重新包装管理规程(1)

评估内容 是否涉及变更控制，是否需要开启■NA 或已开启变更来评估制修订产生的影响。 是否符合法规及注册标准要求。 ■NA ■GMP□药典□国标□ISO □其他标准 ■是 □否 □其他： □是 ■否 □其他（如变更号）： 评估结果 备注 是否涉及铅印（订做/请购） □是 ■否 如是，则列出所需铅印的内容 是否有记录需设置到电子系统中使□是 ■否 用（如：ERP/数据库） 如是，则列出所涉及的附录 是否合并规程 □是 ■否 如是，则列出所涉及的规程 ■NA 是否需要采取其它行动 □是 ■否 □其他： □价值流原液部 □价值流制剂部 分发部门 ■价值流供应部 □价值流质量保证 □环境健康安全部 □产品放行 □质量控制 □质量改进项目部 □科学技术部 □技术支持部 □质量体系 □质量验证 □其他：

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目 录

第一部分 正文

1.目的 ·········································································································· 第 3页 2.适用范围 ····································································································· 第3 页 3.责任部门（人） ··························································································· 第4-5 页 4.定义和缩略语 ······························································································ 第5-6 页 5.物料和设备 ··································································································· 第6 页 6.规程 ······································································································ 第6-12 页 7.附件 ········································································································ 第12 页 8.附录 ········································································································ 第12 页 9.参考文件 ································································································ 第12-13页 10.注意事项 ·································································································· 第13 页 第二部分 正文附件

附件A····································································································· 第14-15 页

●产品重新包装管理规程 Product Reprocessing and Repackaging Management

1. 目的 Objective / Purpose

1.1 明确返工和重新包装的定义Definition of Reprocessing and Repacking

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1.2 明确返工要求和重新包装操作的管理流程、职责Define Reprocessing requirement and the process and responsibility of Repackaging. 2. 适用范围Scope

2.1重新包装范围见下表1：The scope of Repackaging is listed in table 1 below:

2.2 TY所有的商业产品均不得进行返工、重新加工；Reprocessing and reworking is not allowed for all commercial product in Tianyuan manufacturing site. 工艺过程中适用与不适用重新包装的类型详见下表1：

The table below details the types of repacking to which the process does or does not apply.：

重新包装种类Types of Repacking 适用于Applies To 所有第二次包装操作均发生在成品已经过QP放行或其他同等批次放行流程放行后，和/或该产品已离开原始生产地后，具体内容包括： All Secondary Packing Operations that take place after the finished product has been released following QP certification or equivalent batch release process and/or has left the original manufacturing site, including: ✓ 外包装材料的变更，添加，替代和/或去除Alteration, addition, substitution and/or removal of secondary packaging ✓ 组分（例如：说明书，内盒）Components (For 不适用于Does Not Apply To 禁止在西林瓶，安瓿瓶，注射器及任何疫苗产品的初次包装上打印或覆盖贴标。任何重新包装发生在成品放行之前和/或离开原始生产地之前，具体内容包括： Printing or over-labeling on vials, ampoules, syringes and any vaccines product primary packaging as this is prohibited. Any repacking, which takes place before the finished product has been released and/or has left the original manufacturing site, This includes: o 任何工序涉及内包装材料破坏（或无菌生物制品包装开口/破损）Any process that involves the breaking of the primary pack (or blister opening/breaching for sterile and biological products). o 质量许可情况下，在某一工厂对半成品做进一步处理可编辑

精品文档 example: leaflets, cartons). ✓ 添加防篡改或防伪标志Addition of tamper evident or ant counterfeit features. ✓ 由于产品需从一个市场转移到其他市场，重新包装或重新贴标签以符合当地语言要求。Repacking or relabeling to meet local language requirements as a result of transfer of product form one market to anther market （贴标或包装）Semi-finished product further processed by a site (labeling and packaging) and for which the activity is covered in Quality Agreement. o 产品放行上市之前在原生产地进行的成品重新包装Repacking of finished packs at original packing site before the product is released for sale. o 在产品内盒外添加VVM标签Add the VVM labeling on the carton. ✓ 初次包装后已放行到市场Packaging of primary packs released to the market.。

