TABLE OF CONTENTS目录 1. Document History 文件历史 2. Introduction 介绍 3. Purpose 目的 4. Scope 范围 5. Aide-Memoire 备忘 6. Revision History 修订历史 1. DOCUMENT HISTORY 文件历史 Adoption by Committee 被委员会采用 Entry into force of PI 030-1 实施
2. INTRODUCTION 介绍
2.1 The adoption of ICH Q7 as the first truly harmonised GMP guideline for active pharmaceutical ingredients (APIs) and the associated development of regulatory frameworks to implement the guideline as a regulatory standard mark the beginning of a new era of regulation for medicines.
采用ICH Q7作为真正意义上的原料药统一GMP指南，并伴随着法规框架的发展以实施指南作为法规的标准，标志着药品法规的一个新纪元。
2.2 The adoption of ICH Q7 by PIC/S occurred in May 2001 with the current version of the guideline having been available since 1 September 2007 as GMP PE 009 (Part II).
01.03.2009 12.11.2009 2001年5月PIC/S采用了ICH Q7，现行版本指南GMP PE 009(第二部分)在2007年9月1日公布.
2.3 The primary objective for implementing ICH Q7 is the reduction of the risks associated with the manufacturing quality of APIs and this cannot be achieved without an effective inspection system which addresses the specific aspects of the global API industry.
实施ICH Q7的基本目标是减少原料药生产质量所伴随的风险，要达到这个目标，必须制订有效的检查体系，以说明全球原料药行业的各个独特方面。
3. PURPOSE 目的
3.1 It is recognised that due to their background and experience the majority of GMP inspectors are more familiar with the inspection of finished products.
大家已认识到鉴于GMP检查人员的背景和经验，大部分检查人员对制剂检查更为熟悉。 Therefore, to assist inspectors not specialised in the inspection of API manufacturers this document has been developed to provide training and guidance for the preparation and performance of such inspections.
因此，为帮助非原料药生产商专门检查人员，制订本文，以给这样的检查准备和实施过程提供培训和指南。
3.2 This Aide-Memoire should also contribute to a harmonised approach for inspections of API manufacturers between the different PIC/S Members. 本备忘同时也对PIC/S不同成员之间对原料药生产商检查方法进行协调统一。
4. SCOPE 范围
4.1 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. 本文件代表签发时所能达到的最高水平，并无意成为技术革新或追求卓越的障碍。
4.2 This Aide-Memoire focuses on the preparation for inspections and chapters and/or sections of GMP PE 009 (Part II) which are specific to the inspection of API manufacturers or critical for the quality of APIs. For sections which include requirements similar to those in GMP Guide Part I devoted to Finished Products such as personnel, documentation, etc., please refer directly to GMP PE 009 (Part II). 本备忘主要内容是关于检查的准备，和GMP PE 009(第二部分)的各章节和/或部分的准备，针对的是原料药生产商的检查或原料药质量的关键点。对于与GMP指南第一部分制剂相似的要求，例如人员、文件等，请直接参考GMP PE 009(第二部分)。 5. AIDE MEMOIRE 备忘 1. Preparation of API inspection 原料药检查准备 Inspection Element Workflow 工作流程 Supporting documents 支持性文件 检查要素 Review the reports of any recent Inspection reports Inspection history inspections carried out and the outcome 审核所有最近的检查报告及检查结果 If appropriate, contact the 检查报告 检查历史 inspectorate that conducted the last inspection to verify the information 适当时，联系前次检查人员确认相关信息 Basic information Determine the number of different APIs Products related to the produced at the site 检查在该场所生产的原料药品种 Review(s) (PQR) 产品质量回顾PQR Quality APIs 与原料药有关的基本信息 Determine the classification of the APIs (antibiotics, hormones, cytostatics etc.) 检查原料药的类别（抗生素、激素、细胞抑制剂等） Determine the intended use of the APIs (topic, oral, injectable, inhalation, etc.) 检查原料药的用途（局部、口服、注射、吸入等） For each API, establish; -grade (freeze dried, micronised, sterile, etc.); -batch size; and - number of batches produced per year 对每种原料药， --级别（冻干、微粉、无菌等） --批量，及 --每年生产的批次数量 Basic information Determine if the facilities are Site Master File related to the site multipurpose or dedicated 与工厂相关的基本信息 检查设施是多产品共用还是专用 工厂主文件 If APIs are potent or highly toxic determine the containment measures Review a list of manufacturing equipment 检查生产设备清单 Review a list of SOPs 检查SOP清单 Review the flow of personnel and materials through finishing areas 检查成品区域人流图和物流图 If manufacturing operations, products SMF or services, are outsourced establish the name and address of the subcontractors 如果生产操作、生产或服务有外包，获取外包服务机构的名称和地址 工厂主文件 Basic information Review: related processes -Process flow charts; 与工艺有关的基本信息 -Detailed description of the process; -Stability studies results; -Impurity profile; -API starting materials definition etc. 检查 --原料药质量标准和检验方法 --工艺流程 --详细工艺描述 --稳定性试验结果 --杂质谱 to -API specifications and test methods; Pharmacopoeia; CEP; ASMF (previously DMF), CTD part 3.2; Batch Manufacturing Record if appropriate 药典、EP、ASMF（之前的的DMF）、CTD第3.2部分、批生产记录（适用时） --原料药起始物料定义等 If appropriate, contact assessors of the dossiers 适用时，联系文档的评估人员 Review validation status 检查验证状态 Validation Master Plan; list of activities scheduled 验证主计划，计划活动的清单 Changes 变更 Review recent major changes (new product, equipment, building renovation or extension etc.) 检查最近的主要变更（新产品、设备、建筑、改造或扩建等） Review scheduled major changes 检查计划的主要变更
2. Quality Management System 质量管理体系 Area of operations / items 操作区域/项目 Internal Approved and documented Are internal audits being Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 audits (Self schedule, which covers performed as scheduled? Can 2.40 inspections) all GMP activities they be substituted by third 2. Quality Management System 质量管理体系 Area of operations / items 操作区域/项目 内审 available 批准并记录的内审计划，应包括所有GMP活动 party audits? How is the frequency of internal audits determined? 内审是否按计划进行？是否由第三方审计？内审的频次如何决定？ Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 Composition of the team Is the composition of the appropriate 内审小组人员适当 audit team determined according to an SOP? Has consideration been given to: -Conflict of interest -Code of conduct -Qualifications -Independence from the area being audited (e.g. Who inspects the QA function) 审计小组是否根据SOP组成？