Impurity Qualification Thresholds: An IQ Survey on Emerging Industry Experience with Health Authority Feedback

An important objective during pharmaceutical development is minimizing impurities in drug substances and drug products to levels that minimize patient risk. Regulatory guidelines such as ICH Q3A and ICH Q3B provide impurity qualification thresholds for nonmutagenic impurities, but these guidelines are intended for commercial products and when applied during early clinical development this can lead to increased drug development time and resource use. This publication presents the results of a survey conducted by the International Consortium for Innovation and Quality in Pharmaceutical Development DruSafe member companies, which aimed to gather industry experiences using non-ICH Q3A/B impurity qualification thresholds. The survey revealed that many companies implement higher qualification thresholds during early development phases, with a shift toward strict ICH Q3A/B controls in later phases. Justifications for higher thresholds often include scientific rationale based on literature, Health Authority (HA) guidance, and toxicological principles. The findings suggest that global HAs are generally accepting of higher qualification thresholds during early development, provided there is an adequate justification. This publication discusses the implications of these findings for impurity management strategies and the potential for harmonizing regulatory approaches to impurity qualification.