Annex 19: Reference and retention samples

附录 19：对照样品和留样

2022 年 02 月 01 日 发布

原文件 1 历史版本（Version List）

发布日期 标题 状态
2022-02-01 Annex 19: Reference and retention samples 双语版 现行
2021-04-26 Annex 19: Reference and retention samples 非现行
2022/02/01 [pdf]
中译为审校版
目录
 1. SCOPE
 2. PRINCIPLE
 3. DURATION OF STORAGE
 4. SIZE OF REFERENCE AND RETENTION SAMPLES
 5. STORAGE CONDITIONS
 6. WRITTEN AGREEMENTS
 7. REFERENCE SAMPLES – GENERAL POINTS
 8. RETENTION SAMPLES – GENERAL POINTS
 9. REFERENCE AND RETENTION SAMPLES FOR PARALLEL IMPORTED / PARALLEL
DISTRIBUTED PRODUCTS
 10. REFERENCE AND RETENTION SAMPLES IN THE CASE OF CLOSEDOWN OF A
MANUFACTURER

1. SCOPE
1. 范围
1.1 This Annex to the Guide to Good Manufacturing Practice for Medicinal Products （"the GMP
Guide"） gives guidance on the taking and holding of reference samples of starting materials,
packaging materials or finished products and retention samples of finished products.
1.1 本《药品生产质量管理规范指南》（简称《GMP 指南》）附录对起始物料、包材或成品的参考
样和成品留样的采集和贮存提供了指导。
1.2 Specific requirements for investigational medicinal products are given in Annex 13 to the
Guide.
1.2 临床试验用药品的特殊要求详见 GMP 指南附录 13。
1.3 This annex also includes guidance on the taking of retention samples for parallel imported /
distributed medicinal products.
1.3 本附录也包括了关于平行进口/平行分销药品留样的指导。
2. PRINCIPLE
2. 原则

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2.1 Samples are retained to fulfil two purposes; firstly to provide a sample for analytical testing and
secondly to provide a specimen of the fully finished product. Samples may therefore fall into two
categories:
2.1 保留样品有两个目的：一是提供分析检验的样品；二是提供成品的样本。因此样品可以分为两类：
Reference sample: a sample of a batch of starting material, packaging material or finished product
which is stored for the purpose of being analyzed should the need arise during the shelf life of the
batch concerned. Where stability permits, reference samples from critical intermediate stages
（e.g. those requiring analytical testing and release） or intermediates that are transported
outside of the manufacturer's control should be kept.
参考样：指一批起始物料、包材或成品的样品，贮存起来待相关批次有效期内需要时供分析之用。
如稳定性允许，应保存关键生产阶段（例如，需进行分析检验与放行的阶段）的样品或运输到生产
企业控制外的中间体样品作为参考样。
Retention sample: a sample of a fully packaged unit from a batch of finished product. It is stored for
identification purposes. For example, presentation, packaging, labelling, patient information leaflet,
batch number, expiry date should the need arise during the shelf life of the batch concerned. There
may be exceptional circumstances where this requirement can be met without retention of
duplicate samples e.g. where small amounts of a batch are packaged for different markets or in the
production of very expensive medicinal products.
留样：从一批成品中抽取的完整包装单元的样品，贮存起来供鉴别之用。例如，在相关批次有效期
内需要时，鉴别产品包装形式、包装、标签、供患者用的说明书、批号、失效日期等。 也可能存在
例外情况，不保留重复样本却也能满足上述需求，例如，对一个数量很少的批次进行包装供往不同
市场或所生产的药品非常昂贵。
For finished products, in many instances the reference and retention samples will be presented
identically, i.e. as fully packaged units. In such circumstances, reference and retention samples
may be regarded as interchangeable.
对成品而言，在许多情况下，参考样和留样是相同的，即为完整包装单元。 在此情况下，参考样和
留样可被认为是可以互换的。
2.2 It is necessary for the manufacturer, importer or site of batch release, as specified under
section 7 and 8, to keep reference and/or retention samples from each batch of finished product
and, for the manufacturer to keep a reference sample from a batch of starting material （subject to
certain exceptions – see 3.2 below） and/or intermediate product. Each packaging site should
keep reference samples of each batch of primary and printed packaging materials. Availability of
printed materials as part of the reference and/or retention sample of the finished product can be
accepted.
2.2 依照第 7 条和第 8 条规定，生产商、进口商或批放行场地有必要保留每批成品的参考样和/或留
样，生产商有必要保留每批起始物料（某些例外情况见 3.2）和/或中间产品的参考样。 每个包装场
地应保留每批内包材和印刷包材的参考样。可以接受印刷包材作为成品的参考样和/或留样的一部分
保留。
2.3 The reference and/or retention samples serve as a record of the batch of finished product or
starting material and can be assessed in the event of, for example, a dosage form quality
complaint, a query relating to compliance with the marketing authorisation, a labelling/packaging
query or a pharmacovigilance report.
2.3 参考样和/或留样作为成品或起始物料批次的记录，在发生以下情况时可对其进行评估，例如，
制剂质量投诉、上市许可符合性存疑、标签/包装存疑或药物警戒报告。
2.4 Records of traceability of samples should be maintained and be available for review by
competent authorities.

