respondent states that the requirement most often misapplied in practice is the one the draft states most briefly, and that a worked calculation would settle it.
The respondent proposes a worked example showing the same data treated correctly and incorrectly, with both results stated.
The secretariat accepts this submission. An example showing only the correct treatment does not show the reader what they are doing wrong.
A worked example is added showing the same primary data treated two ways, with both resulting figures stated and the difference between them quantified, so that the consequence of the misapplication is visible rather than described.
The standard does not state that a determination on one unit says nothing about the batch
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 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 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.
Quantitative claims are reproduced without the method that produced them
The respondent’s comment on the draft of CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts arises from applying it to hygroscopic material in ordinary laboratory conditions.
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 respondent has read submission 001 above and makes this submission independently of it.
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.
A conformance claim is not defined and will be made loosely
Having read the draft under consultation, which concerns CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts, the respondent submits as follows.
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.
Submission 001 raises an adjacent matter. The respondent regards the two as separable and addresses only this one.
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.
A system suitability criterion is unachievable on instrumentation in general use
The respondent read the draft of CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts and has confined this submission to a single requirement.
The respondent, employed by a contract analytical laboratory, states that one of the suitability criteria in the draft can be met only on current-generation instrumentation, and that laboratories operating validated older systems would be unable to report a conformant determination.
Data from three instruments of different generations, showing the criterion met on one and missed on two, accompanied the submission.
The secretariat accepts this submission in part. The criterion is relaxed to the level the supplied data support for the general case, and retained at the stricter level for the specific discrimination that motivated it.
The suitability criterion is now stated at two levels, a general level achievable on instrumentation in common use and a stricter level required only where the standard is applied to the discrimination named in the scope, with the reason for the difference stated.
The scope does not say which materials the standard excludes
Having read the draft of CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts, the respondent puts one point to the secretariat.
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.
The document should state what a reader ought to do
The respondent has read CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts in draft and makes a single 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.
The standard assumes a reference standard of known assigned content
This is a submission on the draft of CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts, from a respondent working in peptide chemistry.
The respondent states that for many compounds in scope no reference standard with an assigned content exists, and that the standard as drafted has nothing to say to a laboratory in that position.
The respondent proposes that the standard state what can be determined without one and how such a determination should be labelled.
This submission is made by a respondent with a different professional interest in the outcome from the one behind submission 007.
The secretariat accepts this submission. A standard applicable only where a reference standard exists is silent in the cases most in need of it.
The standard now states which determinations remain available without a reference standard of assigned content, requires that such determinations be labelled as relative rather than absolute, and requires the assumption used in place of an assigned content to be stated.
Nothing states how long a prepared standard solution remains usable
The respondent read CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts in draft. The point applies to it and to the series generally.
The procedure requires a reference solution and does not say for how long it may be used. Peptide solutions at working concentration lose material to surfaces and to hydrolysis, and a solution used for a week will bias every result obtained against it in the same direction.
The respondent proposes that the standard require solution stability to be demonstrated over the period of use, or that a maximum period be stated.
The respondent has read submission 003 with interest and adds one observation the secretariat may find useful.
The secretariat accepts this submission. A systematic bias applied uniformly to a sequence is the hardest kind to notice.
The procedure now requires solution stability to be demonstrated over the period of intended use, and the demonstration to be recorded with the result.
The standard does not say what to do with a result outside the expected range
This is a submission on CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts.
The respondent states that the draft describes how to obtain a result and stops, and that the handling of an unexpected result is where the integrity of a determination is decided.
The respondent proposes that repetition be permitted only under stated conditions and that every determination performed be reported, including those superseded.
The secretariat accepts this submission. A standard silent on repetition permits the selective reporting it exists to prevent.
The standard now requires that every determination performed on a sample be reported, that a repeat be permitted only where an assignable cause is documented, and that the assignable cause be stated on the face of the report.
Nothing requires a laboratory to demonstrate ongoing performance
The respondent submits on the draft of CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts. 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.
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.
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.
The preparation solvent is not specified and changes what is measured
The draft of CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts was read from the standpoint of a laboratory that assigns content against a reference material.
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.
Absence of evidence is presented in a form a reader will take as negative evidence
The respondent has read CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts in draft and makes one submission.
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 010, 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 standard should require documented operator competence
This submission addresses the draft of CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts from the standpoint of a laboratory that performs the determination routinely.
The respondent states that the determination described requires judgement, particularly at the integration step, and that a competence requirement would improve consistency more than any change to the criteria.
The respondent proposes that conformance be conditional on documented operator training.
The secretariat does not accept this submission. Operator competence is a quality-system matter governed by accreditation requirements the Institute does not administer and cannot verify.
The standard states performance and remains silent on competence. Where judgement affects the result, as at the integration step, the standard requires the judgement to be recorded rather than the operator to be qualified, which is the part the Institute can check from a report. The submission remains published in full.
A single method cannot support the conclusion the standard permits
This submission concerns the draft standard CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts. 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 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.
A sortable table implies a comparison the underlying data do not support
This submission concerns CEI-MS-10, Identification and quantification of counter-ions in synthetic peptide salts and a convention used across the Institute’s output.
The draft presents a sortable table whose columns are drawn from sources of differing quality. The respondent states that sorting on such a column produces an ordering that looks like a ranking and is not one.
The respondent proposes that sorting be disabled on any column whose values are not commensurable.
The secretariat notes this submission and records that the point is correct in principle.
No amendment arises here because every sortable table in the document set already carries a standing statement above it that the ordering is not a ranking and that the values in each column are commensurable only where the column header says so. The proposal to disable sorting was considered and not adopted, because a reader who cannot sort a table generally sorts it elsewhere and without the statement.
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.