是否考虑以下 --利益冲突 --实施要求 --资质 2. Quality Management System 质量管理体系 Area of operations / items 操作区域/项目 --独立于被审计区域（例如谁审计QA功能） Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 Qualification of any How is the suitability of 2.40, 3.30 external auditors 外部审计员资质 external auditors assessed? 外审员的适用性如何评估？ How does the company ensure 2.41 that corrective actions are effective and are completed in a timely manner? How do they check the effectiveness of preventive actions? 公司如何保证纠正措施有效，并及进完成？如何检查预防措施的有效性？ 计划完成后的确认 Effectiveness of the system to plan the corrective and preventive actions Verification of the completion of an action 系统制订纠正和预防措施的有效性 The flow of information How is the responsible is effective 信息流有效 management informed about the results of the audits? 如何将审计结果通知有关管理层？ 2.41, 2.18 Product Quality Regular PQRs performed Is the data evaluated for the 2.50, 2.51 in a timely manner (e.g. presence of trends, and are Review (PQR) within three months from these acted upon? Are 2. Quality Management System 质量管理体系 Area of operations / items 操作区域/项目 年度产品回顾 the end of the period being evaluated). Data from in-process complaint, out-of-specification (OOS) and deviation Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 controls, batch release investigations, reported, analysis and other key quality indicators e included 适当的方式定期进行年度产品回顾（例如，时间周期considered and evaluated in the PQRs? Are the PQR results used to re-evaluate the expected monitoring ranges in Batch Manufacturing Records? 结束前3个月进行评估）。数据是否评估趋势，是否对趋势应包括中控数据、产品放行采取行动？客诉、OOS和偏差调分析和其它关键质量指标。 查在PQR中是否报告、考虑和评估？PQR结果是否用于对批生产记录中的监控范围进行再评估？ A review of OOS, critical Are required changes IPC and API test results, highlighted in the PQRs deviations, complaints, implemented through the returns and recalls, non change control system? conformances and related investigations, including the PQR中强调的所要求的变更是否通过变更控制系统实施？ 2.5, 6.61, 6.72, 8.36, 11.15 effectiveness of the corrective preventive and actions 2. Quality Management System 质量管理体系 Area of operations / items 操作区域/项目 conducted A review of changes conducted Stability program data verified 对OOS、关键中控和原料药检查结果、偏差、客诉、退货和召回、不符合及相关的调查，包括纠正与预防措施的有效性评估的回顾。 对已实施的变更的回顾 稳定性数据的确认 Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 Based upon the review, the validation status of a manufacturing process is evaluated and recorded 基于审核，生产工艺的验证状态应进行评估和记录 2.5, 12.60 Complaints 客诉 All quality related How are complaints reported, 15.10 complaints recorded and including orally, recorded investigated according and investigated? 2. Quality Management System 质量管理体系 Area of operations / items 操作区域/项目 to a written procedure 所有质量相关客诉应根据书面程序进行记录和调查 客诉如何记录，包括口头、书面记录和调查？ Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 Complaint records Is the nature of the complaint 15.11 include all relevant correctly reported – i.e. is details (date and source it possible to establish if of the complaint, nature there is a recurring problem? of the complaint, to batch 客诉的特性是否正确报告---即如果是一个反复发生的问题，是否可能识别 references number and production date) 客诉记录包括所有相关细节（客诉日期和来源、客诉属性、相关的批号和生产日期） The complaint investigation report identifies corrective actions and follow up/preventive actions 客诉调查报告制订纠正措施、跟踪/预防措施 Has the impact of this complaint on other batches been considered? 是否考虑到该客诉对其它批次的影响？ 15.11 The final report Does the corrective action 15.11 2. Quality Management System 质量管理体系 Area of operations / items 操作区域/项目 specifies the kind of correctly address the response provided to the problem, or it is focused on originator complaint of and the “customer satisfaction”? the (i.e. the company looked for Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 decision on the status of the root cause of the problem, the product 最终报告批出需要向投诉者给出的回复类型，产品状态的决定 or simply “reimbursed” the originator of the complaint?) Was source of the complaint removed in an effective manner through preventive actions? 纠正措施是否正确改正了问题，或者其是否关注“客户满意”？（即公司找到问题的根本原因，还是简单敷衍投诉人？）通过预防措施是否有效消除客诉原因？ Complaint records and Are complaints correctly 13.12-13, 15.12 reports are evaluated in evaluated in PQRs? (i.e. is the PQRs in order to there any evaluation of identify trends, product reoccurrence and trends?) Are related frequencies, and corrective/preventive severity 客诉记录和报告在年报中actions managed through the change control system? 2. Quality Management System 质量管理体系 Area of operations / items 操作区域/项目 进行评估，以便分析其趋客诉在年报中是否正确评估？Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 势、产品相关频次和严重性 （即是否对再次发生和趋势进行分析） 纠正预防措施是否通过变更控制系统进行管理？ Recalls 召回 The “recalls SOP” Is the recall process clearly 15.13, 15.14 specifies the threshold documented and easy to (by way of example cases, follow? or other means) for which a recall shall be considered The “recalls SOP” specifies who can initiate a recall, and how the recall process shall be managed. (i.e. who is to be informed, and how recalled goods are to be treated and stored) 召回SOP应说明在什么情况下考虑召回（列举样例，或其它方式）。召回SOP应说明谁启动召回，如何管理召回流程（即要通知谁，如是否清楚写明召回过程，易于执行？ 2. Quality Management System 质量管理体系 Area of operations / items 操作区域/项目 何召回产品，如何处理和存贮） Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 The recall procedure Is there a requirement to 15.15 clearly defines how to inform the authorities, and inform the regulatory request cooperation (in terms authorities in the case of advices and/or actions), of recall related to a in cases where the recall is serious problem 召回程序应清楚定义当召related to a potentially life-threatening situation? 回与一个严重问题相关时，如果召回与潜在生命威胁情况如何通知药监当局 相关，是否要求通知药监当局，要求合作（例如建议和/或措施）
