Validation requirements on establishment or revision of a standardized reference method

Validation requirements on establishment or revision of a standardized reference method

The technical stages of the establishment of a new standardized reference method or the revision of an existing standardized reference method have been described in standard ISO 17468.

Validation required after revision depends on the nature of the changes in the method.

Learn more about ISO 17468, major and minor changes and their impact.

ISO 17468:2016 ‘Microbiology of the food chain – Technical requirements and guidance on establishment or revision of a standardized reference method’ has been developed in order to set common rules for the validation of reference methods standardized in the field of food microbiology by ISO/TC 34/SC 9 and its corresponding structure at European level (CEN/TC 463 ‘Microbiology of the food chain’). It defines the technical stages of the establishment of a new standardized reference method or the revision of an existing standardized reference method in International Standards.

Five technical stages are followed for the validation of a method in its standardization process as a reference method, the last one consisting of an interlaboratory study (ILS). The performance characteristics of the method are calculated based on these ILS data. Performance characteristics are not detailed in ISO 17468 but cross-referenced to the appropriate clauses of ISO 16140-2:2016.

 

Major/minor changes in the revision of International Standards

Validation required for the revision of an existing International Standard, i.e. a standardized reference method, depends on the nature of the technical changes in the method, whether they are minor or major.

A major technical change is, for example, a modification in the method detection/quantification technology or a substantial technical modification of the procedure (e.g. nature of the enrichment broth or isolation agar, incubation time and/or temperature). It is expected to produce a different result. An example for a major technical change is shown in ISO 21528-1:2017, ISO 22964:2017 or ISO 10273:2017.

A minor technical change is, for example,  a technical change that is not expected to affect the result. An example for a minor technical change is shown in ISO 10272-1:2017 & ISO 10272-2:2017 for detection or enumeration of Campylobacter spp., where the confirmation tests on microaerobic growth at 25 °C and aerobic growth at 41,5 °C were replaced by aerobic growth at 25 °C.

When only editorial changes to the text of the method are made during the revision this is regarded as a minor technical change.

If the technical change in the method is evaluated as being major, a re-validation of the method is needed. When the re-validation of the method is conducted, the impact on the performance characteristics shall be evaluated to determine if the changes are to be regarded as major (performance characteristics have substantially changed) or minor (no impact on performance characteristics observed). In certain cases, a major technical change in the method can be considered to be minor, if the re-validation study shows that it has no significant effect on the performance characteristics or test results. An example for a major technical change considered as minor is shown in ISO 11290-1:2017 & ISO 11290-2:2017.

 

Impact of a major change

A major change with impact on performance characteristics of a standardized reference method will lead to a re-validation of proprietary methods according to ISO 16140-2 in comparison to the revised standardized reference method. It will also involve a verification of the revised standardized reference method by user laboratories according to ISO 16140-3:2021).

Upon revision of a standardized reference method a statement on the changes made (minor or major and with or without impact on performance characteristics) will be included in the introduction of the revised International Standard.

More information on (proprietary) method validation and method verification can be found here.

 

Current revision of ISO 17468

ISO/TC 34/SC 9/WG 3 ‘Method validation’ is currently revising ISO 17468 for different reasons, mainly:

  • to include details on the assessment of major and minor changes in a reference method and its impact on method validation and method verification;
  • to update cross-references to the ISO 16140 series for the definition of performance parameters;
  • to include in an annex an experimental design of studies to compare different options in the development of the new reference method or for its revision.