原料药及制剂的质量标准制定(2011年).pdfVIP

原料药及制剂的质量标准制定原料药及制剂的质量标准制定 2011 药典标准药典标准 • USPUSP • EP • JPJP • CP • BP • WHOWHO • 新药质量标准 ICHICH 指南指南 • Q6AQ6A SpecificationsSpecifications :: TestTest ProceduresProcedures andand Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances (including Decision Trees) • Q3A(R2) Impurities in New Drug Substances • Q3B(R2) Impurities in New Drug Products • Q3C(R4) Impurities: Guideline for Residual Solvents 非专利药质量标准非专利药质量标准 • 原料药和制剂原料药和制剂 – 比较老的药有药典标准 – 比较新的药不一定有药典标准比较新的药不一定有药典标准 • 药典标准的问题 – FDA不不一定完全接受药典的质量标准参数定完全接受药典的质量标准参数 – 比较老的药典标准不一定满足ICH要求 – 分析方法过于老化 原料药原料药 • DescriptionDescription:: – 定性描述 a qualitative statement about the statestate (e(e.gg. solidsolid, liquid)liquid) andand colorcolor ofof thethe newnew drug substance. – 晶体的问题晶体的问题，，CrystallineCrystalline solid?solid? – 例子: White to off-white powder 原料药原料药 • Identification – FTIR 红外是最常用的. – 单一色谱出峰时间依据不够 A single chromatographic retentionretention time,time, forfor example,example, isis notnot regardedregarded asas beingbeing specific. – 同时使用两种色谱可以接受 Use of two chromatoggrapphic pprocedures,, such as HPLC/UV diode array, HPLC/MS, or GC/MS is generally acceptable. – 盐需要具体测试 An identification test that is sppecific for the salt itself should suffice. – 手性分子测试 Optically active may also need specific identification testing or performance of a chiral assay. – 例子: FTIR and HPLC retention time. 原料药原料药 • Assayy: – 专一，可以测定稳定性的主要成分定量测试方法A specific, stability-indicating procedure should be included to determine the content. In many cases it is