3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 4. Building and facilities 厂房和设施 3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 Area of operations / items 操作区域/项目 General 一般 Product protection increases from early through to final manufacturing steps 对产品的保护应随着生产步骤的推后而增加 Notes 注意点 Crucial me questions/Show Supporting documents 支持性文件 关键问题/给我看 Have procedures been implemented to protect the API from contamination during the final stages of manufacture? (e.g. sieving, milling and packaging) 是否实施程序以保证原料药在生产的最终阶段不受污染？（例如过筛、磨粉和包装） 4.10 The level of product Have procedures been protection is dependent implemented to protect the upon the product type and API when exposed to each the expected time of stage of the manufacturing exposure environment 对产品保护的要求依据于产品类型，和暴露于环境的to the environment (sampling, loading, unloading, etc.)? 是否实施程序以在各生产阶段暴露于环境中时对原料药4.10 3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 时间 进行？（取样、装卸料等） What are the additional 4.10 controls? 额外控制有哪些？ APIs with microbiological specifications require additional controls 有微生物质量标准的原料药需要额外控制 Have controls been implemented to ensure that the activities in surrounding areas/ neighbourhood are not an actual source of contamination? 是否有进行控制以保证在周边区域/邻近区域的活动不是实际的污染源？ SMF Have controls been implemented to ensure that highly toxic non pharmaceutical materials (herbicides, pesticides, etc.) are not manufactured in the same building/equipment as 4.43 3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 used for APIs. 是否有进行控制以保证高毒性非药用物质（除草剂、杀虫剂等）不与原料药使用相同的建筑/设备？ APIs specific areas / activities 原料药指定区域/活动 Tank farms 贮罐区 Are the general condition of tanks and ancillary equipment (pumps, pipes, vents, etc.) appropriate for their intended use? Are all tanks and associated pipes appropriately labelled and secure? 贮罐和辅助设备（泵、管道、通风设施等）是否有一个通用条件要求，适用于其用途？是否所有贮罐和相连接的管道适当标签和保护？ 7.21, 7.22 Solvent recovery plant 溶剂回收车间 See recovery chapter 参见回收章节 Are washing areas Washing rooms 4.10, 4.11 3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 清洁间 appropriately managed and controlled?(equipment flow, storage of dirty and clean equipment, labelling) 清洁区域是否适当管理和控制？（设备流程、脏的和清洁设备的存贮、标识） Control rooms 控制间 Have computerised systems been validated? Have the backup systems been verified? Are procedures in place for the analysis of data? 所用的计算机系统是否验证？备用系统是否确认？是有否数据分析程序？ 5.4 Compressed air / nitrogen / other utilities 压缩空气/氮气/其它公用系统 PIC/S Aide-Memoire on Utilities (PI 009) PIC/S对公用系统的备忘3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 （PI009） Sewage and refuse 三废 Is waste effectively removed from production areas (e.g. using closed systems like containers or plastic bags to prevent contamination of other areas)? 废话是否从生产区域有效移除（例如采用封闭系统如容器或塑料袋，以防止其对其它区域造成污染）？ 4.60 Are all waste disposal systems correctly identified? 是否对所有废物处理系统进行正确识别？ 4.60 HVAC 空调净化系统 Does the HVAC system 4.21, 4.22 provide an appropriate finishing are environment for areas where APIs exposed? 空调净化系统是否为原料药3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 暴露区域提供适当的环境？ Water 水 Drinking (potable) water Are records of CoA acceptable if suitable for available? Has testing at an intended use 饮用水可用于适当的用途 appropriate frequency been conducted? Does potable water meet at the minimum WHO guidelines (e.g. free from chemicals such as carcinogens, toxic substances, metals, organochlorine pesticides, lindane, DDT, organic compounds, etc; radiologicals and micro-organisms) 检验报告记录是否可提供？检验频次是否恰当？自来水是否符合WHO最低要求指南（例如无致癌、有毒化学物质，金属、有机氯杀虫剂、林丹、DDT、有机化合物等；辐射物和微生物） WHO饮用水质量指南 4.30, PIC/S Aide-Memoire on Utilities (PI 009) WHO 4.31, Guidelines for drinking-water quality 参见PIC/S关于公用系统的备忘（PI009） 3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 4.33 If water sourced from river, wells, etc. and treated by the manufacturer, has the treatment process been validated? Have the affects of seasonal variation and human activity on the water quality been addressed? Is the process monitored? 如果水源为河、井等，由生产商处理，处理流程是否经过验证？季节性变化和人类活动对水质量产生的影响是否有说明？对工艺是否进行监控？ Non-sterile API intended Is the water used in the final to be used in a sterile drug isolation and purification 用于无菌产品的非无菌原料药 steps monitored and controlled for microbial counts, objectionable organisms and endotoxins? 用于最后分离和精制步骤的水是否进行微生物限度和阳4.34 3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 性菌、细菌内毒素监控 Design 设计 Defined areas or other control system for different activities (storage, sampling, quarantine, production, etc.) 对不同活动定义区域或其它控制系统（存贮、取样、待检、生产等） 4.14, SMF Potential contamination and cross-contamination has been prevented by the location and placement of equipment 在布局和设备定位理防止潜在污染和交叉污染 4.11 Flow of Are the flow of materials and personnel appropriate for the processes? Are appropriate indications displayed in critical areas (gowning 4.13 materials and personnel 物流和人流 3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 instructions, labelling for clean/unclean areas, incoming/outcoming materials, etc.) 物流和人流是否与工艺适合？关键区域是否恰当标示（更衣指令、洁净区/非洁净区标识、进入/出去物料等） Containment 限制 Design of the multipurpose use containment area 多功能使用的限制区域设计 Has the containment area been qualified for multipurpose use? 限制区域作为多功能区域是否经过确认？ If HVAC is not dedicated, what controls are in place to prevent cross-contamination? 如果空调净化系统不是专用，采用什么方式预防交叉污染？ 4.22 3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 in 4.40 4.41 Penicillins and cephalosporins Other highly sensitizing, toxic, potent materials 青霉素和头孢类产品、其它高致敏性、毒性、高效价物料 Are they produced dedicated areas? Are sensitizing, toxic and potent materials either produced in dedicated areas or are validated inactivation and/or cleaning procedures established and maintained. 是否在专用区域内生产？