Draft standard CEI-MS-07: Sub-visible particulate matter in… — 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 standard does not state that a determination on one unit says nothing about the batch
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.
A determination does not record the version of the standard it was made under
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 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 standard does not say what to do with a result outside the expected range
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.
A system suitability criterion is unachievable on instrumentation in general use
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.
A single determination is permitted where duplicates would be inexpensive
The respondent states that the draft permits a result to be reported from one injection, and that the marginal cost of a duplicate is small relative to the value of detecting a preparation error.
The respondent proposes that duplicate determinations be mandatory.
The secretariat accepts this submission in part. Duplicate preparation and injection are required, and a criterion for agreement between them is stated. The proposal to require full duplicate sample preparation on separate days is declined as disproportionate.
The standard now requires duplicate preparation and injection with a stated maximum difference between the two, and requires that a difference exceeding it be investigated before any figure is reported.
The reporting threshold is not tied to a demonstrated limit of quantitation
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 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.
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 standard assumes a reference standard of known assigned content
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.
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.
The standard should state a pass limit
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 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.
The document set should be published in translation
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 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.
A field classified as critical is not one a reading turns on
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.
A conformance claim is not defined and will be made loosely
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.
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.