ICH Q3B(R2) - Impurities in New Drug Products

What it says

Degradation products observed in new drug products during manufacture and storage must be identified above defined reporting, identification and qualification thresholds that scale with the maximum daily dose, with qualification requiring toxicological or clinical data supporting the safety of a degradation product at the level observed.

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

What it means in practice

• Threshold-based control means the same absolute quantity of a degradation product can require different levels of scrutiny depending on the product's maximum daily dose - lower-dose products carry proportionally stricter identification and qualification expectations.
• Qualification of a degradation product above the relevant threshold requires actual toxicological or clinical safety data specific to that impurity, not simply analytical characterisation of what it is.
• This guideline works directly with forced degradation study design under ICH Q2(R2) and Q1A(R2), since degradation products observed during those studies are exactly what this framework governs the control strategy for.

What inspectors look for

• Whether degradation products observed above the applicable threshold have been properly identified and, where required, qualified with genuine safety data.
• Whether reporting, identification and qualification thresholds applied are correctly calculated based on the product's actual maximum daily dose.
• Whether new or increasing degradation products observed during ongoing stability testing trigger reassessment against these thresholds, not just at initial registration.

Related regulations