致敏性、毒性、高效价物料在专用区域内生产，或灭活和/或清洁程序已建立并经过验证，并进行维护 Controls to prevent Have procedures to prevent 4.42 cross-contamination established? performance procedures monitored? exhibiting behaviour gowning prevent Are Is of been the these being staffs cross-contamination 防止交叉污染控制 appropriate and personal to techniques cross 3. Personnel 人员 Area of Crucial questions/Show Supporting operations / items 操作区域/项目 Notes 注意点 me 关键问题/给我看 documents 支持性文件 Cf. Scope 4.2 参考范围4.2 contamination? 是否建立防止交叉污染的程序？这些程序的效果是否有监控？员工行为和更衣要求是否能防止交叉污染？ Are measures in place to ensure that cross-contamination from equipment, materials and personnel moving from one dedicated area to another area is avoided? 是否有措施来保证避免设备、物料和人员从一个专用区域到另一个专用区域移动时所带来的交叉污染？ 4.42 5. Process equipment 工艺设备 Area of operations / items Notes 注意点 关键问题/给我看 Supporting documents 支持性文件 Crucial questions/Show me 操作区域/项目 This section is to be developed at the next revision of the Aide-Memoire 本部分将在下一版本备忘中加入 5. 6. Documentation and records 文件和记录 Area of operations / items 操作区域/项目 Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 Cf. Scope 4.2 参见范围4.2 7. Materials management 物料管理 Area of operations / items 操作区域/项目 Suppliers 供应商 Critical materials and Have supplier control their suppliers 关键物料及其供应商 procedures been defined and implemented? 是否制订关实施供应商控制程序？ Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 7.11 Supplier evaluation Have the following been considered in supplier 7.31 供应商评估 control procedures? -a review of the history of supplier -completion of a questionnaire by the supplier including information about quality system, quality certifications, third party audits, site master file etc… -a supplier audit including QC labs (considered for critical materials) -evaluation of samples (for new suppliers) 以下内容在制订供应商管理程序时是否考虑？ --检查供应商历史 --由供应商填写包括质量体系、质量证书、第三方审计、工厂主文件等信息的问卷 --对供应商进行审计，包括对QC化验室（对关键物料应考虑） --对样品进行评估（新供应商） Approved suppliers list Does the list include the 7.12, 7.13 7.20 批准的供应商名单 name and address of the manufacturer (not only trader)? Is it an updated and controlled document? Is it available for people in charge of receiving goods? 清单是否包括生产商（不仅仅是贸易商）的名称和地址？文件是否更新和受控？接收物料的人员是否可以获得？ Starting material from animal origin with TSE risk 具有TSE风险的动物来源起始物料 Additional records 附加记录 -Origin of raw materials: National country, supply chain, veterinary inspection / certificates, age of animals -Type of tissue used, collection method, risk of cross contamination during the collection -Manufacturing process: overview of the process, reduction of the TSE risk (validation), risk of cross contamination, cleaning validation -Traceability: supply chain, availability of the information back to the slaughterhouses / or international guidance documents (e.g. EP general monograph 5.2.8) animals --原料来源：国家、供应链、兽药检查/证书、动物年龄 --所用组织类型，采集方法，采集过程中交叉污染的风险 --生产工艺：工艺概览、降低TSE风险（验证）、交叉污染风险、清洁验证 --可追踪性：供应链、可追踪至屠宰场所/动物 Change control Changes are effectively 变更控制 system used to manage managed through the change control system 通过变更控制系统对变更进行有效控制 变更控制系统是否也用于管理物料和供应商的变更？ What systems are in place 7.20 to ensure appropriate transport and storage changes to materials and suppliers? Is the Change Control 7.14, 13. Storage 存贮 Transportation and storage for raw materials, and intermediates requiring conditions have been special handling 有特殊要求的原料和中间体的运输和存贮 maintained? 采用什么体系保证对运输和存贮条件的适当维护？ Where status control of material is by physical location are the locations well marked? Is access to these locations restricted to designated personnel? 10.11, 7.20 5.40, Validated electronic systems for material status control are acceptable. In such cases, physical segregation may not be required 经过验证的物料状态控制电子系统是可以接受的。在这种情况下，物理隔离可能不需要。 Where status control of material is by electronic means, is access to the electronic system restricted to designated personnel? 如果物料状态控制采用物理方式，是否所有区域均进行了标识？进入这些区域是否仅限于受权的人员？如果物料状态由电子方式进行控制，进入电子系统的许可是否仅限于受权的人员？ Bulk materials Non dedicated tankers 散装物料 非专用槽车 Does the cleaning procedure, and certificate of cleaning, for non-dedicated tankers cover accessory parts, including transfer hoses? 非专用槽车的清洁程序和清洁证书是否包括了所有必要的部件，包括输送用软管？ 7.22 Note: Section 7.22 is applicable to reusable containers 注：7.22适用于重复使用的容器 If non dedicated reusable 7.22, 8.51 containers are used, is there evidence that they are properly cleaned? 如果容器重复使用，是否有证据证明进行了适当的清洁？ Are sampling plans appropriate for each type 7.33 Sampling 取样 Sampling plan 取样计划 of raw material being selected for testing? Does each sampling plan include a rationale for the selected method? 取样计划是否适用于每种原料类型？每个取样计划是否包括了选择方法的合理性论述？ Sampling environments appropriate for the Has consideration been given to the sampling 7.34 materials being sampled environment for each 取样环境是否与需要取的样品相适应？ material being sampled? Does the plan take into account the material type, its susceptibility to microbial contamination, its use in a particular manufacturing step and the final dosage form? 取样环境是否考虑所取样品的特性？取样计划是否考虑物料类型、受微生物污染的可能性、所用生产步骤的特殊性、原料药所用于制剂剂型？ Is each batch identity Analysis 分析 Identity testing 鉴别测试 tested? 7.30 每个批次是否进行鉴别测试？ Extent and frequency of If reduced testing 7.31 testing 检测的项目和频次 performed, how was the supplier approved? At what intervals is full testing conducted? 是否实施部分检测，供应商如何批准？多少频次进行全检？ 8. Production and in process controls 生产和中控 Area of operations / items 操作区域/项目 Notes 注意点 Crucial questions/Show me 关键问题/给我看 All the production Are production operations verified operations actually for compliance with performed in the production dedicated or 8. PIC/S Aide-Memoire 生产实际操作是在专用还是共用厂房中进行？ Are the critical in the ASMF or parameters recorded 生产操作和公用设施的一般考虑 module 3, part 3.2.1 of CTD or as described by ICH M4Q 关键参考是否记录和控制？ 