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2018年6月20日，PIC / S 官网发布了新的GMP指南（PE 009-14），新的指南修订了以下章节和附录： 第三章：“厂房和设备” 第五章：“生产” 第八章：“投诉和召回” 附录17：“实时放行检验和参数放行” 修订后的GMP指南（PE 009-14）将于2018年7月1日生效。 新增及修订的条款翻译如下，GMP办公室对具体条款的修订情况进行了对比，点击文章底部“阅读原文”查看： PE 009-14 PIC/S GMP GUIDE PIC/S GMP指南 CHAPTER 3 PREMISES AND EQUIPMENT 第三章 厂房设施和设备
Production Areas 生产区
3.6 Cross-contamination should be prevented for all products by appropriate design and operation of manufacturing facilities. The measures to prevent cross-contamination should be commensurate with the risks. Quality Risk Management principles should be used to assess and control the risks. 应对生产设施采用适当的设计和操作以避免任何产品之间的交叉污染。防止交叉污染的措施应与风险相适应。应采用质量风险管理原则对这些风险进行评估和控制。
Depending of the level of risk, it may be necessary to dedicate premises and equipment for manufacturing and/or packaging operations to control the risk presented by some medicinal products. 根据风险的水平，生产和/或包装操作应有专用的厂房设施及设备以控制来自其他产品的风险 Dedicated facilities are required for manufacturing when a medicinal product presents a risk because: 当产品因下列原因存在风险时，应使用专用设施进行生产：
i. the risk cannot be adequately controlled by operational and/ or technical measures, 风险无法通过操作和/或技术措施充分控制
ii. scientific data from the toxicological evaluation does not support a controllable risk (e.g. allergenic potential from highly sensitising materials such as beta-lactams) or 来自毒性评价的科学数据无法支持风险的可控性（例如，高致敏性物料，如β酰胺类）或
iii. relevant residue limits, derived from the toxicological evaluation, cannot be satisfactorily determined by a validated analytical method. 由毒性评价数据推倒出来的残留限度尚无有效的分析方法实现检测。
Further guidance can be found in Chapter 5 and in Annexes 2, 3, 4, 5 & 6. 更多指南详见章节5和附录2、3、4、5&6.
CHAPTER 5 PRODUCTION 第五章 生产
PREVENTION OF CROSS-CONTAMINATION IN PRODUCTION 防止生产过程交叉污染
5.17. Normally, the production of non-medicinal products should be avoided in areas and with equipment destined for the production of medicinal products but, where justified, could be allowed where the measures to prevent cross-contamination with medicinal products described below and in Chapter 3 can be applied. The production and/or storage of technical poisons, such as pesticides (except where these are used for manufacture of medicinal products) and herbicides, should not be allowed in areas used for the manufacture and / or storage of medicinal products. 通常，用于生产药品的设备和区域不得用于非药物产品生产，但是，如有充分理由，应用下列和第3章所述的防止药品交叉污染措施的情况下，允许生产非药物产品。技术性毒药生产和/或存储区域，如杀虫剂（除非用于制造医药产品的地方）和除草剂，不得用于药品生产和/或储存。
5.18. Contamination of a starting material or of a product by another material or product should be prevented. This risk of accidental cross-contamination resulting from the uncontrolled release of dust, gases, vapours, aerosols, genetic material or organisms from active substances, other materials (starting or in-process), and products in process, from residues on equipment, and from operators’ clothing should be assessed. The significance of this risk varies with the nature of the contaminant and that of the product being contaminated. Products in which cross-contamination is likely to be most significant are those administered by injection and those given over a long time. However, contamination of all products poses a risk to patient safety dependent on the nature and extent of contamination. 应防止起始物料或产品的被其他物料或产品污染。应评估来自生产过程中活性物质、其他物料（起始物料或生产过程物料）、产品的粉尘、气体、汽体、雾滴、基因物质或生物的非受控释放；设备残留；和操作人员衣服导致的潜在交叉污染风险。风险的严重性因污染物和受污染产品的性质而不同。那些通过注射给药和那些需要长期给药的产品的交叉污染则更为重要。但是，任何产品的污染都会导致病人用药安全的风险，取决于污染的性质和程度。
5.19. Cross-contamination should be prevented by attention to design of the premises and equipment as described in Chapter 3. This should be supported by attention to process design and implementation of any relevant technical or organizational measures, including effective and reproducible cleaning processes to control risk of cross-contamination. 厂房设施和设备的设计应关注防止交叉污染，见章节3。这应依靠对工艺设计和实施任何相关技术和组织措施的关注，包括有效并可重现的清洁工艺以控制交叉污染的风险。
