欧盟药品贮运声明指南

欧盟药品贮运声明指南
1. BACKGROUND 背景
Suitable storage conditions, consistent with those defined in the SPC should be included in the package leaflet and on the product labelling, if appropriate, as stated in Directive 2001/83/EC. The storage conditions for medicinal products should be based on evaluation of the stability studies undertaken on the finished product. Details of the conditions recommended for these stability studies are included in the relevant CHMP/ICH Guidelines where storage conditions for real time studies were chosen as 25°C/60% RH supported by accelerated or, where applicable, intermediate conditions and based on the mean kinetic temperature of climatic zone I/II, the relevant zone for the EU. The mean kinetic temperature includes the annual variations, i.e. lower and higher temperatures during winter and summer seasons. Thus, storage at a continuous temperature of 25°C during real time stability studies covers the actual temperature exposure likely to be encountered under ambient conditions throughout Europe, including real time excursions from 25°C.
与其在SPC中定义相一致的适当的存贮条件，应包括在包装说明书里以及在药品标签上。

适当时，与指令2001/83/EC一致。

药品的存贮条件应基于对制剂所做的稳定性试验的评估上。

所建议的这些稳定性试验条件包括在相关的CHMP/ICH指南中，其中存贮条件实时研究被选择为25°C/60% RH，由加速或中间条件来支持，并且是基于气候带I/II和相关EU气候带的平均动态温度。

平均动力学温度包括年度变化，即冬季和夏季较低和较高的温度。

这样，在实时稳定性研究中持续存贮于25°C就会包括了实际可能遭遇的整个欧洲范围内室温下温度暴露情形，包括实时温度偏出25°C的情形。

2. OBJECTIVE 目的
The purpose of this guideline is to set out uniform statements on storage conditions for inclusion in the labelling of medicinal products and to define when they apply.
本指南的目的是设定药品标签中所要包括的存贮条件的统一声明，以及界定什么时候适用它们。

3. SCOPE 范围
This guideline is intended as an Annex to the stability guidelines and relates to marketing authorisations for all product categories.
本指南意在作为稳定性指南的附录，与所有药品类型上市许可相关。

4. CORE STORAGE STATEMENTS 核心存贮声明
The storage conditions must be possible for the user to follow and it is therefore necessary to restrict the statements to those achievable in practice. Results from stability studies, presented at the time of submission, should serve as guidance and there should be a direct linkage between the label statements and the demonstrated stability characteristics of the finished product. However, a storage statement cannot be used to compensate for insufficient stability data, e.g. omission of stability studies at accelerated or intermediate testing conditions. The use of terms such as ‘room temperature’ or ‘ambient conditions’ is unacceptable.
存贮条件必须是用户可以达到的，因此有必要将声明限制在实际可达到的情形中。

在申报时会呈报的从稳定性研究而来的结果应作为指导，在标签声明和所证明的制剂稳定特性之间应该有直接关联。

但是，存贮声明不能用于补偿不足的稳定性数据，例如，忽略稳定性研究中加速和中间试验条件。

使用术语如“室温”或“常温”是不能接受的。

Testing conditions R equired labelling A dditional labelling
where the product is stable
statement
statement*, where relevant 产品保持稳定的试验条件
所需的标签声明
额外标示声明（相关时） 25°C/60%RH (long term) 40°C/75%RH
(accelerated) or
30°C/65%RH (long
term) 40°C/75%RH
(accelerated)
None***
Do not refrigerate or freeze 25°C/60%RH (长期) 40°C/75%RH (加
速) 或 30°C/65%RH (长期)
40°C/75%RH (加速)
无
不要冷冻或冷藏
25°C/60%RH (long term) 30°C/60 or 65%RH (intermediate) or 30°C/65%RH (long
term)
Do not store above 30°C or Store below 30°C
Do not refrigerate or freeze
25°C/60%RH (长期) 30°C/60 or 65%RH (中间)
or 30°C/65%RH (长期)
不要超过 30°C 或者 低于30°C 存贮
不要冷冻或冷藏
25°C/60%RH (long term) Do not store above 25°C or Store below 25°C
Do not refrigerate or freeze
25°C/60%RH (长期) 不要超过25°C 或 低于25°C 存贮
不要冷冻或冷藏
5°C ±3°C (long term) Store in a refrigerator or Store
and transport
refrigerated ****
**
Do not freeze
5°C ±3°C (长期) 在冰箱存贮或
冷藏贮运 *** 不要冷冻
**
Below zero Store in a freezer or
Store and transport
frozen *****
**
低于零度在冷冻柜保存或
冷冻贮运*****
**
* Depending on the pharmaceutical form and the properties of the product, there may be a risk of deterioration due to physical changes if subjected to low temperatures. Low temperatures may also have an effect on the packaging in certain cases. An additional statement may be necessary to take account of this possibility.
根据剂型特性的不同，如果在低温下可能会由于物理特性的变化引起变质的风险。