所有生产操作应与GMP指南中6.2，6.3，Do formal procedures 6.4，6.5要求的生产文件一致，与ASMF中描述的生产工艺一describing the production process exist? PIC/S关于生物技术生产检查备忘（1.4） and controlled? manufactures (1.4) on the Inspection of Biotechnology Supporting documents 支持性文件 documents specified multipurpose in 6.2, 6.3, 6.4, General considerations 6.5 of the GMP on the production operations and on facilities Guide, and the process described facilities? 致，或与ICH M4Q或CTD模块3第3.2.1部分描述的工艺一致 是否有正式程序对生产工艺进行描述？ Do production operations correspond with the defined process? 生产操作是否与定义的工艺一致？ Is the facility monitored to ensure appropriate conditions are maintained? 是否对设施进行监控以保证维护适当的条件？ Has the method of monitoring been verified? 监控方法是否经过确认？ Is an appropriate level of protection given to centrifuges, filters, ovens, etc? 对离心机、过滤器、烘箱等是否有给予适当的保护？ Does the monitoring of the quality of water demonstrate that the specification has been met 对水质量的监控是否能保证其符合质量标准 Are the critical parameters trended? 关键参数是否有趋势？ Do the parameters stated in the registered file relate to the operations documented in the Batch Record? -Process parameters, Compliance to registered file and general consistency 与注册文件一致及一般性符合 -IPC, -Specifications for intermediates and finished product 以下参数是否在注册文件中说明 --工艺参数 --中控 --中间体和成品质量标准 Does the facility 注册文件 1.1 § 4 Registered file have the capability to manufacture the batch size of the APIs produced? 设施是否有能力生产出原料药的批量？ Is the inspected site’s address consistent with the registered file? 被检查的场所地址是否与注册场所一致？ Are all production areas declared in the registered file? 注册文件中是否指明所有生产区域？ Raw materials: Are dispensing areas Dispensing area Production Operations 生产操作 surfaces, equipment and environment 配料区和设备是否符合原料：配料区表面、设备和环境 其用途？ and equipment fit for purpose? 8.10, 6.52 Are containers suitable and appropriately labelled? Is material status controlled? 是否所有容器均适用并8.11 适当标签？物料状态是否受控？ Are all critical activities witnessed or Critical weighing activities independently confirmed and verified 关键称重活动进行单独确认 是否所有关键活动均有第二人复核或有等同的控制？生产人员是否在使用前复核物料正确？ Do production personnel verify that materials are correct prior to use? 8.12, 8.13 subject to equivalent controls? Yield within Have appropriate yield ranges been set? Is the batch yield within range? For critical process steps, are deviations in yield investigated? 是否设定了适当的收率范围？批收率是否在范围内？关键工艺步骤收率偏差是否进行了调查？ 8.14 expected range 收率在期望的范围内 Deviations documented investigated Are deviations and documented and explained? Has an 8.15 偏差记录和调查 investigation been performed for critical deviations and, if necessary, corrective actions implemented? 偏差是否记录和解释？关键偏差是否进行调查，必要时实施纠正措施？ For each major unit of 8.16 equipment is the Process indicated 工艺状态指示 status processing status identified? 对每个主要设备单元，工艺状态是否进行标识？ Reprocessing and Reworking appropriately controlled 返工和再加工应适当控制 What systems are in place to track materials for rework, or reprocessing, and to prevent unauthorised use? 跟踪再加工、返工物料，防止未授权使用的系统是怎样的？ 8.17, 14.3 14.2; Time Limits 时间限制 Time limits for Where time limits process operations, have been set, are and for the storage these being met? Are of intermediates deviations 8.20, 8.21 工艺操作、中间体存贮的时间限制 documented and evaluated? 如果有设定时间限制，是否符合该时间限度？偏差是否记录和评估？ In-process Sampling and Controls 中控取样和控制 Written Procedures Do written procedures 8.30 available for the monitoring and control of exist to monitor and control the production process? production process Are the procedures 生产工艺监控应有书面程序 based upon development / historical information? 是否有生产工艺监控的书面程序？程序是否基于研发/历史信息？ Acceptance Criteria Do the in-process appropriate to controls and 8.31 process step / stage acceptance criteria 工艺步骤相适应的可接受标准 become more stringent for the later processing steps? 中控和可接受标准在接近成品的工艺步骤是否更严格？ Critical in-process Has the Quality Unit 8.32 controls are documented and approved by the given approval for in-process controls? 质量部门对中控进行批Quality Unit 关键中控是否记录并由质量部门批准 准吗？ In-process controls Are qualified staffs 8.33 performed and documented by qualified staff 中控是否由有资质的员工实施并记录 performing in-process controls? Are adjustments made to processes in accordance with pre-established and validated limits? Are IPC results documented in the batch record? 中控是否由有资质的员工实施？对工艺的调整是否与预设定的和验证过的限度一致？中控结果是否在批记录中记录？ Are there written Sampling Procedures sampling procedures documented and scientifically sound 取样程序应记录并科学合理 which are scientifically sound? 书面的取样程序是否科学合理？ Are sampling procedures designed to prevent 8.34 In process sampling : Prevention of 8.35 contamination and assurance of the integrity of the sample contamination and ensure the integrity of the sample? 取样程序的设备是否可中控取样：防止污染、以防止污染并保证样品保证样品完整性 完整性？ Does the company blend batches and is Blending of batches Blending Batches of Intermediates or APIs 中间体或原料药混批 defined and controlled controlled? 对混批进行定义并使受控 公司是否有混批行为？混合工艺是否定义并受控？ this process defined and 8.40 Only meeting batches Have approved batches all input been 8.40 specifications may manufactured by the be blended 只有符合批准的质量标准的批次可以被混合 same process, been individually tested and specification? 所有用于混合的批准是否由相同的工艺生产、经过独立检测并符合质量标准？ meet Is the blended batch tested conformance specification? 混合批次是否经检测符for with 8.43 合质量标准？ Traceability of Is it possible to all the 8.44 material used in a identify blended batch 用于混合批次的物料的追踪性 input batches that make up the blended batch? 是否可能识别出所有用于混合的投料批次？ Validation of the Is the blending 8.45 homogeneity of the operation validated blended batch 混合批次的均一性验证 to show homogeneity of the combined batch where physical attributes of API’s are critical in the dosage form? 