(完整版)灭菌无菌工艺验证指导原则.doc

PAGE\*MERGEFORMAT22灭菌/无菌工艺验证指导原则（第二稿）目录TOC\o"1-3"\h\z\uHYPERLINK\l"_Toc363042670"1概述PAGEREF_Toc363042670\h2HYPERLINK\l"_Toc363042671"2制剂湿热灭菌工艺PAGEREF_Toc363042671\h3HYPERLINK\l"_Toc363042672"2.1湿热灭菌工艺的研究PAGEREF_Toc363042672\h3HYPERLINK\l"_Toc363042673"2.1.1湿热灭菌工艺的确定依据PAGEREF_Toc363042673\h3HYPERLINK\l"_Toc363042674"2.1.2过度杀灭法的工艺研究PAGEREF_Toc363042674\h3HYPERLINK\l"_Toc363042675"2.1.3残存概率法的工艺研究PAGEREF_Toc363042675\h3HYPERLINK\l"_Toc363042676"2.2湿热灭菌工艺的验证PAGEREF_Toc363042676\h3HYPERLINK\l"_Toc363042677"2.2.1物理确认PAGEREF_Toc363042677\h3HYPERLINK\l"_Toc363042678"2.2.2生物学确认PAGEREF_Toc363042678\h3HYPERLINK\l"_Toc363042679"3制剂无菌生产工艺PAGEREF_Toc363042679\h3HYPERLINK\l"_Toc363042680"3.1无菌生产工艺的研究PAGEREF_Toc363042680\h3HYPERLINK\l"_Toc363042681"3.1.1无菌分装生产工艺的研究PAGEREF_Toc363042681\h3HYPERLINK\l"_Toc363042682"3.1.2过滤除菌生产工艺的研究PAGEREF_Toc363042682\h3HYPERLINK\l"_Toc363042683"3.2无菌生产工艺的验证PAGEREF_Toc363042683\h3HYPERLINK\l"_Toc363042684"3.2.1培养基模拟灌装试验PAGEREF_Toc363042684\h3HYPERLINK\l"_Toc363042685"3.2.2除菌过滤系统的验证PAGEREF_Toc363042685\h3HYPERLINK\l"_Toc363042686"4原料药无菌生产工艺PAGEREF_Toc363042686\h3HYPERLINK\l"_Toc363042687"4.1无菌原料药生产工艺特点PAGEREF_Toc363042687\h3HYPERLINK\l"_Toc363042688"4.1.1溶媒结晶工艺PAGEREF_Toc363042688\h3HYPERLINK\l"_Toc363042689"4.1.2冷冻干燥工艺PAGEREF_Toc363042689\h3HYPERLINK\l"_Toc363042690"4.2无菌原料药工艺验证PAGEREF_Toc363042690\h3HYPERLINK\l"_Toc363042691"4.2.1验证批量PAGEREF_Toc363042691\h3HYPERLINK\l"_Toc363042692"4.2.2最差条件PAGEREF_Toc363042692\h31概述无菌药品是指法定药品标准中列有无菌检查项目的制剂和原料药，一般包括注射剂、无菌原料药及滴眼剂等。从严格意义上讲，无菌药品应完全不含有任何活的微生物，但由于目前检验手段的局限性，绝对无菌的概念不能适用于对整批产品的无菌性评价，因此目前所使用的“无菌”