3. 责任部门（人）Responsible department (person) 关键的角色和职责KEY ROLES AND RESPONSIBILITIES

以下个人和团队有重要的角色和职责来完成重新包装流程。同一个人可能担任不止一个角色，保留必要的批准职责 The following individuals and teams have key roles and responsibilities to fulfill in the Repacking process. The same individual may perform more than one role, provided the necessary independence of required approvals is maintained. 商业角色Business Role 重新包装发起人评估重新包装，确保评估是基于商业，监管，市场及产品质量要求。To assess the 关键职责Key Responsibilities Repacking Proposer repacking activity and ensure it is justified based on commercial, regulatory, market and product quality requirements. 评估报告在重新包装开始前得到批准To obtain appropriate approval for the 可编辑

精品文档 repacking before it starts. 确保重新包装活动是有记录追踪的。To ensure that repacking activity is captured in a local tracker. 质量部-Quality QAVS 确保重新包装的流程是有效的和健全的，重新包装符合该SMP要求。To ensure effective and robust processes are in place and in use to manage repacking, in accordance with this SMP. 审阅和批准重新包装申请 To review and approve repacking proposals. 在重新包装开始之前获得适当额外的批准 To obtain appropriate additional approvals for the repacking before it starts. 确保重新包装的设施能满足用途，例如符合要求，文件，设备及人员充足 To ensure that repacking facilities are fit for purpose, i.e. comply with requirements and adequate documentation, equipment and personnel are in place. 确保任何发起的重新包装的法规影响经过评估和记录，否则委托给重新包装者或原始制造地（必要时QS支持） To ensure that any regulatory implications of any proposed repacking have been assessed and addressed. Unless delegated to the repacker or original manufacturing site. 批准或拒绝与药品相关的重新包装的要求 To approve or reject repacking requests related to medicinal products. 可编辑

精品文档 放行QA/QP QP/QA Release 审阅和批准重新包装申请（二级）To review and approve repacking proposals. 确保所有重新包装的组分是完全受控的 To ensure all repacking components are adequately controlled. 在年度APR中回顾重新包装的批次 To periodically review repacking batch in the APR Report . 放行重新包装的材料（放行QA） To release components for repacking (QA Release) 批准或拒绝与药品相关的重新包装的要求（二级）To approve or reject repacking requests related to medicinal products . 按照法规要求放行重新包装产品 To release repacked products where required by regulations. 仓库管理员 Warehouse Handler 把所重新检查和重新包装的批号分开存放 Segregate physically the recheck and repack batches and indicate in the inventory logbook.. 4. 定义和缩略语 Definition and abbreviation

重新包装：任何内包装材料或者外包装材料的文字的更改,，或去除或替换任何已打印外包装材料，并且操作均发生在成品已按照QP放行或其他同等批次放行流程放行后，和/或该产品已离开原始生产地后。 Any operation that:

Requires the alteration of text to primary or secondary packaging and/or the addition, removal or exchange of any printed secondary packaging material, and takes place after the finished product has been released following QP certification or equivalent batch release process and/or has left the original manufacturing site.

5. 物料和设备 Materials and equipment N/A

6. 规程 Procedure

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6.1 重新包装

6.1.1重新包装评估（参见附录1）Assessment of Repacking

重新包装申请者必须评估重新包装开始之前所有行动是否合理，要求：The Repacking Proposer must assess if repacking is justified before starting any repacking activities. They must: 6.1.1.1评估重新包装的理由 Evaluate the reason(s) why repacking is required.

由于偏差而需要重新包装时，确认必要的纠正预防措施已经完成 When required because of a deviation, confirm that necessary corrective and preventative actions (CAPAs) are complete.

6.1.1.2评估申请的重新包装的商业可行性，需考虑重新包装批次的成本，供应的重要性及再包装产品剩余保质期 Evaluate commercial viability of proposed repacking, taking into account total cost, criticality of supply and extent of shelf life remaining for any repacked batches.

6.1.1.3定义范围，比如包装需要改变，包装的数目 Identify what would be involved, for example changes to be made to the pack, number of packs to be processed.

