Regulatory Thresholds and Qualification

Reporting, Identification and Qualification Thresholds International Council for Harmonisation guidelines Q3A and Q3B establish a tiered system of...

Reporting, Identification and Qualification Thresholds

International Council for Harmonisation guidelines Q3A and Q3B establish a tiered system of thresholds governing the regulatory handling of impurities in new drug substances and new drug products respectively. The reporting threshold defines the concentration above which an impurity must be reported in analytical results and specifications; the identification threshold defines the concentration above which the structural identity of an impurity must be established, typically through spectroscopic or mass spectrometric characterisation; and the qualification threshold defines the concentration above which the safety of the impurity must be demonstrated through toxicological data or documented biological safety justification. These thresholds are expressed as a function of the maximum daily dose of the drug product, reflecting the principle that impurity control should be proportionate to patient exposure.

Regulatory Perspective

The impurity thresholds and reporting expectations established in International Council for Harmonisation Q3A, Q3B, Q3C, Q3D, and M7 collectively define the regulatory expectations against which impurity specifications in drug substance and drug product dossiers are evaluated during marketing authorisation review.