5.20 A Quality Risk Management process, which includes a potency and toxicological evaluation, should be used to assess and control the cross-contamination risks presented by the products manufactured. Factors including; facility/equipment design and use, personnel and material flow, microbiological controls, physico-chemical characteristics of the active substance, process characteristics, cleaning processes and analytical capabilities relative to the relevant limits established from the evaluation of the products should also be taken into account. The outcome of the Quality Risk Management process should be the basis for determining the necessity for and extent to which premises and equipment should be dedicated to a particular product or product family. This may include dedicating specific product contact parts or dedication of the entire manufacturing facility. It may be acceptable to confine manufacturing activities to a segregated, self-contained production area within a multiproduct facility, where justified. 应使用质量风险管理流程，包括有效性和毒理学评价，来评估和控制所生产产品的交叉污染风险。设施/设备设计和使用，人流物流，微生物控制，活性物质的理化特性，工艺特性，清洁工艺和分析能力与通过产品评价建立的相关限度等因素也应被考虑。质量风险管理流程的结果应作为决定哪些厂房设施和设备应被专用于某一产品或某类产品的必要性和程度的基础。这可能包括专用特定产品接触部件或专用整个生产设施。在合理情况下，在多产品设施里面限制生产活动在一个隔离、独立的生产区域可能是可接受的。
5.21 The outcome of the Quality Risk Management process should be the basis for determining the extent of technical and organisational measures required to control risks for cross-contamination. These could include, but are not limited to, the following: 质量风险管理流程的结果应作为决定用以控制交叉污染风险的技术和组织措施的程度。这包括但不限于，如下：
Technical Measures 技术措施
i. Dedicated manufacturing facility (premises and equipment); 专用生产设施（厂房设施和设备） ii. Self-contained production areas having separate processing equipment and separate heating, ventilation and air-conditioning (HVAC) systems. It may also be desirable to isolate certain utilities from those used in other areas; 独立生产区域，配备单独的生产设备和单独的暖通空调系统（HVAC）。可以将特定公用系统独立于其他区域。 iii. Design of manufacturing process, premises and equipment to minimize risk for cross-contamination during processing, maintenance and cleaning; 生产工艺，厂房设施和设备设计以减少生产、维护和清洁过程中的交叉污染风险。 iv. Use of “closed systems” for processing and material/product transfer between equipment; 使用“封闭式系统”进行生产和设备间物料/产品转运 v. Use of physical barrier systems, including isolators, as containment measures; 使用物理屏障系统作为限制措施，包括隔离器。 vi. Controlled removal of dust close to source of the contaminant e.g. through localised extraction; 污染源附近的粉尘应得到受控的清除，例如，通过除尘罩。 vii. Dedication of equipment, dedication of product contact parts or dedication of selected parts which are harder to clean (e.g. filters), dedication of maintenance tools; 专用设备、专用产品接触部件或者专用难以清洁的部件，专用维修工具。 viii. Use of single use disposable technologies; 应用一次性使用技术 ix. Use of equipment designed for ease of cleaning; 使用设计以易于清洁的设备 x. Appropriate use of air-locks and pressure cascade to confine potential airborne contaminant within a specified area; 使用合适的气闸和压差梯度将潜在的污染物尘埃限制在某一特定区域 xi. Minimising the risk of contamination caused by recirculation or re-entry of untreated or insufficiently treated air; 将未经处理或未充分处理的空气再循环或再次进入空调系统导致的污染风险降至最低。 xii. Use of automatic clean in place systems of validated effectiveness; 使用经验证的自动在线清洗系统 xiii. For common general wash areas, separation of equipment washing, drying and storage areas. 对于公用一般清洗区域，专用设备清洗、干燥和存放区域。
Organisational Measures 组织措施
