Analytical Test Method Validation - General Guidence

pre-determined in order to properly select the validation experiment parameters before the test
method is developed and the validation exercise is begun.
To begin the validation exercise, individual sites can determine from Appendix 1 and 2 what
analytical elements should be evaluated for the particular test and sample of interest.
In the case that a limited set of elements are included in the validation, it is recommended that the
Method Validation Summary or protocol should address the reasons for limiting the validation to
the chosen elements.
Validation of the test procedures should take into account the reactivity of the sample. If the
sample can change over time, the validating scientist should attempt to find a means to quench
the reaction before analysis. While this is normally a method development activity, this
consideration should be evaluated by the site if method validation should occur at the sites. Once
execution of the method validation has begun, deviations and experimental failures should be
documented in the method validation report.
In some instances a set of experiments may be able to satisfy several validation parameters i.e.
robustness, intermediate precision and repeatability could be combined and studied together
instead of as isolated effects.
· For example, compendial physical tests such as LOD/ROI/pH where the analyst a
sample amount are primary contributors to variation and the method is well
defined in general chapters are ideal for this situation.
· An experiment could be constructed such that variations in sample size, analyst
and equipment could all be studied at once.
Documentation
It is recommended that sites have local site procedures for performing test method validation. For
methods in the scope of this guideline, sites may choose to prepare a protocol and obtain approval
prior to commencing validation. Alternatively an SOP containing pre-approved templates or
acceptance criteria guidelines could be used Because these test methods are generally lower risk
than those used to test final APIs, more flexibility in documentation of validation information
(e.g. use of an SOP versus a protocol) is considered acceptable.
Suggested criteria are included in this guideline on this topic; however criteria should be
directly linked to the method􀂶s intended use.
Method Validation Summary Report:
It is recommended to analyse the experimental results and prepare a Method Validation Summary
of the findings.
These method validation summaries may include but are not limited to:
􀂇 The performance results against criteria listed within this guideline, site SOP, or separate
pre- approved protocol.
􀂇 For higher risk methods, at least two reviewer signatures are recommended to be obtained
for the Method Validation Summary to be approved.