Читать книгу Mutagenic Impurities - Группа авторов - Страница 84
2.4.1.4 Question 1.4
Оглавление| Question | Answer |
|---|---|
| What are the expectations for evaluation of the genotoxic potential for an impurity where the amount of impurity exceeds 1 mg daily dose? | In cases where the amount of impurity is >1 mg daily dose for chronic administration, regardless of the impurity classification, a minimum screen of genotoxicity studies (point mutation and chromosomal aberration) can be considered. |
This Q&A clarifies the situation where even if the impurity is a Class 4 or Class 5, if it is present at above 1 mg/day, you are compelled to perform an Ames test and a chromosomal aberrations assay in order to complete the qualification. The question that arises here is: What is the rationale behind requiring the Ames test in such a situation? If the entire basis of classifying impurities in the ICH M7 guideline is based on (Q)SAR analysis, and an impurity can be classified as being nonmutagenic, then why does this classification not prevail also when the level exceeds 1 mg/day? This is not a logical recommendation and here again the hope is that this topic will be further clarified.