i. Dedicating the whole manufacturing facility or a self-contained production area on a campaign basis (dedicated by separation in time) followed by a cleaning process of validated effectiveness; 在某一生产阶段专用整个生产设施或一个独立的生产区域（错开时间实现专用），然后进行清洁，清洁工艺需经验证有效。 ii. Keeping specific protective clothing inside areas where products with high risk of cross-contamination are processed; 在具有高度交叉污染风险的产品处理区域内保持特定的防护服 iii. Cleaning verification after each product campaign should be considered as a detectability tool to support effectiveness of the Quality Risk Management approach for products deemed to present higher risk; 应在每次生产活动后进行清洁确认，应考虑可检测的方法，以支持被认为存在较高风险的产品的质量风险管理方法的有效性 iv. Depending on the contamination risk, verification of cleaning of non product contact surfaces and monitoring of air within the manufacturing area and/or adjoining areas in order to demonstrate effectiveness of control measures against airborne contamination or contamination by mechanical transfer; 根据污染的风险，确认非产品接触表面的清洁并监测生产区域内和/或相邻区域的空气以证实空气污染或设备转运污染的控制措施的有效性。 v. Specific measures for waste handling, contaminated rinsing water and soiled gowning; 废弃物处理、污染冲洗水和脏手套的特殊措施 vi. Recording of spills, accidental events or deviations from procedures; 记录泄漏、意外事故或偏离规程的偏差 vii. Design of cleaning processes for premises and equipment such that the cleaning processes in themselves do not present a cross-contamination risk; 设计厂房设施和设备的清洁工艺以使清洁工艺本身存在交叉污染风险。 viii. Design of detailed records for cleaning processes to assure completion of cleaning in accordance with approved procedures and use of cleaning status labels on equipment and manufacturing areas; 设计清洁工艺的详细记录以确保清洁完整符合批准的规程并在设备和生产区域使用清洁状态标识。 ix. Use of common general wash areas on a campaign basis; 在某一生产阶段使用共用一般清洗区域 x. Supervision of working behaviour to ensure training effectiveness and compliance with the relevant procedural controls. 监督工作行为以确保培训效果并符合相关程序控制。
STARTING MATERIALS 起始物料
5.27 The selection, qualification, approval and maintenance of suppliers of starting materials, together with their purchase and acceptance, should be documented as part of the pharmaceutical quality system. The level of supervision should be proportionate to the risks posed by the individual materials, taking account of their source, manufacturing process, supply chain complexity and the final use to which the material is put in the medicinal product. The supporting evidence for each supplier / material approval should be maintained. Staff involved in these activities should have a current knowledge of the suppliers, the supply chain and the associated risks involved. Where possible, starting materials should be purchased directly from the manufacturer of the starting material. 起始物料供应商的选择、确认、批准和维护，以及购买和验收，应有文件规定，作为制药质量体系的一部分。监督的水平应与物料的风险相适应，考虑其来源、生产工艺、供应链完整性及其在药品中的最终用途。应保存每一供应商/物料批准的支持性证据。从事这些活动的人员应拥有对供应商、供应链和相关风险的最新知识。如可能，其实物料应直接从起始物料供应商处购买。
5.28 The quality requirements established by the manufacturer for the starting materials should be discussed and agreed with the suppliers. Appropriate aspects of the production, testing and control, including handling, labelling, packaging and distribution requirements, complaints, recalls and rejection procedures should be documented in a formal quality agreement or specification. 生产商建立的对起始物料的质量要求应与供应商讨论并达成一致。应在正式的质量协议或规范中规定生产、检验和控制的有关方面，包括处理、贴标、包装和运输要求、投诉、召回和拒签程序。
5.29 For the approval and maintenance of suppliers of active substances and excipients, the following is required: 对于活性成分和辅料供应商的批准和维护，应符合如下要求： Active substances 活性成分 Supply chain traceability should be established and the associated risks, from active substance starting materials to the finished medicinal product, should be formally assessed and periodically verified. Appropriate measures should be put in place to reduce risks to the quality of the active substance. 应建立供应链的可追溯性并且相关风险，从活性成分起始物料到成品，应被正式评估并定期确认。应有适当措施降低活性成分的质量风险。
