ICH Q2(R2) - Validation of Analytical Procedures

What it says

Analytical procedures must be validated against parameters appropriate to their intended use, evaluated to an extent proportionate to the method's purpose, covering specificity, accuracy, precision, detection limit, quantitation limit, linearity, range and robustness.

Paraphrased for plain-language clarity. Always verify against the current published regulation text.

What it means in practice

• Not every parameter applies with equal weight to every method type - which parameters matter most depends on whether the method is used for identification, impurity testing or assay, and that scope decision must itself be documented.
• Specificity is established primarily through forced degradation studies, deliberately stressing the sample to confirm the method can distinguish the analyte from degradation products, not assumed from the absence of previously observed degradants.
• A method change, even one that appears minor such as a detection wavelength adjustment, requires a documented assessment of which validation parameters the change could plausibly affect.

What inspectors look for

• Whether forced degradation studies used to support a specificity claim reflect a genuine, appropriately targeted stress condition rather than being absent, insufficient, or excessive.
• Whether method changes are treated as requiring assessment, through full validation, partial validation or verification as appropriate, rather than assumed to be automatically covered by the original validation.
• Whether reference standard source, lot and purity traceability is documented, since every quantitative parameter depends on comparison against a reference standard of known identity.

Related regulations