从FDA缺陷信看致突变杂质的鉴别与分类

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近日，收到某项目的 FDA DMF 文件缺陷信，要求补充研究的内容大部分都是涉及致突变杂质的鉴别、分类、定性和控制。部分内容如 “We acknowledge that you discuss control strategy for the impurities which could be present in the drug substance in sections 3.2.S.2.3, 2.4, and 3.2. We also acknowledged that you have provided risk assessment of potential genotoxicity for the PMIs listed in the  section 3.2.S.3.2 . However, we were unable to locate a hazard assessment for most of the actual as well as potential impurities in your submission. A complete hazard assessment for actual and potential impurities is recommended in Section 6 of the ICH M7 Guidance: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk. Section 6 of the guidance describes the elements required for impurity hazard assessment and requires classification of each impurity according to Table 1. Classification of a ………………………………