6.1.1.4评估在什么地方进行重新包装操作，确认以下内容被批准 Evaluate where the repacking operations would be conducted and confirm that the following are in place and approved:

A: 供应的技术项目 Technical terms of supply .

B: 对于第三方，第三方操作现场审计，技术/质量方协议和合同 For third parties, Site audit for proposed activity, technical/quality agreements and contracts.

6.1.1.5识别待供应的市场，法规及批次放行的影响 Identify markets to be supplied, regulatory and batch release implications.

6.1.1.6识别任何重新包装操作过程中需要的环境控制，如在非冷藏条件下的储存时间 Identify any environmental controls required during repacking operations, for example time out of cold store. 6.1.1.7 识别任何与申请的重新包装相关的风险及任何的缓解行动 Identify any risks associated with proposed repacking together with any mitigation plans.

6.1.1.8 确认防篡改或防伪标志是否会被破坏或者是否需要重新添加 Determine whether tamper evident

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or anti-counterfeit features would need to be broken, or are required, and whether they must be reapplied or added.

6.1.1.9 确认任何额外的测试或抽样的要求 Identify any additional testing and sampling requirements 6.1.1.10 确认批号的要求SOP.QM.00.04.001. Identify batch number requirements See SOP.QM.00.04.001.

6.1.1.11 确保任何重新包装被当地的法规部门批准（如果需要）。重新包装的申请人必须在重新包装申请单中记录此评估以及重新包装的理由。必须记录清晰，详述重新包装的流程，包括任何重新包装操作的控制要求。然后评估报告须提交给质量进行批准 Ensure that any repacking is approved by local Regulatory Authorities if local regulations require it.

The repackaging proposer must document this assessment and rationale for why the repacking is justified in a repacking request form. They must also document clear, detailed repacking instructions including the controls required for any proposed repacking operation. They must then submit the form to Quality for approval. 一级评估包括 Level 1 assessment include： 二级评估除了上述内容外，还包括： Level 2 assessment includes these items as below besides those in level 1: 1.重新包装的原因，为什么需要重新包装，出错的原因在哪里，是否己有针对这一原因的CAPA 。The reason why the repack is required and where required as a result of an error, and confirm that the necessary CAPA have been addressed.。 2. 对法规和批放行的影响Impact on regulatory 1. 在哪里进行重新包装.所有涉及产品组分或者打印变化的重新包装必须在浙江天元生物药业有限公司进行。Repack location. All the repack operations related with component or overprinting changing must be executed in TY, accept price label sticking. 2. 如为退货产品，应检查、检验和调查， 并有证据可编辑

精品文档 and batch release. 3. 对产品质量的影响，如冷链条件包装完整性的影证明退货产品质量未收影响， 且经质量管理部门根据操作规程评价后，方可考虑将退货重新包装、重新发运销售。评价考虑的因素至少应当包括药品的响、混淆的风险、物料平衡的影响等 性质、所需的贮存条件、药品的 现状、历史，以及Impact on product quality. Such as impact on 发运与退货之间的间隔等因素。不符合贮存和运输cold chain, packing integrity, mix-up and 要求的退货应当在质量管理部门的监督下予以销reconciliation. 4. 对追溯性的影响。哪些需要重新包装，如重新包装则需要做哪些变动，重新包装的数量等 Impact on traceability. Which portion need to be rechecked and repacked, any change need to be done if there is repacking, and the quantity need to be rechecked and repacked . 5. 确定防窃起特征是否需要破坏，添加， 或重新使用 To confirm if temper feature need to be broken, added or re-used. 6. 重新包装的商业可行性，总费用和对供应的影响 quality of return goods, they should not be Impact on commercial viability, total cost and shipped out. criticality of supply. 7. 重新包装仍沿用以前的批号信息Batch number will not be changed for repacking. 3. 文稿变更Artwork change 4. 识别重新包装可能引起的其他风险及其缓解措施 毁。对退货质量有怀疑时，不得重新发运。 If the returned goods are going to be repacked, they should be checked, tested and investigated to prove that the quality is not impacted. It should be assessed by quality department before return goods being repacked and shipped out. The assessment should at least includes the product characters, storage conditions, the status and history of the products and time between shipment and return. Goods that cannot meet requirement should be destroyed. If there is any hesitate on 可编辑

