1. SCOPE   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.   

本附录为《药品生产质量管理规范指南》（简称"GMP指南"）提供关于起始物料、包装材料或成品的对照样品取样与保存，以及成品留样的指导。   

1.2 Specific requirements for investigational medicinal products are given in Annex 13 to the Guide.   

关于临床试验用药品的具体要求，请参见指南附录13。   

1.3 This annex also includes guidance on the taking of retention samples for parallel imported/distributed medicinal products.   

本附录还包括对平行进口/分销药品留样的指导。   

2. PRINCIPLE   原则   

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:   

样品留样需满足两个目的：第一是为分析检测提供样品，第二是为成品提供实物样本。因此，样品可分为两类：   

• 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.   

对照样品：从一批起始物料、包装材料或成品中抽取的样品，储存起来以便在有关批次的保质期内有需要时进行分析。在稳定性允许的情况下，应保存关键中间阶段（如需要分析测试和放行的中间阶段）的对照样品或在制造商控制范围外运输的中间样品。   

• Retention sample: A sample of a fully packaged unit from a batch of finished product. It is stored for identification purposes (e.g., presentation, packaging, labelling, patient information leaflet, batch number, expiry date) should the need arise during the shelf life of the batch concerned. Exceptional circumstances where duplicate samples may not be required include small batches packaged for different markets or very expensive medicinal products. In such cases, reference and retention samples may be interchangeable if identically presented.   

留样：成品批次中完整包装单元的样品，用于在效期内需要时确认产品属性（如外观、包装、标签、说明书、批号、有效期）。例外情况包括：小批量分装至不同市场或极昂贵药品，此时若样品形式一致，对照样品与留样可互换。   

2.2 Manufacturers, importers, or batch release sites (as specified in sections 7 and 8) must retain reference and/or retention samples from each batch of finished product. Manufacturers must also retain a reference sample from batches of starting materials (subject to exceptions in 3.2) and/or intermediate products. Each packaging site should retain reference samples of primary and printed packaging materials. Printed materials may be included as part of the finished product’s reference/retention sample.   

制造商、进口商或批放行场所（见第7、8章）必须为每批成品保留对照样品和/或留样。制造商还需为起始物料批次（见3.2例外情况）和/或中间产品保留对照样品。各包装场所应保存内包材和印刷包材的对照样品，印刷材料可作为成品参考/留样的一部分。   

2.3 Reference and/or retention samples serve as a record of the batch and can be assessed in cases such as quality complaints, compliance queries, labelling issues, or pharmacovigilance reports.   

对照样品和/或留样可作为批次的记录，并可在质量投诉、合规性查询、标签问题或药物警戒报告等情况下进行评估。

2.4 Traceability records of samples must be maintained and made available for review by competent authorities.   

样品的可追溯性记录必须保存，并供监管机构审查。   

3. DURATION OF STORAGE   储存期限   

3.1 Reference and retention samples from each batch of finished product must be retained for at least one year after the expiry date. Primary packaging or equivalent material must be used for storage (veterinary products excepted; see Annex 4, paragraphs 8–9).   

每批成品的对照样品和留样必须至少保存至有效期后一年。储存容器应与上市产品一级包装材质一致（兽药除外，详见附录4第8-9段）。   

3.2 Starting material samples (excluding solvents, gases, or water) must be retained for at least two years post-release, unless national law or material stability specifications require a longer period. Packaging materials must be retained for the shelf life of the finished product.   

起始物料样品（溶剂、气体或水除外）必须保存至放行后至少两年，除非本国法律或物料稳定性要求更长期限。包装材料需保存至成品有效期结束。   

4. SIZE OF REFERENCE AND RETENTION SAMPLES   

4. 对照样品与留样的数量   

4.1 Reference samples must be sufficient for two full analytical tests per Marketing Authorisation requirements. Unopened packs should be used where possible; exceptions require competent authority approval.   

对照样品数量应满足上市许可要求的两次全检需求。尽可能使用未开封包装；例外情况需经监管机构批准。   

4.2 National requirements for sample sizes must be followed.   

样品数量需符合本国法规要求。   

4.3 Samples must be representative of the original batch. Additional samples may be taken from process-critical stages (e.g., start/end of production). For batches with multiple packaging operations, at least one retention sample must be taken from each operation; exceptions require approval.   