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2.4 应当保持样品的可追溯性记录，并可供主管部门审查。
3. DURATION OF STORAGE
3．贮存期限
3.1 Reference and retention samples from each batch of finished product should be retained for at
least one year after the expiry date. The reference sample should be contained in its finished
primary packaging or in packaging composed of the same material as the primary container in
which the product is marketed （for veterinary medicinal products other than immunologicals, see
also Annex 4, paragraphs 8 and 9）.
3.1 每批成品的参考样和留样应至少保留到有效期后 1 年。参考样应保存在最终市售成品的内包装中
或与市售成品的内包装容器相同材质的包装中（对于除免疫制剂外的兽药产品，参见附录 4 的第 8
条与第 9 条）。
3.2 Unless a longer period is required under the law of the country of manufacture （whose
competent authority is a PIC/S Member）, samples of starting materials （other than solvents,
gases or water used in the manufacturing process） should be retained for at least two years after
the release of product. That period may be shortened if the period of stability of the material, as
indicated in the relevant specification, is shorter. Packaging materials should be retained for the
duration of the shelf life of the finished product concerned.
3.2 除非生产商（所属监管部门为 PIC/S 成员）所在国的法律要求保留更长时间，起始物料的样品
（除生产过程中使用的溶剂、气体或水外）应至少保留至产品放行后两年。 如果相关质量标准中该
物料的稳定时间较短，则保留时间可以缩短。 包材的留样保留时间应当与相关成品的货架期相同。
4. SIZE OF REFERENCE AND RETENTION SAMPLES
4. 参考样和留样的保留量
4.1 The reference sample should be of sufficient size to permit the carrying out, on, at least, two
occasions, of the full analytical controls on the batch in accordance with the Marketing
Authorisation File which has been assessed and approved by the relevant Competent Authority /
Authorities. Where it is necessary to do so, unopened packs should be used when carrying out
each set of analytical controls. Any proposed exception to this should be justified to, and agreed
with, the relevant competent authority.
4.1 参考样的量应足够，至少能够按照经过相关监管机构审评和批准的上市许可注册资料中的质量控
制要求完成两次全检。 有必要进行检验时，应使用未开启包装的样品进行每组分析控制。 任何不
同于此的例外情况都应当说明理由，并获得相关监管机构的同意。
4.2 Where applicable, national requirements relating to the size of reference samples and, if
necessary, retention samples, should be followed.
4.2 如有关于参考样和留样（如有必要）保留量的适用的国家要求时，应当遵守这些要求。
4.3 Reference samples should be representative of the batch of starting material, intermediate
product or finished product from which they are taken. Other samples may also be taken to monitor
the most stressed part of a process （e.g. beginning or end of a process）. Where a batch is
packaged in two, or more, distinct packaging operations, at least one retention sample should be
taken from each individual packaging operation. Any proposed exception to this should be justified
to, and agreed with, the relevant competent authority.
4.3 所取的起始物料、中间产品或成品的参考样，均应具有代表性。 也可取其它样品，用于监测工
艺中最薄弱的部分（例如某个工艺开始或结束的部分）。 如果一批产品要进行两种或多种不同的包
装，则每种独立的包装操作至少应取一份留样。 任何不同于此的例外情况都应当说明理由，并获得
相关监管机构的同意。
4.4 It should be ensured that all necessary analytical materials and equipment are still available, or