精品文档 8. 留样Determine retention samples Identify any risk associated with the proposed rechecking and repacking together with any mitigation plans. Note ：本SOP范围之外的情况在实施之前须得到总部机构的批准In case there is other recheck or repack case out of the scope of this SOP. Approved by quality groups prior to commencing recheck and repack

6.1.2 图案文稿及原材料批准 Artwork and Materials Approval

如果需要重新创建新的图案文稿，则所有的与重新包装组分相关的打印材料和图案文稿必须采用图案文稿控制程序进行批准（SOP.QM.00.02.006）If there is a requirement to create new artwork then all printed materials and artwork relating to repacking components must be approved using Artwork Control Process (refer to SOP.QM.00.02.006)

6.1.3重新包装批准 Repacking approval

质量部必须至少基于以下准则批准或拒绝评估 Quality must approve or reject the assessment based upon the following criteria as a minimum:

6.1.3.1重新包装不涉及在西林瓶、注射器或疫苗产品上覆盖打印或增加标签 The repacking does not involve overprinting or adding labels to vials, syringes or any vaccines products.

6.1.3.2任何与重新包装产品相关的纠正预防措施已经完成。重新包装的厂房设施已根据GSK审计要求被批准用于重新包装操作 Any CAPAs, relating to product being repacked are complete. Repacking facilities are approved for the type of repacking operation proposed, following GSK audit.

6.1.3.3重新包装的厂房设施相关供应或质量协议和合同的技术条款已准备就绪，以及与重新包装操作的类别 Technical Terms of Supply/Quality Agreements and contracts with repacking facilities are in place and relate to the type of repacking operations to be performed.

6.1.3.4 法规及批次放行要求能够满足 Regulatory and batch release requirements for the market can

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be met.

6.1.3.5 与申请的重新包装的操作相关的风险包括环境控制和防篡改标已被充分评估及相应的降低风险的处理措施可接受 Risks, including environmental controls and tamper evidence, associated with proposed repacking operations have been fully evaluated and any countermeasures proposed to mitigate risks are acceptable.

6.1.3.6 批号，包装及包装的组分是匹配的及可追溯的 Batch number, pack and pack components are suitable and traceable.

6.1.3.7 额外的测试和抽样要求是符合重新包装需求、操作和法规要求 Additional testing and sampling requirements are appropriate for the product type, repacking operation and market regulatory requirements.

6.1.3.8 重新包装是否需要额外的质量批准，需考虑以下几点： if the repacking requires additional quality approval, taking into account the following: ✓ 正在重新包装的产品 Product being repacked . ✓ 重新包装行动的性质 Nature of the repacking activity.

✓ 重新包装的地点（例如 GSK 工厂或第三方工厂）Where the repacking is done (i.e. GSK site or third

party facility)

以下表格详述了不同的批准要求。如果某种特殊的重新包装行动没有在这个表格列举则采取最高的批准标准The table below details the different approval requirements. If a specific repacking activity is not listed in this table, apply the highest level of approval. Table 1 – Approval levels for repacking activities

活动Activity 组分更换/增加/移除-如说明书，外包装材料第二层包装Exchange/addition/removal of component(s) -leaflets, secondary packs 可编辑

级别 Level 2 精品文档 增加防篡改和防伪 Addition of tamper evident or anti-counterfeiting features 增加标签：不涉及注册内容 Addition of labels that do not obscure / change registered text 使用说明 Key to table 1 :

1-价值流质量保证负责人批准 Approval by QAVS Lead.

