2022年01PI028PICS对包装相关的GMP检查备忘

1、202201 PI 028-1 PIC/S 对包装相关的 GMP检查备忘PHARMACEUTICAL INSPECTION CONVENTIONPHARMACEUTICAL INSPECTION CO-OPERATION SCHEMEPI 028-113 January 2022AIDE-MEMOIREGMP INSPECTION RELATED TO PACKAGING包装相关的 GMP 检查? PIC/S January 2022Reproduction prohibited for commercial purposes. Reproduction for internal use is

2、 authorised,provided that the source is acknowledged.制止商业目的复制。仅供内部使用。TABLE OF CONTENTS 名目Document History 文件历史2Introduction 介绍2Purpose 目的2Scope 范围3Aide-Memoire 备忘4Revision History 变更历史8DOCUMENT HISTORY 文件历史Adoption by Committee由委员会承受31.10.2022Entry into force of PI 028-1PI 028-1 生效01.03.2022INTRODUC

3、TION 介绍The process of packaging of medicinal products is listed among the risk factors that may affect the quality of the finished medicinal products and may also cause mix-ups.药品的包装工艺列为可能会影响药品的质量的风险因子，并认为其可能导致药品混淆。The increased number of the defects of medicinal products occurred due to deficiencie

4、s in the process of labelling and packaging has drawn inspectors attention towards the need for identifying and clarifying the critical aspects of this specific stage of inspection, in order to have a uniform interpretation of the provisions of the current GMP guide concerning packaging of medicinal

5、 products and prevention of mix-up.越来越多的发生在标签和包装工艺中的缺陷导致的的药品缺陷已经引起来检查官的留意，他们认为需要对这个特定的步骤的检查的关键点进展识别和说明， 从而对现行 GMP 指南关于药品包装的条款进展统一解释，并防止药品混淆。In the light of technological progress, considering the wide variety of medicinal products developed, the 2022 PIC/S Seminar (Bucharest, Romania) was dedicated

6、to the GMP inspection of the final stage of manufacturing process (primary and secondary packaging, labelling.)由于科技进步，考虑到现在已有各种不同研发的药品，PIC/S 的 2022 年研讨会布加勒斯特，罗马尼亚专题争辩了生产工艺的最终步骤内包装、外包装和标签的 GMP 检查问题。This Aide-Memoire is the outcome from the 2022 PIC/S Seminar.本备忘是 2022 年PIC/S 研讨会的结果。PURPOSE 目的The purp

7、ose of this document is to provide guidance for GMP inspectors in preparation for inspections. This document aims to define the minimal requirements acceptable for an inspector as well as the requirements that provide maximum safety for the finished product (“best practices”).本文件的目的是为 GMP 检查官在预备检查是供

8、给指南。本文件目的是制订检查官可以承受的最低要求，以及为药品供给最大安全的要求最优标准。The Aide-Memoire is the direct result of the 2022 PIC/S Seminar. The Aide-Memoire should enable the inspector to assess the GMP compliance of the packaging process using the quality risk management tools.本备忘是 2022 年PIC/S 研讨会的直接结果。备忘使得检查官可以承受质量风险治理的工具对包装工艺的

9、 GMP 符合性进展评估。SCOPE 范围The following Aide-Memoire describes different areas which could be evaluated during the GMP inspection of packaging and labelling process. However, the Aide-Memoire should be considered as a non-exhaustive list of areas to be looked at during an inspection.以下备忘描述了在对包装和标签工艺进展GMP

10、 检查期间可以进展评估的不同区域。但是，备忘只能是作为一个未全尽的清单来使用。At the time of issue, this document reflected the current state of the art. It is not intended to be a barrier to technical innovation or the pursuit of excellence. The advice in this Aide-Memoire is not mandatory for industry. However, industry should consider