低温可能也会对特定情形下的包装产生影响。

可能需要有附加声明来考虑这种可能性。

** The SPC and Package Leaflet (PL) should include a reference to the temperature range e.g. (2°C to 8°C)
SPC和说明书（PL）应包括对温度范围的引用即(2°C to 8°C)
*** The following SPC and PL statements are required: This medicinal product does not require any special storage conditions.
需要有以下SPC和PL声明：此药品不需要任何特殊存贮条件。

**** The stability data generated at 25°C/60%RH (acc) should be taken into account when deciding whether or not transport under refrigeration is necessary. The statement should only be used in exceptional cases.
当决定是否有必要在冷藏条件下运输时，要考虑在25°C/60%RH （加速）条件下产生的稳定性数据。

声明应仅在例外情形下使用。

*****The statement should only be used when critical.
声明应仅在关键情况下使用。

The exact wording of the statements given in the table above will be applied throughout the Community taking into consideration that because of national linguistic and cultural differences, two alternatives are presented for storage below 25°C and below 30°C, respectively, and it is the decision of the competent authority which of these should be used.
在整个欧盟应使用上表中原字句，同时考虑国家语言和文化差异。

有2种条件即低于25°C和低于30°C是可以相互替代的，要由国家药监局来决定应使用哪一个。

Any other statements are only acceptable if unavoidable and, in particular, where the core storage statements are documented to be inappropriate. The alternative proposal is to be supported by relevant data and must be realistically achievable in practice.
只有在不可避免的情况下才接受其它的声明，即核心存贮声明已有书面记录说是不适当的时候。

可替代建议应由相关数据支持，并且是实际操作中现实可达到的条件。

5. OTHER SPECIFIC STORAGE STATEMENTS 其它特殊存贮声明
In principle, medicinal products should be packaged in containers that ensure stability and protect the finished product from deterioration. A storage statement should not be used to compensate for inadequate or inferior packaging. Nevertheless, the following statements may be used to emphasise the need for precautions to the patient.
原则上，药品应包括在容器中，确保其稳定性，保护制剂不变质。

一个存贮声明不应被用于补充不充分或低劣的包装。

当然，以下声明可以用于强调引起患者注意。

Storage problem Additional labelling statements* depending on the packaging
存贮问题根据包装不同所需额外标签声明
1.
Sensitivity to moisture Keep the container*** tightly closed
对湿度敏感 将容器闭紧 2.
Sensitivity to moisture Store in the original package
对湿度敏感 存贮的原始包装中 3. Sensitivity to light** S tore in the original package
对光敏感 存贮的原始包装中 4.
Sensitivity to light** Keep container*** in the outer carton
对光敏感 将包装保存在外包盒内
* When such a standard statement is used, an explanation specifying whether the product is sensitive to light and/or moisture should be added.
当使用了这样的标准声明时，应增加解释说明药品是否对光和/或湿度敏感。

** Details of evaluation are included in the CPMP/ICH Guideline on photostability testing.
在CPMP/ICH 光稳定性测试指南中有评估详情。

*** The actual name of the container should be used, e.g. bottle, blister
要使用实际容器名称，例如，瓶、泡罩
Where a supplementary warning, e.g. “Store in the original package” is required, the SPC statement “This product does not require any special storage conditions” (see footnote to the table in 4.) should be revised to read “This medicinal product does not require any special temperature storage conditions” as necessary.
如果需要有补充警示，例如“存贮在原始包装中”，则在必要时，应将SPC 声明“本药品不需要任何特殊的存贮条件”（参见第4部分表中脚注）修订为“本药品不需要任何特殊的温度存贮条件”。

The exact wording of the above texts will be uniformly applied throughout the Community.
上述原字句在整个欧盟统一适用。

NOTE FOR GUIDANCE ON:
B. DECLARATION OF STORAGE CONDITIONS FOR ACTIVE
SUBSTANCES
B: 原料药贮运条件申明指南注解
The storage conditions for active substances should be based on evaluation of the stability studies undertaken on the active substance. The principles elaborated above in relation to standard storage declarations for finished medicinal products should also form the basis for storage declarations of active substances.
原料药的存贮条件应基于对原料药所做稳定性试验的评估。

上述针对制剂的标准存贮声明制订原则也是原料药存贮声明的基础。

For substances to be stored/transported refrigerated or frozen, the temperature range should be included in the labelling.
对于要在冷藏或冷冻条件下存贮/运输的原料药，应在标签中包括温度范围。