2-价值流质量保证负责人和QP批准 Approval by QAVS Lead and QP. 6.1.4 重新包装 Repacking

6.1.4.1重新包装准备 Preparing for repacking

1 1 质量部必须确保以下用于重新包装的要求达成：Quality must ensure that the following is in place and used for the repacking operation:

✓ 适合的受控制区域 a suitable controlled area；

✓ 批准的重新包装程序，包括额外标签或打印信息不会对原始信息产生影响。(如:剂量信息、有效期、批号

或其他注册细节 ) approved repacking instructions, including where to apply any additional labels or printing to not obscure primary information (For example: dosing information, expiry

date, batch number or other registered details）； ✓ 人员培训trained personnel；

✓ 印刷信息被批准的供应商打印并放行使用，并可以追溯，图案文稿参见SOP.QM.00.02.006 components

generated using approved artwork see SO P.QM.00.02.006,printed by an approved supplier released for use, and fully traceable；

✓ 定义合适的/物料平衡定义 defined reconciliation limits, suitable for the proposed repacking. 6.1.4.2 实施重新包装 Carrying out repacking

6.1.4.2.1必须确保重新包装操作符合相应的程序：Quality must ensure that the repacking process complies with procedures applicable to the repacking activities, including:

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✓ 环境控制，比如移出冷库后最大放置时间（TOR）Special environmental controls, for example

maximum time out of cold store（TOR）.

✓ 重新包装操作中间控制 In-process controls appropriate to the repacking operation in place. ✓ 区域、包装线清场参见SOP.PR.07.05.008/SOP.PR.00.05.026，需包括新包装材料进入前，原有的包装材

料的从包装现场移出（例如：更换说明书或包装盒）Area/line clearance see

SOP.PR.07.05.008/SOP.PR.00.05.026 , which must include clearance of components removed from a pack (For example: changing a leaflet or carton), before new components are introduced. ✓ 安全处理被代替的和废弃包装材料 Secure disposal of replaced and waste packaging components

See SOP.QM.00.04.015.

✓ 检测和采样要求Testing and Sampling requirements. 6.1.4.2.2必须确保 They must also ensure that:：

✓ 所有包装活动是有追溯的 Traceability of all packs is maintained.

✓ 重新包装产品的有效期不能改变 Expiry date of the repacked batches is unchanged.

✓ 用于重新包装的材料样本需包含在批记录中 Samples of component(s) used in the repacking are

included in the batch documentation.

✓ 法定留样需根据当地法规要求管理 Retained samples are appropriately managed according to local

legislation.

重新包装第一时间，申请人和质量部门必须批准第一包装品（样本）。后续操作可以基于首个包装品照片进行Whenever conducting a repacking for the first time, the Repacking Proposer and Quality must approve the first pack (prototype). They can do so based on photographs of the first pack sent by the repacker.

6.1.5 重新包装后 Post repacking

The repacking proposer must record the complete history of the repacking activities. 重新包装发起部

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门必须记录重新包装活动的完成过程。

6.1.6 批次放行 Batch release

6.1.6.1重新包装批次（或批次部分）放行前，为追踪重新包装的物料状态，质量部必须评估重新包装的各个方面 Before releasing a repacked batch (or part batch), Quality must assess all aspects of repacking in order to progress the status of the repacked material.

6.1.6.2 需符合批次放行管理程序，参见SMP.G.00.QM.029，并审核批文件信息以确认批次适合上市。 In accordance with batch release procedures， see SMP.G.00.QM.029 review the batch documentation and information available to confirm that the batch is suitable for sale.

6.1.7 审核 Review

年度APR回顾中回顾重新包装的批次，以及重新包装操作过程中产生的额外行动，比如偏差、纠正预防措施是否都已经执行。（参见SMP.G.00.QM.015）

The repacked batches and additional actions during repacking (e.g. deviation and CAPA actions implementation status) need to be reviewed in APR.（See SMP.G.00.QM.015）.

7. 附件Attachment

附件序号 Number 附件名称 Name 附件A Attachment A

重新包装流程 Repackaging Process 8. 附录 Appendix

附录序号附录名称 附录编号/版本号 状态（多选） 可编辑

精品文档 Number 附录1 Appendix 1 附录2 Name Number/version Status 返工登记台账 GER.SMP.G.00.PR.028-01/05 新建□ 更新□ 未更新□ 废除■ 已废除□ 电子形式受控□ NA□ 产品返工管理规程考核试Appendix 卷 2 附录3 Appendix 3 附录4 Appendix 4

