Читать книгу Mutagenic Impurities - Группа авторов - Страница 83
2.4.1.3 Question 1.3
Оглавление| Question | Answer |
|---|---|
| If an impurity generates negative predictions in two appropriate (Q)SAR systems and is present at a level less than or equal to 1 mg daily dose, is further genetic toxicity testing recommended? | No. If an impurity generates negative predictions in two appropriate (Q)SAR systems and is present at a level ≤1 mg/day, further genetic toxicity testing is not warranted. |
Interestingly, after Q&A 1.1 clearly explaining that the focus is on mutagenicity, the term used in this Q&A is “genetic toxicity testing” and not “mutagenic toxicity testing.” Does this mean that an impurity that is above the ICH Q3A/Q3B qualification threshold but has no (Q)SAR alerts and is found at less than 1 mg/day, there is no need for the Ames test or chromosomal aberrations? This is not clear, because the ICH Q3A and Q3B guidelines tell us that in order to qualify an impurity at a level above the qualification threshold you should test for mutagenicity (in the Ames test) and clastogenicity (in the chromosomal aberrations assay) in addition to general toxicity studies (one species, usually 14–90 days). The hope is that this topic will be further clarified in the final version of the Q&A document.