如果原料药的物理属性在制剂生产中很关键，混合操作均一性是否经过验证？ Impact of blending Does the blending process on product operation adversely stability 混合工艺对产品稳定性的影响 affect product stability? If so have further stability tests been performed. 混合操作对产品稳定性是否有不良影响？如果有，则需要进行稳定性试验。 8.46 Expiry / Retest date Is the expiry/retest determination 有效期/复验期决定 date of the blended batch based upon the expiry/retest date of the oldest batch in the blend? 混合批次的有效期/复验期是否根据用于混合投料批次的最早的批次的有效期/复验期制订？ 8.47 Contamination Control 污染控制 Prevention of contamination of batches by carry Is the carryover of degradants and microbial 8.45, 8.50, 8.51, 8.52 over from a previous contamination, that batch 防止前一批混入后一批导致的污染 could impact upon the established API impurity profile, prevented? Consider: -Frequency of inter batch cleaning. -Environmental controls 是否防止降解产物和微生物污染对原料药杂质谱造成影响？要考虑 --批间清洁的频次 --环境控制 9. Packaging and identification labeling of APIs and Intermediates 原料药和中间体包装和标识 Area of operations / items 操作区域/项目 Packaging and Impact labeling 包装识 和标of Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 packaging Do Packaging materials 9.21 alter the quality of the API or intermediate? 包材是否对原料药或中间体产品形成影响？ materials on product 包材对产品的影响 Representative label 代表性标签 Does the BMR include a 9.36 representative label? 批记录是否包括一张代表性标签？ Prevention of cross contamination if containers reused 如果使用了回用容器应防止交叉污染 Are there appropriate procedures to avoid mix-up and cross contamination? Consider: -cleaning -removal of labels 是否有适当的程序防止混淆和交叉污染？应考虑 --清洁 --去除旧标签 9.22 The issue of labels must Is there an effective 9.3 be controlled system for the issuing of 标签需要控制 labels? 标签签发是否有一个有效的系统？ If and API is transferred outside the control of the manufacturer is the name The labelling of an API and address of the must ensure traceability manufacturer incorporated and provided instruction into the label. If on any special transport required, are special or storage requirements storage conditions 一种原料药的标签必须保证可追踪性，如有特殊运输或存贮条件要求应在标签上提供指示 incorporated into the label. 如果有原料药运出生产商控制范围以外，生产商的名称和地址是否包括在标签中？必要时，特殊的存贮条件是否包括在标签中？ 9.43, 10.22 Effectiveness of the Has the sealing system been 9.46 sealing system 封签系统的有效性 validated? 封签系统是否经过验证？ 10. Storage and distribution 存贮和销售 Area of operations / items 操作区域/项目 Storage and Appropriate areas Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 storage Is there adequate space 4.11, 10.10 including specific areas distribution 存贮和销售 适当的存贮区域 for returned, rejected, quarantined materials? 以下各功能是否有充足的区域：退货、不合格品、待检物料？ Have the specified storage 10.10 conditions been fulfilled? 是否满足特定的存贮条件？ Are FEFO / FIFO rules met? 7.42 是否符合FEFO/FIFO要求？ Controls of transfers If quarantined material is 10.20 under quarantine 待检状态下的转移控制 to be transferred, are there effective controls and documentation in place to prevent use before formal release by the manufacturer? 如果待验物料需要进行转移，是否采取有效控制和记录以防止在生产商进行正式放行前使用？ Transport methods and Has the responsibility for conditions 运输方法和条件 the transport been assigned? Is the assignment appropriate? 是否赋予运输责任？该赋予是否恰当？ How are the specified 10.21 storage conditions maintained transport? during 在运输过程中如何维护指定的存贮条件？ Is the level of control over 10.23 the contractor for transportation adequate? Consider: -audits by the API manufacturer -agreements -questionnaire, etc. 运输分包商的控制水平是否充分？考虑 --原料药生产商的审计 --协议 --问卷，等 The traceability of Is there a system in place 10.24 materials and products for product recall? extends to the point of first supply 原料和产品延伸至第一供应点的的可追踪性 是否有产品召回体系？ 11. Laboratory controls 实验室控制 Area of operations / items 操作区域/项目 Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 See PIC/S Aide Memoire PI-023 参见PIC/S备忘PI-023 12. Validation 验证 Area of operations / items 操作区域/项目 Validation Policy 验证方针 Notes 注意点 关键问题/给我看 Crucial questions/Show me Supporting documents 支持性文件 Is the company's validation 12.10, 12.11 policy documented? 公司验证方针是否记录？ Are all critical manufacturing steps validated? 是否所有关键生产步骤均经过验证？ 12.12 Validation Documentation 验证文件 Validation protocol Is the validation protocol 12.20 with the established and approved compliant by the Quality Unit 拟定验证方案，由质量部门批准 company’s policy? validation 验证方案是否与公司验证方针一致？ Critical steps that require validation and acceptance criteria specified 说明需要验证的关键步骤和Has the rationale for identifying certain manufacturing steps and operating parameters as critical, been documented? 12.21 可接受标准 识别哪些生产步骤和操作参数是关键的合理性是否记录？ The validation approach What is the validation 12.10, 12.4 adopted defined and approach Consider : -prospective, concurrent, or retrospective -the number of process runs 采用了何种验证方法？考虑 --前验证、同步验证、回顾性验证 --验证轮次 adopted? documented 定义和记录所采用的验证方法 The results of validation Are variations from the 12.22, 12.23 must be documented Any protocol documented and identified deficiencies justified? evaluated and documented 验证结果必须记录。所有缺陷进行评估和记录 与方案不符合处是否记录和评估 Any corrective actions implemented documented 所有纠正均应实施和记录 and Qualification 确认 Qualification (DQ, IQ, OQ, Have all qualification PQ) conducted for critical activities been completed equipment and ancillary before process validation systems (both new and begins? existing), for intended 是否所有确认活动均在工艺12.30 process, as appropriate 关键设备和辅助系统（新的和已有的）应在适当时确认（DQ,IQ,OQ,PQ）其符合既定用途 Approach Process Validation 工艺验证方法 to All operations determined critical to the quality and purity of the API are to be validated 所有认为对原料药质量和纯度关键的操作均应进行验证 验证开始前完成？ 12.12, 12.40 If prospective validation has not been performed, has the validation approach taken been justified? 