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are readily obtainable, in order to carry out all tests given in the specification until one year after
expiry of the last batch manufactured.
4.4 应确保在生产的最后一批产品有效期后一年内，所有必要的分析材料和设备仍可用或容易获得，
以便对产品质量标准规定的所有项目进行检验。
5. STORAGE CONDITIONS
5. 贮存条件
5.1 […] *
5.2 Storage conditions should be in accordance with the marketing authorisation （e.g. refrigerated
storage where relevant）.
5.2 贮存条件应符合上市许可（例如，相关的冷藏）。
6. WRITTEN AGREEMENTS
6. 书面协议
6.1 Where the marketing authorisation holder is not the same legal entity as the site（s）
responsible for batch release, the responsibility for taking and storage of reference/retention
samples should be defined in a written agreement between the two parties in accordance with
Chapter 7 of the PIC/S Guide to Good Manufacturing Practice. This applies also where any
manufacturing or batch release activity is carried out at a site other than that with overall
responsibility for the batch and the arrangements between each different site for the taking and
keeping of reference and retention samples should be defined in a written agreement.
6.1 当上市许可证持有人与负责批放行的场地不是同一个法人实体时，应按照 PIC/S GMP 指南第 7
章的要求，在双方签订的书面协议中规定参考样/留样的取样和贮存责任。 当任何生产或批放行活动
所在场地不是对该批负有全面责任的场地时，同样应该有书面协议规定每个不同场地之间参考样和
留样的取样和贮存的安排。
6.2 The Authorised Person who certifies a batch for sale should ensure that all relevant reference
and retention samples are accessible at all reasonable times. Where necessary, the arrangements
for such access should be defined in a written agreement.
6.2 负责认证批次供销售的质量受权人应确保在合理时间内，能获得全部相关参考样和留样。必要时，
应在书面协议中对参考样和留样的获取做出规定。
6.3 Where more than one site is involved in the manufacture of a finished product, the availability
of written agreements is key to controlling the taking and location of reference and retention
samples.
6.3 当成品的生产涉及一个以上场地时，书面协议是控制参考样和留样取样和贮存的关键。
7. REFERENCE SAMPLES – GENERAL POINTS
7. 参考样-概述
7.1 Reference samples are for the purpose of analysis and, therefore, should be conveniently
available to a laboratory with validated methodology. For starting materials and packaging
materials used for medicinal products, this is the original site of manufacture of the finished
product. For finished products, this is the original site of manufacture.
7.1 参考样的目的是用于分析，因此，其存放地点应当便于有经过验证的方法的实验室获取。生产药
品所用的起始物料和包材，其参考样应存放在成品的初始生产场地。成品的参考样应存放在初始生
产场地。
7.2 […] *
8. RETENTION SAMPLES – GENERAL POINTS
8. 留样-概述
8.1 A retention sample should represent a batch of finished products as distributed and may need

