Sign-off and Documentation

Method validation is carried out to provide objective evidence that a method is suitable for a given application. A formal assessment of the validation information against the measurement requirements specification and other important method performance parameters is therefore required. Although validation is described as a sequential process, in reality it can involve more than one iteration to optimize some performance parameters, e.g. if a performance parameter is outside the required limits, method improvement followed by revalidation is needed. 

Method validation provides information concerning the method s performance capabilities and limitations, when applied under routine circumstances and when it is within statistical control, and can be used to set the QC limits. The warning and action limits are commonly set at twice and three times the within-laboratory reproducibility, respectively. When the method is used on a regular basis, periodic measurement of QC samples and the plotting of these data on QC charts is required to ensure that the method is still within statistical control. The frequency of QC checks should not normally be set at less than 5% of the sample throughput. When the method is new, it may be set much higher. Quality control charts are discussed in Chapter 6. 

The validation is therefore not complete until there is a detailed description of the method and records of the validation study. A responsible person needs to sign that the method meets the requirements, i.e. it is fit for purpose . The documentation facilitates the consistent application of the method, within its scope and defined performance parameters. This, in turn, helps ensure that when the method is applied in different laboratories or at different times, the measurand is the same and that the measurement results are comparable. Documentation is also required for quality assurance, regulatory and contractual purposes. 

Changes to methods will occur due to changes in applications and technological developments and these changes need to be formally implemented and recorded, after appropriate validation. A periodic review (commonly every two years) and, where necessary, revision is considered to be good practice . 

A system of document control, including restricting unofficial copying, is required, in order to ensure that only authorized methods are used and that these are the latest revisions. This requires attention to details, such as revision number, who authorized the method, who has amended it, issue date, date of next revision, number of copies and who owns them, etc. A variety of documentation formats are available, but a standard format for method documentation is provided in ISO 78-2 1999 and a layout based on this Standard is provided in the Appendix to this chapter [18]. 

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