如果未采用前验证，则所采用的验证方法需要进行论述 12.41 Prospective Validation 前验证 Prospective validation 12.42, 12.50 consisting of at least three consecutive successful batches must have been completed before commercial distribution of the API 前验证至少包括三个连续成功批次 Concurrent Validation 同步验证 Where only a limited Are batches released for 12.43, 12.50 number of API batches are commercial distribution, manufactured, or where before manufacture completion of is concurrent validation, infrequent, concurrent subjected to a thorough validation of at least monitoring and testing three consecutive programme? 在同步验证完成之前放行用于商业销售的批次，是否经过完整的监控和检测程序？ successful batches is acceptable 如果仅生产少量原料药批次，或生产不频繁，可以接受连续至少三个成功批次进行同步验证。 Retrospective Validation 回顾性验证 The number of process runs Are batches selected for 12.45, 12.50 selected for retrospective validation of all retrospective validation representative should be sufficient to batches made during the demonstrate process review period? 回顾性验证所选择的批次是否代表回顾期间所有生产批次？ consistency. In general, data from ten to thirty consecutive batches should be examined Test results from retained samples can be tested to obtain data for retrospective validation 回顾性验证所用的批次应足够多，可以论证工艺的一致性。一般来说，需要检查十到三十连续批次。留样所得的检验结果可以用于回顾性验证所需数据检测。 Impurity Profile Process validation should confirm that the impurity profile of each API is 12.52 杂质谱 within the limits specified 工艺验证应确认所有原料药杂质谱在既定限度内 Periodic Review 周期回顾 There should be a periodic Are Product Quality Reviews 12.60, 2.5 review of systems and used to confirm that the processes with respect to process under review validation status 对系统和工艺应周期性进行验证状态的审核 remains validated? 产品质量回顾是否用于确认工艺仍保持在验证有效状态？ Cleaning validation 清洁验证 Focus: multi and purpose Are cleaning procedure final validated? If not, is there any justification? Is facilities manufacturing steps 焦点：多功能设施和成品生产步骤 cleaning validation directed to situations that poses the greatest risk? 清洁程序是否经过验证？如果没有，是否有论证？清洁验证所选的条件是否代表最大风险？ Rational behind the use of Are documents available either validated or non regarding risk assessment validated cleaning which consider: -characteristics of contaminants (e.g. toxicity, solubility, potency and stability) -equipment (product contact material and methods for equipment used at different stages of production 用于不同步骤的生产设备所使用的清洁方法是否需要验证应有合理性 relative surface area, places difficult to clean) -process flow (purification steps, bulk size, product change over) -at the minimum, selection of product(s) which represent(s) the worst case scenario (product change-over, maximum acceptable residue limit, etc.) 是否有关于以下风险的评估文件 --污染物特性（例如毒性、溶解性、效价和稳定性） --设备（产品直接接触物料和相对表面、难清洁位置） --工艺流程（精制步骤、批量、产品更换） --最低要求，选择代表最差情况（产品更换、最小可接受残留限度等）的产品 Cleaning procedures are to Are the cleaning procedures 12.71 be validated 清洁程序需要进行验证 routinely used in production the same as those used in the validation studies? Are the cleaning methods applied in production the same methods as those used in the validation studies? Is cleaning routinely performed after the manufacture of the same number of batches? 用于日常生产中的清洁程序是否与用于验证研究的清洁程序相同？用于生产的清洁方法是否与用于验证研究的清洁方法相同？日常生产是否在经过相同批次后进行清洁？ Sampling methods involving rinse/swab, with an acceptable recovery, validated (including sampling for microbiological assessment) 取样方法涉及淋洗/擦拭，应具有可接受的回收率，经过验证（包括取样方法的微生物评估） Are personnel performing sampling properly trained and assessed? Is the sampling method used to monitor cleaning procedures the same method used in the validation studies? 取样人员是否适当培训和评估？用于监控清洁程序的取样方法是否与验证研究中所用的相同？ 12.73 12.76 Analytical test methods Is the analytical test appropriately validated 分析方法应经过适当验证 method sufficiently sensitive related to the established residue limits? 分析方法是否足够灵敏可以12.74 建立残留限度？ Microbiological aspects 微生物方面 Has inhibition of microbial growth by residue been considered during test method validation? 分析方法验证时是否考虑残留对微生物生长的抑制？ Has the effectiveness of cleaning/sanitization When processes and procedures been validated? 12.75, 5.21, 5.23 equipment including water Are “clean/dirty status” system have to be controlled for microbiological contamination, there shall be appropriately validated cleaning/sanitization procedures 如果工艺和设备，包括水系统均需要控制微生物，则应有经过适当验证的清洁/消毒程序 hold times and sanitizer residue limits correctly considered? Is the water used for cleaning/rinsing appropriate for the next manufacturing step? 清洁/消毒程序的有效性是否经过验证？“清洁/脏状态”保持时间和消毒后残留限度是否正确考虑？用于清洁/淋洗的水是否适用于下一生产步骤？ 13. Change Control 变更控制 Area of operations / items 操作区域/项目 Notes 注意点 关键问题/给我看 Supporting documents 支持性文件 Crucial questions/Show me Cf. Scope 4.2 13. 参见范围4.2 14. Rejection and re-use of materials 不合格物料和回用物料 Area of operations / items 操作区域/项目 Solvent and Specifications Notes 注意点 关键问题/给我看 Supporting documents 支持性文件 Crucial questions/Show me Has a rationale for solvent 14.41, 14.42 material Recovery appropriate for the / material specification 回收溶剂和物料 intended use 质量标准适合其用途 been documented? 溶剂/物料质量标准的合理性是否记录？ If it is to be used for 14.41 multiple processes, does the specification account for the presence of contaminants introduced from other processes? 如果用于多个工艺，质量标准是否考虑其它工艺来源的污染？ Outsourced services Is the level of control over 7.3, 16. are to be controlled the supplier of outsourced 外包服务需要进行控制 services appropriate? (see section 7.3); 对外包服务供应商的控制水平是否适当？（参见7.3部分） Documents and records Are relevant SOPs, batch must be maintained records and CoA available? Are recovered solvents 14.40, 14.43 文件和记录必须维护 formally approved and released for use? 是否有相应的SOP、批记录和分析报告？回收溶剂是否经过正式批准，在使用前放行？ Identification and Is the identification of 14.41, 14.43, controls of equipment the equipment used recorded 5.21 used for recovery, transportation and storage of solvents 用于溶剂回收、运输和存贮的设备应进行识别和控制 or cross referenced in the batch record? Are appropriate procedures in place to avoid mix-up and cross contamination? 