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to be examined in order to confirm non-technical attributes for compliance with the marketing
authorisation or national legislation. The retention samples should preferably be stored at the site
where the Authorised Person （AP） certifying the finished product batch is located.
8.1 留样应代表销售的成品批次，且可能需要对留样进行检查，以确认非技术方面的属性是否符合上
市许可或国家法律法规要求。留样最好存放在质量受权人认证成品批放行的场地。
8.2 […] *
8.3 Retention samples should be stored at the premises of an authorised manufacturer in order to
permit ready access by the Competent Authority.
8.3 留样应贮存在经批准的生产企业的场地内，以方便监管机构获取。
8.4 Where more than one manufacturing site is involved in the manufacture
importation/packaging/testing/batch release, as appropriate of a product, the responsibility for
taking and storage of retention samples should be defined in a written agreement（s） between
the parties concerned.
8.4 当产品的生产进口/包装/检验/批放行等涉及一个以上生产场地时 , 应在相关各方签订的书面协议
中规定留样的取样和贮存的责任。
9. REFERENCE AND RETENTION SAMPLES FOR PARALLEL IMPORTED / PARALLEL
DISTRIBUTED PRODUCTS
9．平行进口/平行分销产品的参考样及留样
Note: This section is only applicable if the national legislation deals with parallel imported / parallel
distributed products.
注: 仅在国家立法涉及平行进口/平行分销产品时才适用本节。
9.1 Where the secondary packaging is not opened, only the packaging material used needs to be
retained, as there is no, or little, risk of product mix up.
9.1 若外包装未被打开 , 只需要对所用包材留样 , 因为这种情况下没有或几乎没有产品混淆的风险。
9.2 Where the secondary packaging is opened, for example, to replace the carton or patient
information leaflet, then one retention sample, per packaging operation, containing the product
should be taken, as there is a risk of product mix-up during the assembly process. It is important to
be able to identify quickly who is responsible in the event of a mix-up （original manufacturer or
parallel import assembler）, as it would affect the extent of any resulting recall.
9.2 如果外包装被打开，例如，为了替换包装盒或患者说明书而打开外包装 , 因在重新组合过程中有
产品混淆的风险 , 故应每个包装操作进行一次留样（包含产品）。 在出现混淆的情况下 , 能迅速识
别相关的责任人（原始生产商或平行进口再包装商）极为重要 , 因为这将影响产品召回所涉及的范
围。
10. REFERENCE AND RETENTION SAMPLES IN THE CASE OF CLOSEDOWN OF A
MANUFACTURER
10. 生产商倒闭情况下的参考样与留样
10.1 Where a manufacturer closes down and the manufacturing authorisation is surrendered,
revoked, or ceases to exist, it is probable that many unexpired batches of medicinal products
manufactured by that manufacturer remain on the market. In order for those batches to remain on
the market, the manufacturer should make detailed arrangements for transfer of reference and
retention samples （and relevant GMP documentation） to an authorised storage site. The
manufacturer should satisfy the Competent Authority that the arrangements for storage are
satisfactory and that the samples can, if necessary, be readily accessed and analysed.
10.1 当某生产商倒闭 , 及生产许可证被撤销、吊销或终止时 , 由其生产的很多尚未过期的药品批次
极有可能仍在市场上销售。对于这些仍在市场流通的产品批次, 生产商应作出详细安排 , 以便将对应

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的参考样和留样（及相关 GMP 文件）转移给经批准的贮存场地.该生产商的安排应使监管机构相信 ,
贮存是合适的并且在必要时易于取得样品进行检验。
10.2 If the manufacturer is not in a position to make the necessary arrangements this may be
delegated to another manufacturer. The Marketing Authorisation holder （MAH） is responsible
for such delegation and for the provision of all necessary information to the Competent Authority. In
addition, the MAH should, in relation to the suitability of the proposed arrangements for storage of
reference and retention samples, consult with the competent authority of each country in which any
unexpired batch has been placed on the market.
10.2 如果生产商不能做出必要的安排 , 则可以委派另一生产商负责此项工作。上市许可证持有人
（MAH）负责此项委派工作，同时也负责向监管机构提供所有必要的信息。此外，关于参考样和留
样贮存安排的适宜性，MAH 应咨询每一个尚有未过期产品流通的国家的监管机构。
10.3 […] *
*This Section is specific to the EU GMP Guide and has not been adopted by PIC/S.
*本节专门针对欧盟 GMP 指南，尚未被 PIC/S 采用。

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