1/ 13文件编号：XX-XX-1902产品亚硝胺杂质残留风险分析报告评估报告审批表部 门姓 名职 能签 名日 期QA起 草生产管理部审 核QC审 核108 车间审 核QA审 核QA 经理批 准1 评估依据：•按照《质量风险管理标准管理程序》的要求对产品中亚硝胺杂质残留进 行风险评2/ 13文件编号：XX-XX-1902估，确保产品中亚硝胺杂质残留符合 EMA 的要求。•ICH Q9a•ICH M72评估目的根 据 EMA 发 布 的 《 Informationon nitrosamines for marketing authorisation holders 》 以 及EDQM 发布的《Announcement to all CEP holders for synthesised APIs regarding presence of nitrosamines》的要求，对产品生产过程进行风险评 估，确定产品中是否有亚硝胺杂质残留。3风险评估3.1根据《Information on nitrosamines for marketing authorisation holders》中描 述的亚硝胺的来源：① Nitrosamine impurities can form during API processing under certain processing conditions and in the presence of some types of raw materials, starting materials, and intermediates. They may not be fully purged in subsequent steps of the API manufacturing process.在某些加工条件下、在某些类型的原料、起始原料和中间体的存在下， API 生产过程中可能形成亚硝胺杂质。 在 API 生产过程的后续步骤中可 能无法完全清除它们。② The use of sodium nitrite (NaNO2), or other nitrites, in the presence of secondary or tertiary amines is a potential cause of nitrosamine formation.在仲胺或叔胺的存在下使用亚硝酸钠(NaNO2)或其他亚硝酸盐是亚硝 胺形成的潜在原因。Secondary amines can be present in reagents and solvents as impurities or degradants. They may also be part of reagents, solvents, APIs, their degradants, and precursor structures. For example, amide solvents can degrade to secondary amines which are known sources of nitrosamines (such as N,N-dimethylformamide [DMF], N-methylpyrrolidone [NMP], or N,N-dimethylacetamide [DMA]).仲胺可以作为杂质或降解物存在于试剂和溶剂中。 它们也可能是试剂， 溶剂，API，其3/ 13文件编号...
