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Section 6 of the guideline further states that (emphasis added): “To follow up on a relevant structural alert (Class 3 in table 1), either adequate control measures could be applied or a bacterial mutagenicity assay with the impurity alone can be conducted. An appropriately conducted negative bacterial mutagenicity assay (Note 2) would overrule any structure‐based concern, and no further genotoxicity assessments would be recommended (Note 1). These impurities should be considered non‐mutagenic (Class 5 in table 1).”

Question	Answer
In a case where an impurity is demonstrated to be negative in an Ames study but positive in a clastogenicity study (e.g. chromosomal aberration test), how would the impurity be classified per the ICH M7 classification system?	If an impurity tests negative in an Ames assay, it is considered a Class 5 impurity. Addressing positive results in a clastogenicity assay is out of scope of ICH M7.

As discussed above in Question 1.1, it is made explicitly clear that if an impurity is negative in the Ames test and even if it is positive in the chromosomal aberrations assay (clastogenic), this impurity is considered a Class 5 impurity.