9. 参考文件 Reference documents 9.1. 制订依据：GQMP5010 9.2. 相关规程：

产品重新包装管理规程考核试卷 GER.SMP.G.00.PR.028-04/01 产品重新包装评估表 GER.SMP.G.00.PR.028-03/01 GER.SMP.G.00.PR.028-02/05 新建□ 更新□ 未更新□ 废除■ 已废除□ 电子形式受控□ NA□ 新建■ 更新□ 未更新□ 废除□ 已废除□ 电子形式受控■ NA□ 新建■ 更新□ 未更新□ 废除□ 已废除□ 电子形式受控■ NA□ SMP.G.00.QM.015 年度产品质量回顾管理规程；SMP.G.00.QM.015 Product Quality Annual Review management procedure

SMP.G.00.QM.029 放行管理规程；SMP.G.00.QM.029 Product release management procedure SOP.QM.00.04.001 产品及物料批号编制SOP；SOP.QM.00.04.001 Batch numbering operation procedure

SOP.PR.00.05.009 产品重新包装SOP；SOP.PR.00.05.009 Product repackaging operation procedure SOP.PR.07.05.009 重组乙型肝炎疫苗（酿酒酵母）重新检查和重新包装SOP；SOP.PR.07.05.009 Recheck and

可编辑

精品文档

repackaging operation procedure for Engerix vaccine

SOP.QM.00.02.006 包装材质设计审批SOP；SOP.QM.00.02.006 Packaging material design approval procedure

SOP.PR.07.05.008重组乙型肝炎疫苗（酿酒酵母）清场确认操作SOP；SOP.PR.07.05.008 Line clearance procedure for Engerix vaccine

SOP.PR.00.05.026 包装车间各工序清场SOP；SOP.PR.00.05.026 Line clearance procedure

SOP.QM.00.04.015 分包装车间残次产品转移、残次包装材料处理SOP； SOP.QM.00.04.015 Filling and packaging rejects transfer procedure.

10. 注意事项 Notes

10.1 重新包装产品批号及有效期不得发生改变；The expiry date and batch number shall not be changed for repacked product.

10.2 如果需要规程以外的批准可参加GQMP5010的要求进行审批；If additional approval is required, refer to GQMP5010.

附件A：重新包装流程 Repackaging Process 步骤 1 决策 指向1 关键决策1 重新包装是否是合理的？ 输出 是的：重新包装评估记录在相关文件中 否：拒绝 重新包装评估 关键决策2 步骤 2 批准重新包装需 决策 指向2 可编辑 有要求制定图案文稿或促销内容的材料吗？ 输出 精品文档

步骤 3 决策 指向3 关键决策3 重新包装评估被QAVS/QP批准 批准重新包装评估 （QAVS/QP） 步骤6 重新包装批次回顾 步骤 5 产品放行 步骤 4 重新包装 输出 是的：(继续下一步 )/ 否： (拒绝) 关键决策5 重新包装的记录是完整的和合格的吗？ 决策 指向5 Output 输出 是的：放行重新包装的批次 否：拒绝 决策 指向6 关键决策6 定期回顾重新包装批次（APR） 输出 识别重新包装批次是否有额外的偏差或CAPA未执行 附件A：重新包装流程 Repackaging Process STEP 1 Assessment of repacking Key Decision point 1 Is packing justified? Output Yes, repacking assessment documented in relevant form NO, reject Decision Point 1 STEP 2 Develop and approve Key Decision Point 2 Decision Point 2 Is it required to develop materials with artwork or promotional content? Output Yes ,develop and approve materials according to LOC process ,than proceed to step3 No , go to step 3 可编辑 materials used for repacking 精品文档

STEP 3 proval by QAVS or QP Decision Point 3 STEP 4 Repack Key Decision Point 3 Repacking approved by QAVS or QP Output Yes (proceed )/ No (reject) STEP 5 Batch release Key Decision Point 5 Decision Point 5 Are the repacking records complete and satisfactory? Output Yes: release repacked batch No: assess deviations or reject STEP 6 Decision Point 6 Key Decision Point 6 The repacked batches and additional actions during repacking (e.g. deviation and CAPA actions implementation status) need to be reviewed in APR activities eview of repacking 可编辑