Draft standard: freeze–thaw and in-use stability assessment… — submissions
The 15 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
15 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 requires the report to state who performed the determination
The respondent’s comment on the draft of CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions arises from applying it to compounds that are unusually sensitive.
The respondent states that certificates in circulation frequently reproduce results generated by a third party without identifying it, and that a reader cannot tell whether the releasing party performed the work.
The respondent proposes that the performing laboratory be a required field.
The secretariat accepts this submission. Attribution of a determination is a precondition of assessing it.
The report now requires the identity of the laboratory that performed the determination, its accreditation status where claimed, and a statement of whether the releasing party is the performing party, with the fields classified as critical.
Nothing requires a laboratory to demonstrate ongoing performance
This is a submission on the draft of CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions, from a laboratory that stores reconstituted material between determinations.
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.
Results are reported without an estimate of measurement uncertainty
This is a submission on CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions.
The respondent, an analytical chemist, states that a figure reported to one decimal place implies an uncertainty the standard nowhere estimates, and that two determinations differing within the uncertainty will be read as a difference.
The respondent proposes that an uncertainty budget be required for every determination.
The secretariat accepts this submission in part. A repeatability figure and a stated reporting precision are required. A full uncertainty budget is not, because the standard is written to be usable by laboratories that do not maintain one and the requirement would exclude them without improving the reading.
Every determination now reports the repeatability observed in the run, the reporting precision, and a statement that two results differing by less than the stated repeatability are not distinguishable by this method.
A conformance claim is not defined and will be made loosely
The respondent has read CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions in draft and makes one 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.
This submission is made by a respondent with a different professional interest in the outcome from the one behind submission 002.
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.
Nothing addresses the container the material was held in
The draft of CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions was read by a respondent whose concern is the storage conditions a purchaser can actually achieve.
Adsorption to the container and oxidation in the headspace both change what is measured, and both depend on the container rather than on the material. The standard treats the vial as neutral.
The respondent proposes that container type and headspace atmosphere be reported where they are known.
The secretariat accepts the reporting requirement where the information is held and declines to require it where it is not.
Container type and headspace atmosphere are now reported where known, and recorded as not held where they are not, rather than omitted.
The document is unreadable without specialist training
Having read the draft of CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions, the respondent puts one point to the secretariat.
The respondent states that the draft is written for a reader who already understands certainty grading, and that the people most affected by the subject matter will not reach the assessment at all.
The respondent proposes a plain-language summary at the head of every document, written to the same standard of accuracy as the document itself and not as a promotional abstract.
The secretariat accepts this submission in part. A plain-language summary is added. The proposal that it replace the technical abstract is declined, because the abstract is the part of the document other assessors read and cite.
Every document now opens with a plain-language summary of not more than 150 words, placed above the technical abstract and carrying the same certainty language, so that the two cannot diverge.
A system suitability criterion is unachievable on instrumentation in general use
This submission concerns CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions and makes one point.
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 respondent has read submission 005 above and makes this submission independently of it.
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
The respondent submits on the draft of CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions. A stability statement is a claim about the future and needs a stated basis.
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.
Submission 005 raises an adjacent matter. The respondent regards the two as separable and addresses only this one.
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.
Acceptance criteria are expressed in terms specific to one instrument family
The respondent has read CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions in draft and makes a single submission.
The respondent states that two criteria are expressed in units reported by one manufacturer's software and not by others, which makes conformance a function of the instrument rather than of the determination.
The respondent proposes that criteria be expressed in instrument-independent quantities.
The secretariat accepts this submission in part. Both criteria are restated in instrument-independent terms. The conversion from the manufacturer-specific quantity is given rather than removed, because laboratories will continue to read it from their software.
The acceptance criteria are now expressed in instrument-independent quantities, with the conversion from the common manufacturer-specific reporting units given in a note so that a laboratory can check conformance without recalculating by hand.
The reporting threshold is not tied to a demonstrated limit of quantitation
This submission concerns the draft standard CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions. The respondent’s interest is in in-use periods and in what they rest on.
The draft sets a reporting threshold as a fixed percentage. The respondent states that whether a laboratory can quantify at that threshold depends on the signal-to-noise achieved, and that the threshold should be conditional on demonstrating it.
The respondent proposes that a determination be reportable only where the signal-to-noise at the threshold is demonstrated in the run.
The respondent notes that submission 002 has already been made and confines this submission to a matter not covered by it.
The secretariat accepts this submission. A threshold no one has demonstrated is a convention rather than a limit.
The reporting threshold is now conditional on demonstrating the required signal-to-noise at that threshold within the run, and a determination that cannot demonstrate it reports the achievable threshold instead of the nominal one.
Declared interests should appear on the document rather than on a separate page
This submission concerns CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions and a convention used across the Institute’s output.
The draft links to a central conflicts register. The respondent argues that a reader assessing whether to rely on a particular document should not have to leave it to find out who assessed it and what they declared.
The respondent proposes that the interests of every named contributor to a document be printed on that document.
The secretariat notes this submission and records that the draft already provides for it, which the respondent could reasonably have missed because the provision sits in an appendix.
Every document carries the declared interests of its named contributors in its front matter, and the central register exists so that a reader can see a person across all documents rather than one at a time. No amendment arises; the provision has been moved from the appendix into the body of the methodology document so that it is findable.
The draft prescribes a procedure where it should state performance
The respondent read the draft of CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions and has confined this submission to a single requirement.
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 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 limitations section states what the method cannot do but not what a reader will wrongly conclude
The respondent notes that CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions will be cited in support of a shelf life, and submits with that in view.
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.
This point is adjacent to the one made in submission 010 and the respondent puts it in a form the secretariat can act on.
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
Having read the draft under consultation, which concerns CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions, the respondent submits as follows.
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.
The respondent notes submission 001 above and does not repeat the ground it covers.
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.
The light source is not specified and results will not be comparable
This submission addresses the draft of CEI-MS-21, Freeze–thaw and in-use stability assessment of reconstituted peptide solutions from the standpoint of a laboratory that would run the study.
Photodegradation depends on the spectrum of the source as much as on the total exposure. Two laboratories exposing the same material to the same illuminance from different sources will obtain different degradation, and the standard as drafted permits both to claim conformance.
The respondent proposes that the source spectrum be specified, and that both the visible and the ultraviolet exposure be reported.
The secretariat accepts this submission. Exposure without a spectrum is not a specification.
The source spectrum is now specified and both exposures are required reporting fields.
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.