Draft standard CEI-MS-08: Related-substances profiling and… — submissions
The 9 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
9 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 prevents a chromatogram being reprocessed until it passes
This submission addresses the draft of CEI-MS-08, Related-substances profiling and the detection of isobaric impurities from the standpoint of a reader who will use a figure produced under it without having read it.
Integration parameters can be adjusted after acquisition, and nothing in the draft requires the sequence of processing to be recorded. A result presented as a single determination may be the last of several.
The respondent proposes that the standard require an audit trail of processing, retained with the primary data.
The secretariat accepts the principle and adopts a narrower requirement.
The standard now requires the processing method and its version to be recorded with every result and the primary data to be retained. A full audit trail is recommended and not required, since it depends on software many laboratories in scope do not run.
The standard assumes a reference standard of known assigned content
This is a submission on the draft of CEI-MS-08, Related-substances profiling and the detection of isobaric impurities, from the standpoint of a laboratory that would have to demonstrate conformance with it.
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 should be read alongside submission 001, which arises on the same draft.
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.
Acceptance criteria are expressed in terms specific to one instrument family
The respondent notes that CEI-MS-08, Related-substances profiling and the detection of isobaric impurities will be cited by suppliers as a warrant for a purity figure, and submits with that in view.
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.
Terms are used in senses that differ from established pharmacopoeial usage
Having read the draft of CEI-MS-08, Related-substances profiling and the detection of isobaric impurities, the respondent puts one point to the secretariat.
The respondent 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.
A field classified as critical is not one a reading turns on
The respondent read the draft of CEI-MS-08, Related-substances profiling and the detection of isobaric impurities and has confined this submission to a single requirement.
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 determination does not record the version of the standard it was made under
The respondent submits on the draft of CEI-MS-08, Related-substances profiling and the detection of isobaric impurities. A chromatographic purity determination is the figure most often quoted from a certificate and the one whose meaning depends most completely on the method behind it.
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 respondent notes that submission 005 has already been made and confines this submission to a matter not covered by it.
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 matrix interferes with the determination and no control is required
The respondent has read CEI-MS-08, Related-substances profiling and the detection of isobaric impurities in draft and makes one submission.
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 respondent has read submission 003 and puts a further matter to the secretariat.
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.
Nothing requires a laboratory to demonstrate ongoing performance
This submission concerns the draft standard CEI-MS-08, Related-substances profiling and the detection of isobaric impurities. The respondent runs reversed-phase separations of peptides daily and the observation arises from that work.
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 document is unreadable without specialist training
The draft of CEI-MS-08, Related-substances profiling and the detection of isobaric impurities was read against the instrumentation in general use in a hospital laboratory rather than against a research configuration.
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.
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.