Draft standard: determination of chromatographic purity by… — submissions
The 5 submissions received, published in full with declared interests and secretariat responses.
§2Submissions and responses
5 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
Having read the draft of CEI-MS-01, Determination of chromatographic purity of synthetic peptides by reverse-phase…, the respondent puts one point to the secretariat.
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.
The matrix interferes with the determination and no control is required
The draft of CEI-MS-01, Determination of chromatographic purity of synthetic peptides by reverse-phase… was read against the instrumentation in general use in a hospital laboratory rather than against a research configuration.
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 standard should require documented operator competence
The respondent notes that CEI-MS-01, Determination of chromatographic purity of synthetic peptides by reverse-phase… will be cited by suppliers as a warrant for a purity figure, and submits with that in view.
The respondent states that the determination described requires judgement, particularly at the integration step, and that a competence requirement would improve consistency more than any change to the criteria.
The respondent proposes that conformance be conditional on documented operator training.
The secretariat does not accept this submission. Operator competence is a quality-system matter governed by accreditation requirements the Institute does not administer and cannot verify.
The standard states performance and remains silent on competence. Where judgement affects the result, as at the integration step, the standard requires the judgement to be recorded rather than the operator to be qualified, which is the part the Institute can check from a report. The submission remains published in full.
The standard should state a pass limit
The respondent has read CEI-MS-01, Determination of chromatographic purity of synthetic peptides by reverse-phase… in draft and makes one submission.
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 respondent supports submission 002 so far as it goes and adds the matter set out here.
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.
Nothing addresses the container the material was held in
The respondent submits on the draft of CEI-MS-01, Determination of chromatographic purity of synthetic peptides by reverse-phase…. 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.
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.
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.