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.
Declared interests should appear on the document rather than on a separate page
The respondent read the draft of CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour and has confined this submission to a single requirement.
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 limitations section states what the method cannot do but not what a reader will wrongly conclude
The draft of CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour was read from the standpoint of a laboratory reconstituting material for analysis.
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.
A single method cannot support the conclusion the standard permits
The respondent has read CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour in draft and makes a single submission.
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 respondent has read submission 001 with interest and adds one observation the secretariat may find useful.
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 standard should state a pass limit
The respondent submits on the draft of CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour. A physical-quality attribute is informative and routinely left unreported, and a standard that makes one routine is worth having.
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.
This submission should be read alongside submission 001, which arises on the same draft.
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.
A field classified as critical is not one a reading turns on
Having read the draft of CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour, the respondent puts one point to the secretariat.
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 respondent has read submission 001 and puts a further matter to the secretariat.
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.
The standard specifies how to test a unit and not which units to test
This submission concerns the draft standard CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour. The respondent works in pharmaceutics and the observation concerns what an inspection actually detects.
A determination made on a unit chosen by the party being assessed supports a claim about that unit. The draft is precise about the procedure and silent about selection, which is where the inference from unit to batch either holds or fails.
The respondent proposes that the standard state a minimum sampling plan, or, where that is not practicable, require the selection method to be reported with the result.
The respondent has read submission 002 and asks that this submission be considered with it.
The secretariat accepts the reporting requirement. A minimum sampling plan is a matter for the party releasing the material.
The selection method is now a required field on every report made under this standard, and the limitations section states that a determination on a selected unit supports no inference about the batch.
Nothing addresses the container the material was held in
The respondent’s comment on the draft of CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour arises from performing examinations of this kind in a pharmacy setting.
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.
A determination does not record the version of the standard it was made under
The respondent submits on CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour.
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 draft prescribes a procedure where it should state performance
This submission concerns CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour and makes one point.
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.
A superseded version should remain reachable from the version that replaced it
This submission addresses the draft of CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour from the standpoint of a reader who will act on a result produced under it.
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.
Submission 004 raises an adjacent matter. The respondent regards the two as separable and addresses only this one.
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.
The matrix interferes with the determination and no control is required
The respondent notes that CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour will be applied to lyophilised material whose appearance changes on storage, and submits with that in view.
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.
This submission should be read alongside submission 002, which arises on the same draft.
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.
A system suitability criterion is unachievable on instrumentation in general use
This is a submission on the draft of CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour, made by a respondent who applies comparable procedures daily.
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 document should state what a reader ought to do
The respondent has read CEI-MS-09, Assessment of appearance, cake integrity and reconstitution behaviour 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.
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.