样品对原始批次必须具有代表性。可在工艺关键阶段（如生产起始/结束）额外取样。多步骤包装的批次，每一步骤至少取一个留样；例外情况需批准。   

4.4 Analytical equipment and materials must remain available for one year post-last batch expiry.   

分析设备和试剂需在末批有效期后一年内可用。   

5. STORAGE CONDITIONS   

5. 储存条件   

5.1 [···]*   

带*章节为欧盟GMP指南特有内容，PIC/S未采纳。下同。

5.2 Storage must comply with Marketing Authorisation requirements (e.g., refrigeration if specified).   

储存条件须符合上市许可要求（如规定需冷藏）。   

6. WRITTEN AGREEMENTS   

6. 书面协议   

6.1 If the marketing authorisation holder differs from the batch release site, responsibilities for sample retention must be defined in a written agreement (per PIC/S GMP Chapter 7). This applies to all multi-site manufacturing/batch release scenarios.   

若上市许可持有人与批放行场所分离，需通过书面协议（遵循PIC/S GMP第7章）明确样品保留责任。此要求适用于所有多场地生产/放行场景。   

6.2 The Authorised Person (AP) must ensure samples are accessible at all reasonable times; agreements should outline access arrangements.   

受权人（AP）须确保样品在合理时间内可获取；协议中应明确访问权限。   

6.3 Written agreements are essential for multi-site finished product manufacturing/importation.   

多场地成品生产/进口时，书面协议至关重要。   

7. REFERENCE SAMPLES – GENERAL POINTS   

7. 对照样品通用要求   

7.1 Reference samples must be stored at the original manufacturing site (for starting materials/intermediates) or finished product site to facilitate analysis by qualified laboratories.   

对照样品须储存在原始生产场所（起始物料/中间体）或成品生产场所，以便具备资质的实验室检测。   

8. RETENTION SAMPLES – GENERAL POINTS   

8. 留样通用要求   

8.1 Retention samples should reflect the distributed batch and be stored at the site of the Authorised Person (AP) certifying the batch.   

留样应反映已分销的批次，并存放在认证该批次的受权人 (AP) 所在地。   

8.2 [···]*   

8.3 Samples must be stored at an authorised manufacturer’s premises for Competent Authority access.   

样品须储存在经授权的生产商场所，便于监管机构调取。   

8.4 For multi-site manufacturing/importation, written agreements must define sample responsibilities.   

多场地生产/进口时，协议须明确样品责任归属。   

9. REFERENCE AND RETENTION SAMPLES FOR PARALLEL IMPORTED/DISTRIBUTED PRODUCTS   

9. 平行进口/分销产品的对照样品与留样   

*Applies only if national legislation permits parallel imports/distribution.*   

*仅适用于允许平行进口/分销的本国法规*   

9.1 If secondary packaging remains unopened, only packaging materials need be retained (low risk of mix-up).   

若外包装未开封，仅需保留包材（混淆风险低）。   

9.2 If secondary packaging is opened (e.g., to replace cartons or leaflets), one retention sample per packaging operation must be taken (to identify responsibility in case of mix-ups).   

若外包装已开封（如更换纸盒或说明书），每一步包装操作均需取一个留样（以便混淆时追责）。   

9.3 Recall scope depends on whether the original manufacturer or parallel importer caused the mix-up.   

召回范围取决于是原制造商还是平行进口商造成的混淆。   

10. REFERENCE AND RETENTION SAMPLES IN CASE OF MANUFACTURER CLOSURE   

10. 生产商停产时的对照样品与留样   

10.1 If a manufacturer ceases operations, arrangements must be made to transfer samples and GMP documentation to an authorised storage site. The MAH must ensure storage adequacy and notify competent authorities.   

生产商停产后，须将样品和GMP文件转移至授权储存场所。MAH须确保储存合规并向监管机构通报。   

10.2 If the manufacturer cannot arrange storage, another manufacturer may be delegated by the MAH, who remains responsible for compliance.   

若生产商无法安排储存，MAH可委托其他生产商，但MAH仍对合规性负责。   

10.3 [···]*   

Note: Sections marked with * are specific to the EU GMP Guide and not adopted by PIC/S.