The supply chain and traceability records for each active substance (including active substance starting materials) should be available and be retained by the manufacturer of the medicinal product. 应有每一活性成分（包括活性成分起始物料）的供应链和可追溯记录，并由药品生产商保存。
Audits should be carried out at the manufacturers and distributors of active substances to confirm that they comply with the relevant good manufacturing practice and good distribution practice requirements. The holder of the manufacturing authorisation shall verify such compliance either by himself/herself or through an entity acting on his/her behalf under a contract. For veterinary medicinal products, audits should be conducted based on risk. 应对活性成分生产商和分销商进行审计以确认其符合相关GMP/GDP要求。生产许可持有人应自行或通过合同第三方对此进行确认。对于兽用药物产品，应基于风险进行审计。
Audits should be of an appropriate duration and scope to ensure that a full and clear assessment of GMP is made; consideration should be given to potential cross- contamination from other materials on site. The report should fully reflect what was done and seen on the audit with any deficiencies clearly identified. Any required corrective and preventive actions should be implemented. 审计应有适当的持续时间和范围以确保进行完整清晰的GMP评估。应考虑与工厂其他物料之间的潜在交叉污染。报告应充分反应审计时做了什么、看到了什么以及发现了哪些缺陷。任何要求的纠正和预防措施应得到实施。
Further audits should be undertaken at intervals defined by the quality risk management process to ensure the maintenance of standards and continued use of the approved supply chain. 后续审计应通过质量风险管理流程定期开展以确保标准的维护和经批准供应链的持续使用。
Excipients 辅料
Excipients and excipient suppliers should be controlled appropriately based on the results of a formalised quality risk assessment in accordance with the PIC/S Guideline PI 045-1 ‘Guidelines on the formalised risk assessment for ascertaining the appropriate Good Manufacturing Practice for excipients of medicinal products for human use’. 应基于一份正式的质量风险评估的结果对辅料和辅料供应商进行适当控制，根据PIC / S指南PI 045-1“确定人用药用辅料适用GMP的正式风险评估指南”进行。
5.30 For each delivery of starting material the containers should be checked for integrity of package, including tamper evident seal where relevant, and for correspondence between the delivery note, the purchase order, the supplier’s labels and approved manufacturer and supplier information maintained by the medicinal product manufacturer. The receiving checks on each delivery should be documented. 对于起始物料的每一次交付，应检查容器包装完整性，包括开启留痕签（如有），以及提货单、购买订单、供应商标签和药品生产商维护的已批准生产商和供应商信息之间的一致性。每一次交付均应记录接收检查。
5.34 Only starting materials which have been released by the Quality Control Department and which are within their retest date should be used. 只有当起始物料得到QC部门放行并在其复验期内，才可以被使用。
5.35 Manufacturers of finished products are responsible for any testing of starting materials3 as described in the marketing authorisation dossier. They can utilise partial or full test results from the approved starting material manufacturer but must, as a minimum, perform identification testing4 of each batch according to Annex 8. 制剂成品生产商负责起始物料的所有检验。他们可以使用起始物料供应商的部分或全部检验结果，但前提是，至少，根据附录8对每一批次进行鉴别检验。
注： 3 A similar approach should apply to packaging materials as stated in section 5.45. 类似方法适用于包装材料，见5.45. 4 Identity testing of starting materials should be performed according to the methods and the specifications of the relevant marketing authorisation dossier. 起始物料的鉴别检验应按照相关上市许可档案中描述的方法和标准进行。
5.36 The rationale for the outsourcing of this testing should be justified and documented and the following requirements should be fulfilled: 应论证使用外包机构来执行这些检验的合理性并进行记录，应满足如下要求：