11、 PIC/S recommendations andAide-Memoires as appropriate.在签发本文件时，该文件反映的当前的抱负状态。本文件无意阻碍技术革或追求卓越。本备忘中的建议对制药行业来说并不是必需实施的。但是，制药行业应在适当时考虑 PIC/S 和备忘中的建议。AIDE MEMOIRE 备忘Area ofoperation/ Items 操作区域/工程Notes 留意点Crucial questions Supporting 关键问题Documents 支持性文件Area ofoperation/ Items 操作区域/工程Notes 留意点Crucial ques

12、tions Supporting 关键问题Documents 支持性文件Packaging Materials 包装材料Quality and purchasing fromWhat is theGMP GuidePurchasing质量和选购approved suppliers;是否从批准的供给商处选购auditing the manufacturing sites of suppliers of primary packaging materials for sterile products (vials,policy for suppliers approval?批准供给商的方针是什么？

13、Show me the audit report1.2 iv, 1.3vii,viii, 5.40,5.41, 4.2,4.11Ph.Eurrubber stoppers, syringes, 给我看一下审计etc.) and of printed报告materials;检查无菌产品内包材瓶、橡皮塞、等和印刷包材的供给商的生产地compliance with specifications;符合质量标准up-dating the documents (quality specifications), in accordance with the marketing authorization a

14、nd any subsequentDo the primary materials specifications comply with the Pharmacopoeia l parameters and limits?内包装质量标准是否符合药典工程和标准？Area ofoperation/ Items 操作区域/工程Notes 留意点Crucial questions Supporting 关键问题Documents 支持性文件variations;文件质量标准更，与上市批准和之后的变更全都delivery from supplier made such as to preserve th

15、e quality (to prevent contamination).从供给商处运送到厂过程中对质量的保管免受污染Receipt接收quality documents: certificates of analysis;质量文件：分析报告checking the conditions for packages shipment and handling;对包装发运和处理条件的检查integrity checks and identification of each batch of primary packaging material orShow me the records and S

16、OPs which apply when receiving primary packaging materials or printed materials给我看一下内包材或印刷包材接收时所用的记录GMP Guide5.27, 5.4,5.3,5.42, 5.434.19, 4.20,421printed material received;和 SOP每批内包材或印刷包材接收 DescribeinternalArea ofoperation/ Items 操作区域/工程Notes 留意点Crucial questions Supporting 关键问题Documents 支持性文件时的鉴别和

17、完整性检查de-dusting and cleaning of packages on the outside外包装除尘和清洁labelling system描述内部标识系统Storageadequate capacity, orderShow me theGMP Guideareasand organization, locationseasonal/annua 3.1 3.4,存贮区域plan available;存贮区域足够物料存贮，有序有组织放置，应有分区存贮图the cleaning status, procedure and records;清洁状态、清洁程序和记录physical

18、ly separated areas for “quarantine”, “approved”, “rejected/recalled” materials or a system that provides similar safety;“待检”、“放行”、“拒l trends and results of temperature and humidity monitoring给我看一下各季节/年度温湿度监控结果和趋势Show me the location plan and records5.5,5.7, 5.28,5.29, 3.18 3.23, 3.25收/召回”物料物理隔离区， co

19、ncerning或可以供给等同安全保障的隔离系统secured conditionsthese activities给我看一下分区存贮图和这些活Area ofoperation/ Items 操作区域/工程Notes 留意点Crucial questions Supporting 关键问题Documents 支持性文件(physically separated areas, controlled, authorized access) for storage of primary and secondary printed materials (cartons, labels, leaflet

20、s);内包材和外包装印刷包材纸箱、标签、说明书安保条件物理分别区域、把握、授权进入storage of one batch per pallet when the number of recipients allows -, without mixing batches on the same pallet ;每批存放于一个托盘-假设所接收的数量允许-同一托盘不允许混批存放storage conditions adequate to each category of materials (qualification of the ventilation, air conditioning un

21、it, critical parameters monitoring 动的相关的记录Area ofoperation/ Items 操作区域/工程Notes 留意点Crucial questions Supporting 关键问题Documents 支持性文件temperature, humidity);满足各类物料要求的存贮条 件通风系统确认、空调单元、关键参数监控温度、湿度existence of an efficient system to prevent entrance of rodents, insects or other animals;存在有效的系统以防止虫鼠、昆虫或其它动物

