化学药物稳定性研究技术指导原则.doc

【 H 】 G P H 6 - 1 指导原则编号： 化学药物稳定性研究 技术指导原则 二○○四年十一月 目 录 一、概述··················································1 二、稳定性研究设计的要点··································1 （一）样品的批次和规模·······························1 （二）包装及放置条件·································2 （三）考察时间点·····································2 （四）考察项目·······································2 （五）分析方法·······································3 三、稳定性研究的试验方法·································3 （一）影响因素试验···································3 1.1高温试验······································4 1.2高湿试验······································4 1.3光照试验······································4 （二）加速试验········································5 （三）长期试验········································6 （四）药品上市后的稳定性研究··························6 四、稳定性研究的结果·····································6 （一）贮存条件的确定·································7 （二）包装材料/容器的确定····························7 （三）有效期的确定···································7 五、名词解释············································ 8 六、参考文献··············································8 七、著者·················································9 八、附录·················································9 （一）国际气候带·····································9 （二）低温和冻融试验··································10 （三）稳定性研究报告的一般内容························10 化学药物稳定性研究技术指导原则起草说明···············12 一、概述 药品的稳定性是指原料药及制剂保持其物理、化学、生物学和微生物学性质的能力。稳定性研究目的是考察原料药或制剂的性质在温度、湿度、光线等条件的影响下随时间变化的规律，为药品的生产、包装、贮存、运输条件和有效期的确定提供科学依据，以保障临床用药安全有效。 稳定性研究是药品质量控制研究的主要内容之一，与药品质量研究和质量标准的建立紧密相关。稳定性研究具有阶段性特点，贯穿药品研究与开发的全过程，一般始于药品的临床前研究，在药品临床研究期间和上市后还应继续进行稳定性研究。 本文为一般性原则，具体的试验设计和评价应遵循具体问题具体分析的原则。 二、稳定性研究设计的要点 稳定性研究的设计应根据不同的研究目的，结合原料药的理化性质、剂型的特点和具体的处方及工艺条件进行。 （一）样品的批次和规模 一般地，影响因素试验采用一批样品进行，加速试验和长期试验采用三批样品进行。 稳定性研究应采用一定规模生产的样品，以能够代表规模生产条件下的产品质量。原料药的合成工艺路线、方法、步骤应与生产规模一致；药物制剂的处方、制备工艺也应与生产规模一致。 稳定性研究中，原料药的批量应达到中试规模的要求。口服固体制剂如片剂、胶囊应为10000个制剂单位左右。大体积包装的制剂（如静脉输液等）的批量至少应为稳定性试验所需总量的10倍。特殊品种、特殊剂型所需数量，视具体情况而定。 （二）包装及放置条件 稳定性试验要求在一定的温度、湿度、光照条件下进行，这些放置条件的设置应充分考虑到药品在贮存、运