i. Special attention should be paid to the distribution controls (transport, wholesaling, storage and delivery) in order to maintain the quality characteristics of the starting materials and to ensure that test results remain applicable to the delivered material; 应特别关注运输控制（运输、分发、储存和交付）以保持起始物料的质量特性并确保检验结果仍然能够代表说交付的物料。 ii. The medicinal product manufacturer should perform audits, either itself or via third parties, at appropriate intervals based on risk at the site(s) carrying out the testing (including sampling) of the starting materials in order to assure compliance with Good Manufacturing Practice and with the specifications and testing methods described in the marketing authorisation dossier; 药品生产商应基于风险在适当间隔对执行检验（包括取样）的场地进行审计，亲自或通过第三方机构，以确保符合GMP和上市许可档案中描述的标准和检验方法。 iii. The certificate of analysis provided by the starting material manufacturer/supplier should be signed by a designated person with appropriate qualifications and experience. The signature assures that each batch has been checked for compliance with the agreed product specification unless this assurance is provided separately; 起始物料生产商/供应商提供的检验报告书（COA）应由经过适当确认和经验的指定人员签名。签名应确保每个批次都经过检查符合商定的产品标准，除非另有规定。 iv. The medicinal product manufacturer should have appropriate experience in dealing with the starting material manufacturer (including experience via a supplier) including assessment of batches previously received and the history of compliance before reducing in-house testing. Any significant change in the manufacturing or testing processes should be considered; 药品生产商应具有处理起始物料生产商的适当经验（包括通过供应商的经验），包括评估先前收到的批次以及在减少内部检验之前的合规历史。任何生产或检验过程的重大变更均应被考虑。 v. The medicinal product manufacturer should also perform (or via a separately approved contract laboratory) a full analysis at appropriate intervals based on risk and compare the results with the material manufacturer’s or supplier’s certificate of analysis in order to check the reliability of the latter. Should this testing identify any discrepancy then an investigation should be performed and appropriate measures taken. The acceptance of certificates of analysis from the material manufacturer or supplier should be discontinued until these measures are completed. 药品生产商还应根据风险在适当的时间间隔内（或通过单独批准的合同实验室）进行全面检验，并将结果与物料生产商或供应商的检验证书（COA）进行比较，以检查后者的可靠性。 如果此测试发现任何差异，则应执行调查并采取适当措施。 在这些措施完成之前，来自物料生产商或供应商的检验报告书应不得再接受。
PACKAGING MATERIALS 包装材料
5.45 The selection, qualification, approval and maintenance of suppliers of primary and printed packaging materials shall be accorded attention similar to that given to starting materials. 内包材和印字包材供应商的选择、确认、批准和维持应给予与起始物料类似的关注。
PRODUCT SHORTAGE DUE TO MANUFACTURING CONSTRAINTS 由于制造约束导致产品短缺
5.71 The manufacturer should report to the marketing authorisation holder (MAH) any constraints in manufacturing operations which may result in abnormal restriction in the supply. This should be done in a timely manner to facilitate reporting of the restriction in supply by the MAH, to the relevant competent authorities, in accordance with its legal obligations. 生产商应向上市许可持有人（MAH）报告任何可能导致供应异常限制的制约因素。 这应及时进行，以便于MAH根据其法律义务向有关主管部门报告供应限制。
CHAPTER 8 COMPLAINTS AND PRODUCT RECALL 第八章 投诉和产品召回
PRINCIPLE 原则
In order to protect public and animal health, a system and appropriate procedures should be in place to record, assess, investigate and review complaints including potential quality defects, and if necessary, to effectively and promptly recall medicinal products for human or veterinary use and investigational medicinal products from the distribution network. Quality Risk Management principles should be applied to the investigation and assessment of quality defects and to the decision-making process in relation to product recalls corrective and preventative actions and other risk-reducing actions. Guidance in relation to these principles is provided in Chapter 1. 为确保公众和动物安全，应有一个系统和适当的规程来记录、评估、调查和回顾投诉，包括潜在的质量影响，和必要时，迅速有效地从分销网络上召回人用/兽用/临床试验用药品。应使用质量风险管理原则来调查和评估质量影响，并运用于产品召回纠正和预防措施以及其他风险降低行动的决策流程。有关这些原则的指南见章节1.