22、进入adequate control over destruction of materials.对物料销毁有充分把握Qualitysampling plan and conditions,Show me the GMPcontrol质量把握according to the material being sampled;sampling plan Guide and recordsAnnex取样打算和取样条件，依据物料不同specific laboratory equipmentfor the testing of packaging materials;for primarypackagin

23、g materials (including labels)8:1, 5,3.40, 3.41,6.1, 6.6,6.17, 5.54,Annex特定的对包材检验的试验室检测设备给我看一下内包 1: 91材包括标签 的取样打算和testing of packaging materials/packages in accordance with the methodology approved in the marketing authorization (functionality tests according to the manufacturer specification and te

24、sts according to current edition of relevant pharmacopoeia);包材/包装检测与批准的上市许可方法全都依据生产商质量标准进展的性能测试，以及依据相关记录Show me the approved specification and current results from internal testing给我看一下批准的质量标准和最近的内部检测结果的药典现行版本进展的测试 Show me thecertificatesintegrity testing for primaryissued by QCpackaging, differenti

25、ated forfor one or each category of finishedmore of these products (when applicable);materials内包装的完整性测试，不同品种制剂可能会不同适用时in-process controls with relevance for the quality of the primary packages used (weight, filling level, blister scan, leak test, verification of the printing of labels, bar code read

26、er challenges);对所用的内包装的质量进展的相关中控检查重量、充填水平、吸塑扫描、泄漏测试、印刷标签确实认、条形码可读性挑战测/packages used for primary packaging给我看一下由QC 给这些内包装所用的材料签发的报告试assessment of the integrity for a sterile product packaging.无菌产品包装的完整性评估Manufacturing designed and built-up toShow me theGMPpremises (packagingminimise the risk of conta

27、mination and mix-up- enough space, logicalqualificationGuide (IQ, OQ,PQ) Annex 1:of utilities used 5, 11, 12,area)生产设施包装区域positioning of packagingequipment, separation of each and every primary and secondary packaging line (different cleanliness levels);应为包装设备设计或建筑有足够的空间、物理区域，以inside theprimary pack

28、aging area给我看一下用于内包装区域里的公用系统确实认安装、运3.7, 3.8将污染和药品混淆的风险行和性能确认降至最低，对每个内包装和 Show me the外包装线进展分隔不同清洁水平qualification (IQ, OQ, PQ) of utilities (HVAC, PW, WFI, sterile steam, inertresults ofenvironmental monitoring (especially for primarygases used, if applicable);packaging of公用系统HVAC、纯化水、注射用水、无菌蒸汽、注入气体，适

29、用时确实认monitoring of environmental conditions based upon the nature ofsterile products)给我看一下环境监控的结果尤其是无菌产品的内包装the product (sterile or non-sterile).基于产品特性无菌或非无菌环境条件的监控How is the access ensured for products/ materials and personnel to production areas?生产区域如何把握产品、物料和人员进出？Area ofoperation/ Items 操作区域/工程No

30、tes 留意点Crucial questions关键问题Supporting Documents 支持性文件Packaging high performance,Show me the SOP3.343.39,equipment andprocess包装设备和工艺qualified and well-maintained;equipment, able to ensure the control during the primary/secondary packaging;高效、确认过的以及适当and records of the line clearance给我看一下包装线清洁的 SOP 和

31、记录Show me the checklist used for line clearanceAnnex 15-19,5.44-5.53,5.55, 5.57,5.38, 5.39维护的设备可以保证内 给我看一下包装线清包装/外包装过程中的把握保证line clearance (working洁所用的检查清单IQ, OQ, PQ and CQarea, packaging lines,安装、运行、性能确认label printing machinesShow me theand other equipments should be clean and free from any other p

