Grimm W
Analytical Sciences Department, Boehringer Ingelheim Pharma Deutschland, Biberach, Germany.
Drug Dev Ind Pharm. 1998 Apr;24(4):313-25. doi: 10.3109/03639049809085626.
The International Conference on Harmonization (ICH) Tripartite Guideline "Stability Testing of New Drug Substances and Products" sets out the stability testing requirements for a registration application within the three areas of the European Union, Japan, and the United States. These areas are assigned to climatic zone II with the storage condition of 25 degrees C/60% RH. This paper describes the adjustments that are necessary to extend the guideline to countries of climatic zones III and IV. At first storage conditions were derived with 30 degrees C/35% RH for climatic zone III and 30 degrees C/70% RH for climatic zone IV. Both conditions contain a margin of safety compared to calculated and measured data in warehouses. Furthermore, they cover the extreme temperatures above 30 and 40 degrees C which may arise in these climatic zones. Six months at 40 degrees C/75% RH was fixed as storage condition for accelerated testing to assess organoleptic and physicochemical test criteria and to make predictions for chemical stability. The predictive factor is 3.3 for 30 degrees C (6 months at 40 degrees C corresponds to 20 months at 30 degrees C). Extreme temperatures which may arise during shipment are covered by the results of stress investigations (e.g., 3 months at 50 degrees C). The next adjustment is necessary for the selection of the packaging containers. They must reflect the requirements for solid, semisolid, and liquid dosage forms caused by the two storage conditions. In the evaluation the temperature difference of 10 degrees C (40-30 degrees C) instead of 15 degrees C has to be considered, which limits the preliminary shelf lives in critical cases to 18 months instead of 24 months. Finally, statement/labeling must reflect the storage conditions. All of the other basic principles for the drug substances and drug products, such as selection and number of batches, test criteria, test procedures, specifications, testing frequency, and storage period can be applied without any change.
国际协调会议（ICH）三方指南《新药原料和产品的稳定性试验》规定了在欧盟、日本和美国三个地区进行注册申请的稳定性试验要求。这些地区被指定为气候区II，储存条件为25℃/60%相对湿度。本文描述了将该指南扩展到气候区III和IV国家所需的调整。首先，得出气候区III的储存条件为30℃/35%相对湿度，气候区IV为30℃/70%相对湿度。与仓库中的计算和测量数据相比，这两种条件都包含安全裕度。此外，它们涵盖了这些气候区可能出现的高于30℃和40℃的极端温度。40℃/75%相对湿度下6个月被确定为加速试验的储存条件，以评估感官和物理化学试验标准并预测化学稳定性。30℃时的预测因子为3.3（40℃下6个月相当于30℃下20个月）。运输过程中可能出现的极端温度由强化试验结果涵盖（例如，50℃下3个月）。下一个调整是关于包装容器的选择。它们必须反映两种储存条件对固体、半固体和液体剂型的要求。在评估中，必须考虑10℃（40 - 30℃）的温差，而不是15℃，这在关键情况下将初步货架期限制为18个月而不是24个月。最后，说明书/标签必须反映储存条件。原料药和药品的所有其他基本原则，如批次的选择和数量、试验标准、试验程序、规格、试验频率和储存期，都可以不作任何更改地应用。