所使用的设备识别号是否记录在批记录中，并可以交叉索引？是否有适当的程序以避免混淆和交叉污染？ Rejection 不合格拒收 Rejected APIs and intermediate materials shall be quarantined and recorded The disposition of material shall be recorded 不合格原料药和中间体物料应隔离并记录。物料处理应记录。 Do procedures exist and are 14.1 they adequate? How are materials identified and stored? Is a list of rejected materials maintained? Do the Certificates of Destruction for disposed materials correspond with the list of rejected materials? 是否有程序？程序是否充分？物料如何识别和存贮？是否保存有不合格物料清单？销售证明是否与不合格物料清单一致？ Reworking 再加工 Is an investigation performed before a decision to rework is carried out? 在决定实施再加工前，是否进行调查？ 14.30 Have reworked batches been 14.31 subjected to: -appropriate evaluation -stability testing -a review to show equivalency to original process? Is validation performed if more than one batch is affected? Is a report issued if only one batch is affected? 再加工批次是否： --适当评估 --进行稳定性试验 --审核说明其与原始工艺的等同性？ 如果不止一批受到影响，是否进行验证？如果只有一批受到影响是否签发一份报告？ The impurity profile Are the impurity profiles 14.32 of a reworked batch of reworked batches similar shall be comparable to to routine production routine batches 再加工批次的杂质谱应与常规生产批次的杂质谱具有可比性 production batches? 再加工批次的杂质谱是否与常规生产批次相似？ Additional testing Are routine analytical 14.32 and test methods if methods adequate for the routine test methods analysis of reworked are found to be batches? Will the methods inadequate 如果常规检测不充分，则应该有附加检测和检测方法 detect additional degradants or other impurities? 常规检测方法是否足以对再加工批次进行分析？方法是否能检出额外的降解产物或其它杂质？ Returns 退货 Policy on returns If the company accepts 14.50 documented 退货产品方针应记录 returns, are the returned APIs and intermediates identified as returns and subsequently quarantined? 如果公司接受了退货，退回的原料药和中间体是否标识为退货并进行相应隔离？ Records of returns Does the procedure for maintained 退货记录应维护 handling returned product require the reason for returning the product to be identified? 14.51, 14.52 Do the company’s records allow identification of the transportation and storage history of the product, whilst the product was outside the company’s control? Are the details recorded in the documentation associated with the returned product adequate and appropriate? Is returned product appropriately dispositioned for reprocessing, reworking, or destruction? 退货产品处理程序是否要求对退货原因进行识别？ 公司的记录是否可以跟踪产品在公司控制以外的运输和存贮历史？ 随货的文件是否记录足够详细适当？ 退货是否得到适当处理，返工、再加工或销毁？ 15. Complaints and Recalls 客诉和召回 Area of operations / items Crucial questions/Show me Supporting documents Notes 注意点 操作区域/项目 关键问题/给我看 Cf. Scope 4.2 参见范围4.2 支持性文件 15. 16. Contract manufacturers (including Laboratories) 合同生产商（包括化验室） Area of operations / items 操作区域/项目 Notes 注意点 Crucial questions/Show me 关键问题/给我看 Cf. Scope 4.2 参见范围4.2 Supporting documents 支持性文件 16. 17. Agents, Brokers, Traders, Distributors, Repackers and Relabellers 代理、经销商、贸易商、分销商、再包装和再标签商 Area of operations / items 操作区域/项目 General 一般 Relevant sections of Part II are applicable to Agents, Brokers, Traders and Distributors (e.g. chapters 2, 3, 4, 6, 7.4, 9, 10, 11.4, 14.52, 15). EU GMP第二部分的相关部分适用于代理、经销商、贸易商和分Notes 注意点 关键问题/给我看 Supporting documents 支持性文件 17.10, 17.11 Crucial questions/Show me 销商（例如第2，3，4，6，7.4，9，10，11.4，14.52，15部分） Repackers and relabellers are considered as manufacturers (full compliance with Part II required) 再包装和再标签商应作为生产商（符合EU GMP第二部分的要求） 17.11, 17.40 For some APIs, consider the 17.20 availability and completeness of required Traceability of APIs and intermediates 原料药和中间体可追踪性 Effectiveness the system 系统有效性 documentation back to the of original manufacturer Are these records readily available? 有些原料药，考虑到其所需的由生产商所提供文件可获得性和完整性，这些记录是否易于获得？ Transfer information 信息传递 of Is the customer informed of any additional manufacturing operation carried out on behalf of Agents, Brokers, Traders, Distributors, Repackers and 17.60 Relabellers (e.g. micronisation, Gamma irradiation, freeze-drying)? 代理、经销商、贸易商、分销商、再包装和再标签商对产品所作的附加生产操作（例如微粉化、伽马射线、冻干处理）是否通知客户？ Are the original API 9.43, 17.61 name, manufacturer’s address and the batch number(s) supplied provided to the customer? 原料药生产商的名称和地址、批号是否提供给客户？ Is the original API 11.44 manufacturer’s name and address included on the CoA and displayed on labels? 原料药生产名称和地址是否在分析报告和标签上显示？ Is quality or regulatory related information exchanged between partners in a timely manner? 在合作伙伴之间交换质量和法规相关信息是否及时？ 17.60 In case of quality related 17.71, 17.72 problems, are Agents, Brokers, Traders, Distributors, Repackers and Relabellers involved? Are they informed of any investigation and actions undertaken? 如果发生质量相关问题，代理商、分销商、贸易商、再包装和再标签商是否会被牵涉？所有调查和采取措施是否通知他们？ Repackaging relabelling 再包装、再标签 Do procedures, records, and 17.4 environmental monitoring indicate that controls are in place to avoid mix-up, contamination and cross-contamination? 程序、记录和环境监控是否可以避免混淆、污染和交叉污染？ Are samples retained? 11.7 样品是否保留？ Stability 稳定性 Is retest or expiry date available? When an API is repacked in a different type of container are the mandatory stability studies conducted? 是否有复验期和有效期？如果一个原料药分包装于不同类型17.20 17.50 的容器中，是否必须进行稳定性试验？ If micronisation, Gamma irradiation, freeze-drying is performed on behalf of the Agents, Brokers, Traders, Distributors, Repackers and Relabellers are the mandatory stability studies conducted according to section 11.5? 如果由代理商、分销商、再包装和再标签商进行了微粉、伽马辐射、冻干处理，则根据11.5是否必须进行稳定性试验？ 17.50 11.5 18. APIs manufactured by Cell Culture / Fermentation 细胞培养/发酵生产原料药 Area of operations / items 操作区域/项目 Notes 注意点 Crucial questions/Show me 关键问题/给我看 See PIC/S Aide Memoire PI-024 参见PIC/S备忘PI-024 Supporting documents 支持性文件
因篇幅问题不能全部显示，请点此查看更多更全内容