32、roducts, materials or documents previously used);生产线清洁工作区域、包装线、标签印刷机和其它设备均应进展清洁，将其它产品、物料清理出该区域，去除之前所用的文件content of adequate level of details on the checklist for line clearance;检查生产线清洁的检查清单内容是否足够具体line cleaning;生产线清洁cleaning of dust extractors吸尘器的清洁checking of the type of label used and its attachme

33、nt on the primary package;检查所用的标签类型，以及内包材的附件qualification/validati on of the packaging equipment/process给我看一下包装设备/ 工艺的验证/确认Show me the calibration and maintenance records for the packaging line给我看一下包装线的校正和维护记录Show me the SOP and program for mix-up prevention给我看一下防止混淆的 SOP 和程序the presence of safety e

34、lements of the package (to prevent the counterfeit);包装安全因素的存在防伪validation of the packaging process (critical process operation) protocol, report and records;包装工艺的验证关键工艺操作方案、报告和记录adequate functioning of electronic devices to establish identity, such as barcode or RFID readers.识别用电子设备运行良好，例如条码或 RFID 读

35、码器waste handling废物处理Documentsbatch packaging records(BPR) on paper or electronic form (attention paid to level of access,How do you ensure the security of thedata entry in4.7 4.9,4.16,4.18,electronic signature, etc.) forthe electronic5.56,every batch or sub-batch5.15,manufactured;BPR?5.39所生产的每个批次或每个

36、子批 你们怎么来保证次的批包装记录BPR-纸质或电子形式要留意进入许可水平，电子签名等电子批包装记录的数据输入的安全性？SOPs and instructions forShow me thereconciliation, especially for the printed materials (including investigation of any discrepancy noticed and solving before batch release);records of investigation of any discrepancies noticed during reco

37、nciliation?物料衡算的 SOP 和指令，尤其 给我看一下在衡是印刷包材包括全部留意到的不平衡时的调查，以批放行前是否解决defined and adequate action limits regarding reconciliation;物料衡算指定的标准和充分的行动限adequate control of return in storage area of excess packaging materials;包材返回存贮区域的充分把握adequate and documented investigation of packaging process deviations.对包装

38、过程偏差进展充分调查算过程中觉察有不平衡的状况的调查记录How did you investigate the packaging process deviations?你们如何对包装工艺偏差进展调查？Show me the SOP for handling the obsolete or damaged printed并有记录packages给我看一下关于废弃或损坏的印刷包材的处理 SOPDocumentsbatch packaging records(BPR) on paper or electronic form (attentionpaid to level of access,How

39、 do you ensure the security of thedata entry in4.7 4.9,4.16,4.18,electronic signature, etc.) forthe electronic5.56,every batch or sub-batchBPR?5.15,manufactured;所生产的每个批次或每个子批次的批包装记录BPR-纸质或电子形式要留意进入许可水平，电子签名等SOPs and instructions for reconciliation, especially for the printed materials (including inv

40、estigation of any discrepancy noticed and solving before batch release);物料衡算的 SOP 和指令，尤其是印刷包材包括全部留意到的不平衡时的调查，以批放行前是否解决defined and adequate action limits regarding reconciliation;你们怎么来保证 5.39电子批包装记录的数据输入的安全性？Show me the records of investigation of any discrepancies noticed during reconciliation?给我看一下

41、在衡算过程中觉察有不平衡的状况的调查记录How did you investigate the packaging process物料衡算指定的标准和充分的行动限adequate control of return in storage area of excess packaging materials;包材返回存贮区域的充分把握adequate and documented investigation of packaging process deviations.对包装过程偏差进展充分调查并有记录deviations?你们如何对包装工艺偏差进展调查？Show me the SOP for

42、 handling the obsolete or damaged printed packages给我看一下关于废弃或损坏的印刷包材的处理 SOPPersonneladequate in terms ofShow me the 2.1, 2.2,人员qualification and training regarding hygiene practices, clothing and operation onparticular packaging equipments;关于卫生操作、更衣和操作，特别是包装设备的操作确认和培训应充分knows and applies the procedures regarding the activity performed;了解并实施相关操作程序performs operation reliably and with no impact on therecords of medica