ICH指导建议原则稳定性课件.ppt

ICH指导建议原则稳定性主要内容
ICH简介
ICH指导原则Q1A(R2)
ICH指导原则Q1B

ICH简介说明Q1A-Q1FStability稳定性Q1A(R2)StabilityTestingofNewDrugSubstancesandProductsStressTesting

强力破坏试验是通过建立降解途径，鉴定可能的降解产物，以确定分子的内在稳定性，并论证所使用的分析方法是否能反映产品的稳定性。
StressTesting

可以是单批原料药，包括温度（一般比加速试验温度高10℃）、湿度（75%或者更高）、氧化、光照。
SelectionofBatches批的选择

三批以上样品的数据
试产规模生产的批次，应与在最终规模生产时的合成路线和生产工艺相同。
用于稳定性研究的各批次原料药的总体质量应既能代表临床前研究的质量，又能代表临床研究以及规模生产时的质量。ContainerClosureSystem包装

与储存和运输的包装相同或相似Specification

稳定性研究应检验在储存期间容易变化的原料药的属性，并且可能影响原料药的质量，安全性和/或功效。检验应适当地涵盖物理，化学，生物和微生物方面。应采用经验证的分析方法。TestingFrequency
Forlongtermstudies,frequencyoftestingshouldbesufficienttoestablishthestabilityprofileofthedrugsubstance.Fordrugsubstanceswithaproposedre-testperiodofatleast12months,thefrequencyoftestingatthelongtermstorageconditionshouldnormallybeevery3monthsoverthefirstyear,every6monthsoverthesecondyear,andannuallythereafterthroughtheproposedre-testperiod.
Attheacceleratedstoragecondition,aminimumofthreetimepoints,includingtheinitialandfinaltimepoints(e.g.,0,3,and6months),froma6-monthstudyisrecommended.Whereanexpectation(basedondevelopmentexperience)existsthatresultsfromacceleratedstudiesarelikelytoapproachsignificantchangecriteria,increasedtestingshouldbeconductedeitherbyaddingsamplesatthefinaltimepointorbyincludingafourthtimepointinthestudydesign.

TestingFrequency

Whentestingattheintermediatestorageconditioniscalledforasaresultofsignificantchangeattheacceleratedstoragecondition,aminimumoffourtimepoints,includingtheinitialandfinaltimepoints(e.g.,0,6,9,12months),froma12-monthstudyisrecommended.

StorageConditions
1、Generalcase

*有显著变化时，增加中间条件

StorageConditions
2、Drugsubstancesintendedforstorageinarefrigerator

Ifsignificantchangeoccurswithinthefirst3months’testingattheacceleratedstoragecondition,adiscussionshouldbeprovidedtoaddresstheeffectofshorttermexcursionsoutsidethelabelstoragecondition,e.g.,duringshippingorhandling.可以进一步考察单批原料药在少于3个月内的稳定性，提高检样频率。

StorageConditions
3、Drugsubstancesintendedforstoragein