Degradation impurities

[snisyriou]

Hello!

I would like to ask, can a degradation impurity be unspecified? In a monograph can an unspecified (but listed) impurity be degradation impurity?

Thank you in advance

[JoNeu]

Yes, a degradation impurity can be unspecified. The advantage of a specified impurity is a higher level allowed in the drug substance or product. Or much lower in the case of mutagenic ones. However, this needs to be justified (toxicological concerns). Obviously, the identification of the impurity to be specified always is required.
Most of the impurities monographed are intermediates of the synthesis and are related to a specific synthesis route. Sometimes degradants are monographed. All impurities monographed can be considered as known.
Also check ICH guideline Q3A/B and Q6A: https://ich.org/page/quality-guidelines