All concerned Competent Authorities should be informed in a timely manner in case of a confirmed quality defect (faulty manufacture, product deterioration, detection of falsification, non-compliance with the marketing authorisation or product specification file, or any other serious quality problems) with a medicinal or investigational medicinal product which may result in the recall of the product or an abnormal restriction in the supply. In situations where product on the market is found to be non-compliant with the marketing authorisation, there may be a requirement to notify concerned Competent Authorities. Reference should be made to relevant legislative requirements. 一旦确定药品或临床试验用药品存在可能导致产品召回或供应异常的质量缺陷（生产缺陷、产品变质、发现造假、不符合上市许可或产品标准文件、或任何其他严重质量问题），应及时通知所有有关监管机构。在市售产品中发现不符合上市许可的情况下，应通知有关监管当局。应参考有关的立法规定。
In case of outsourced activities, a contract should describe the role and responsibilities of the manufacturer, the marketing authorisation holder and/or sponsor and any other relevant third parties in relation to assessment, decision-making, and dissemination of information and implementation of risk-reducing actions relating to a defective product. Guidance in relation to contracts is provided in Chapter 7. Such contracts should also address how to contact those responsible at each party for the management of quality defect and recall issues. 如是外包活动，合同中应描述生产商、上市许可持有人和/或赞助商和其他相关第三方机构在有关缺陷产品的评估、决策、以及信息传递和实施风险降低措施方面的角色和责任。有关合同的指南见章节7。该合同还应包括如何联系各方负责的质量缺陷管理和召回问题。
PERSONNEL AND ORGANISATION 人员和组织
8.1 Appropriately trained and experienced personnel should be responsible for managing complaint and quality defect investigations and for deciding the measures to be taken to manage any potential risk(s) presented by those issues, including recalls. These persons should be independent of the sales and marketing organisation, unless otherwise justified. If these persons do not include the Authorised Person involved in the certification for release of the concerned batch or batches, the latter should be made formally aware of any investigations, any risk-reducing actions and any recall operations, in a timely manner. 应由经适当培训和经验的人员负责投诉管理和质量缺陷调查，负责决定需要采取的措施管理这些问题所带来的任何潜在风险，包括召回。这些人员应独立于销售和市场部门，除非有其他合理理由。如果这些人员未包括从事有关批次放行的许可人，则后者应及时正式地了解任何调查，风险降低措施和召回行动。
8.2 Sufficient trained personnel and resources should be made available for the handling, assessment, investigation and review of complaints and quality defects and for implementing any risk-reducing actions. Sufficient trained personnel and resources should also be available for the management of interactions with Competent Authorities. 应有经过充分培训的人员和资源来处理、评估、调查和回顾投诉和质量缺陷，并实施任何风险降低措施。与监管当局接触也同样需要经过充分培训的人员和资源。
8.3 The use of inter-disciplinary teams should be considered, including appropriately trained Quality Management personnel. 应考虑使用跨学科团队，包括经适当培训的质量管理人员。
8.4 In situations in which complaint and quality defect handling is managed centrally within an organisation, the relative roles and responsibilities of the concerned parties should be documented. Central management should not, however, result in delays in the investigation and management of the issue. 在投诉和质量缺陷处理由一个组织集中管理的情况下，应规定各相关方的角色和职责。集中管理不应导致调查和问题管理的延误。
PROCEDURES FOR HANDLING AND INVESTIGATING COMPLAINTS INCLUDING POSSIBLE QUALITY DEFECTS 投诉处理和调查程序，包括可能的质量缺陷
8.5 There should be written procedures describing the actions to be taken upon receipt of a complaint. All complaints should be documented and assessed to establish if they represent a potential quality defect or other issue. 应有书面规程描述收到投诉后需要采取的行动。所有投诉应被记录并评估以确定是否有潜在的质量缺陷或其他问题。
8.6 Special attention should be given to establishing whether a complaint or suspected quality defect relates to falsification. 应特别关注投诉或可疑质量缺陷是否与造假有关。
8.7 As not all complaints received by a company may represent actual quality defects, complaints which do not indicate a potential quality defect should be documented appropriately and communicated to the relevant group or person responsible for the investigation and management of complaints of that nature, such as suspected adverse events. 由于并非公司收到的所有投诉都可能代表实际的质量缺陷，因此，没有显示出潜在质量缺陷的投诉应予以适当记录并通知负责调查和管理此类投诉的相关团队或个人，例如可疑不良事件。
