As published by EMA/CMDh/587072/2022
Report from the CMDh meeting held on 21-22 June 2022
In September 2021 the CMDh has published a letter addressed to MAHs of losartan-containing medicinal products to ask them to review if there is a risk of contamination of their product with an azido impurity (5-[4’ -[(5-(Azidomethyl)-2-butyl-4-chloro-1 H-imidazol-1-yl)methyl]-[1,1’-biphenyl]2-yl]-1H-tetrazole (CAS 727718-93-6) (‘losartan azide impurity’)).
This request was issued after it was confirmed that this impurity has tested positive in a bacterial mutagenicity (Ames) test and that therefore it should be ensured that the impurity is controlled at or below the Threshold of Toxicological Concern (TTC) as outlined in ICH M7 for known mutagens with unknown carcinogenic potential (class 2) via a suitable control strategy.
In November 2021 the CMDh communicated that uncertainties regarding the validity of the Ames test have been raised. It has now been confirmed by this new information that the losartan azide impurity is not an in vivo mutagen.
This means that losartan azide is classified as a class 5 impurity in accordance with ICH M7(R1) and can be controlled as a nonmutagenic impurity in accordance with ICH Q3A/B.
CMDH PRESS RELEASES
Azido impurity in losartan confirmed positive in bacterial mutagenicity test - action needed (informa.com)