Draft standard CEI-MS-09: Assessment of appearance, cake… — 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.
The additional determinations required would materially increase release testing cost
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.
The document is unreadable without specialist training
The respondent, a trustee of a patient organisation, 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.
The document should state what a reader ought to do
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.
Nothing requires the report to state who performed the determination
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.
A sortable table implies a comparison the underlying data do not support
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.
The limitations section states what the method cannot do but not what a reader will wrongly conclude
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 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.
Terms are used in senses that differ from established pharmacopoeial usage
The respondent, employed by a national competent authority and writing in a personal capacity, identifies three terms used in the draft in senses that differ from their established pharmacopoeial meanings.
The respondent proposes that established usage be followed or that the departure be stated explicitly at first use.
The secretariat accepts this submission. A term used in a private sense inside a document that will be read alongside compendial texts is a source of avoidable error.
The three terms now follow established pharmacopoeial usage, the glossary records the definition and its source, and where the Institute uses a term in a narrower sense the departure is stated at first use in the standard.
The scope does not say which materials the standard excludes
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 matrix interferes with the determination and no control is required
The respondent states that the matrices in scope can suppress or enhance the response, and that without an inhibition and enhancement control a result cannot be attributed to the analyte.
Data showing recovery outside acceptable limits in an uncontrolled matrix accompanied the submission.
The secretariat accepts this submission. A determination on an interfering matrix without a validated control establishes nothing, and the draft permitted one.
An inhibition and enhancement control is now required for every determination under this standard, with stated recovery limits, and a determination reported without it is recorded as not conformant rather than as a low result.
The search date is not on the face of the document
The draft carries a publication date and a review date but not the date on which the evidence was last searched. Those are three different dates and only the third tells a reader how current the assessment is. A document published in one quarter may rest on a search run two quarters earlier, and nothing on the page allows that gap to be measured.
The respondent proposes that the search date be printed adjacent to every certainty rating rather than in the methods section, on the ground that a reader who acts on a rating is unlikely to have read the methods section first.
The secretariat accepts this submission. The distinction between publication, review and search dates is real and the draft did not make it visible where it mattered.
The search date is now printed adjacent to every certainty rating and is carried in the document metadata, so that the interval between the search and the reading is visible without reference to the methods section.
The document should not describe uses outside the approved indication
The submission is made on behalf of a marketing-authorisation holder. It states that the draft describes uses of the compound that fall outside the approved indication, that such uses are not supported by the sponsor, and that describing them may be read as legitimising them.
The sponsor asks that the sections concerned be removed, or in the alternative that they carry a prominent statement that the sponsor does not support such use.
The secretariat does not accept this submission. The Institute records what is supplied and what is used, because a reader encountering a compound outside a regulated route is the reader most in need of an assessment of the evidence for it.
The sections remain. Every such section already states the regulatory status of the use described and states that the evidence for it is assessed separately from the evidence for the approved indication. The submission is published in full and identified as an industry submission.
Point estimates are given without an interval
Several estimates in the draft appear as single figures. The respondent states that a point estimate without an interval invites a precision the underlying data do not support, and that the effect is worst where the estimate is drawn from a small contributing set.
The respondent proposes that no point estimate appear anywhere in the document set without its interval, including in summary tables and in the abstract.
The secretariat accepts this submission in part. Intervals are added wherever the source reports one. The proposal is declined for figures the source published without an interval, because the Institute will not compute an interval a source did not report.
Every estimate now carries its interval where the source reported one, and where it did not, the estimate is annotated as reported without an interval rather than left to appear as a precise figure.
Nothing requires a laboratory to demonstrate ongoing performance
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.
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.