8.8 There should be procedures in place to facilitate a request to investigate the quality of a batch of a medicinal product in order to support an investigation into a reported suspected adverse event. 应该制定规程以便于调查一批药品的质量，以支持对所报告的可疑不良事件进行调查。
8.9 When a quality defect investigation is initiated, procedures should be in place to address at least the following: 进行质量缺陷调查时，应有规程至少规定如下内容：
i. The description of the reported quality defect. 报告的质量缺陷的描述 ii. The determination of the extent of the quality defect. The checking or testing of reference and/or retention samples should be considered as part of this, and in certain cases, a review of the batch production record, the batch certification record and the batch distribution records (especially for temperature-sensitive products) should be performed. 确定质量缺陷的程度。应将标准和/或留样样品的检查或检验作为其中的一部分，在某些情况下，应审查批生产记录，批放行记录和批次分销记录（特别是对于温度敏感型产品）。
iii. the need to request a sample, or the return, of the defective product from the complainant and, where a sample is provided, the need for an appropriate evaluation to be carried out. 需要向投诉人索取样品或退回有缺陷的产品，并且在拿到样品后，需要进行适当的评价。
iv. The assessment of the risk(s) posed by the quality defect, based on the severity and extent of the quality defect. 根据质量缺陷的严重程度和范围评估质量缺陷造成的风险。 v. The decision-making process that is to be used concerning the potential need for risk-reducing actions to be taken in the distribution network, such as batch or product recalls, or other actions. 关于从分销网络中采取风险降低措施的潜在需求（例如批次或产品召回）或其他行动的决策过程。
vi. The assessment of the impact that any recall action may have on the availability of the medicinal product to patients/animals in any affected market, and the need to notify the relevant authorities of such impact. 评估召回行动对受影响市场患者/动物的药品可用性的影响，以及需要将此类影响通知有关当局。
vii. The internal and external communications that should be made in relation to a quality defect and its investigation. 应该就质量缺陷及其调查进行内部和外部沟通。
viii. The identification of the potential root cause(s) of the quality defect. 确定质量缺陷的潜在根本原因。
ix. The need for appropriate Corrective and Preventive Actions (CAPAs) to be identified and implemented for the issue, and for the assessment of the effectiveness of those CAPAs. 就此问题确定和实施适当的纠正和预防行动（CAPAs），并评估这些CAPAs的有效性。
INVESTIGATION AND DECISION-MAKING 调查和决策
8.10 The information reported in relation to possible quality defects should be recorded, including all the original details. The validity and extent of all reported quality defects should be documented and assessed in accordance with Quality Risk Management principles in order to support decisions regarding the degree of investigation and action taken. 应记录所报告的与可能的质量缺陷有关的信息，包括所有原始细节。 所有报告的质量缺陷的有效性和范围应根据质量风险管理原则进行记录和评估，以支持与采取调查和措施程度的决定。
8.11 If a quality defect is discovered or suspected in a batch, consideration should be given to checking other batches and in some cases other products, in order to determine whether they are also affected. In particular, other batches which may contain portions of the defective batch or defective components should be investigated. 如果在批次中发现或怀疑质量缺陷，则应考虑检查其他批次和某些情况下的其他产品，以确定它们是否也受到影响。 特别是，应调查其他可能含有有缺陷批次或有缺陷成分的批次。
8.12 Quality defect investigations should include a review of previous quality defect reports or any other relevant information for any indication of specific or recurring problems requiring attention and possibly further regulatory action. 质量缺陷调查应包括审查以前的质量缺陷报告或任何其他相关信息，以指出需要关注的特定问题或频繁出现的问题以及可能采取的进一步管制行动。
8.13 The decisions that are made during and following quality defect investigations should reflect the level of risk that is presented by the quality defect as well as the seriousness of any non-compliance with respect to the requirements of the marketing authorisation/product specification file or GMP. Such decisions should be timely to ensure that patient and animal safety is maintained, in a way that is commensurate with the level of risk that is presented by those issues. 在质量缺陷调查过程中及之后作出的决定应该反映质量缺陷的风险水平，以及任何不符合上市许可/产品标准文件或GMP要求的严重性。 这些决定应该及时，以确保患者和动物的安全，并且与这些问题所呈现的风险水平相称。
8.14 As comprehensive information on the nature and extent of the quality defect may not always be available at the early stages of an investigation, the decision-making processes should still ensure that appropriate risk-reducing actions are taken at an appropriate time-point during such investigations. All the decisions and measures taken as a result of a quality defect should be documented. 由于在调查的早期阶段可能并不能获取质量缺陷的性质和范围的全面信息，因此决策过程仍应确保在调查期间的适当时间点采取适当的风险降低措施。应记录所有因质量缺陷而采取的决定和措施。
8.15 Quality defects should be reported in a timely manner by the manufacturer to the marketing authorisation holder/sponsor and all concerned Competent Authorities in cases where the quality defect may result in the recall of the product or in an abnormal restriction in the supply of the product. 在质量缺陷可能导致产品召回或产品供应异常限制的情况下，质量缺陷应由生产商及时向上市许可持有人/发起人和所有相关主管当局报告。
ROOT CAUSE ANALYSIS AND CORRECTIVE AND PREVENTATIVE ACTIONS 根本原因分析和纠正预防措施
8.16 An appropriate level of root cause analysis work should be applied during the investigation of quality defects. In cases where the true root cause(s) of the quality defect cannot be determined, consideration should be given to identifying the most likely root cause(s) and to addressing those. 在质量缺陷调查过程中应进行适当水平的根本原因分析。如无法确定质量缺陷的真实根本原因，应考虑确定最可能的根本原因并解决这些问题。
8.17 Where human error is suspected or identified as the cause of a quality defect, this should be formally justified and care should be exercised so as to ensure that process, procedural or system-based errors or problems are not overlooked, if present. 如果怀疑或认定人为错误是造成质量缺陷的原因，则应正式说明理由，并应注意保证工艺，程序或系统错误或问题不会被忽视（如果存在）。
8.18 Appropriate CAPAs should be identified and taken in response to a quality defect. The effectiveness of such actions should be monitored and assessed. 应该确定适当的CAPAs并实施以应对质量缺陷。 应监测和评估此类行为的有效性
8.19 Quality defect records should be reviewed and trend analyses should be performed regularly for any indication of specific or recurring problems requiring attention. 应该回顾质量缺陷记录，并定期进行趋势分析，以指出需要注意的特定或反复出现的问题。
PRODUCT RECALLS AND OTHER POTENTIAL RISK-REDUCING ACTIONS 产品召回和其他潜在风险降低措施
8.20 There should be established written procedures, regularly reviewed and updated when necessary, in order to undertake any recall activity or implement any other risk-reducing actions. 应制定书面规程，在必要时定期审查和更新，以便开展任何召回活动或实施任何其他减少风险的行动。
8.21 After a product has been placed on the market, any retrieval of it from the distribution network as a result of a quality defect should be regarded and managed as a recall. (This provision does not apply to the retrieval (or return) of samples of the product from the distribution network to facilitate an investigation into a quality defect issue/report.) 产品流入市场后，任何由于质量缺陷而从分销网络中取回产品应作为召回对待及管理。（本条款不适用于从分销网络中取回（或退回）产品样品，以便调查质量缺陷问题/报告。）
8.22 Recall operations should be capable of being initiated promptly and at any time. In certain cases recall operations may need to be initiated to protect public or animal health prior to establishing the root cause(s) and full extent of the quality defect 召回行动应该能够在任何时候及时发起。在某些情况下，可能需要启动召回行动，以在确定根本原因和质量缺陷全部范围之前保护公众或动物健康。
8.23 The batch/product distribution records should be readily available to the persons responsible for recalls, and should contain sufficient information on wholesalers and directly supplied customers (with addresses, phone and/or fax numbers inside and outside working hours, batches and amounts delivered), including those for exported products and medical samples. 批次/产品分销记录应随时提供给召回责任人员，并应包含有关批发商和直接供应客户的足够信息（地址，工作时间内外的电话和/或传真号码，批次和交付金额）， 包括出口产品和药物样品。
8.24 In the case of investigational medicinal products, all trial sites should be identified and the countries of destination should be indicated. In the case of an investigational medicinal product for which a marketing authorisation has been issued, the manufacturer of the investigational medicinal product should, in cooperation with the sponsor, inform the marketing authorisation holder of any quality defect that could be related to the authorised medicinal product. The sponsor should implement a procedure for the rapid unblinding of blinded products, where this is necessary for a prompt recall. The sponsor should ensure that the procedure discloses the identity of the blinded product only in so far as is necessary. 对于临床试验用药品，应确定所有试验场地，并指明目的地国家。对于已获得上市许可的临床试验用药品，临床试验用药品生产商应与主办方合作，将任何可能与授权医药产品有关的质量缺陷告知上市许可持有人。申办者应该实施盲法产品快速揭盲的程序，以便及时召回。 申办者应确保该程序只在必要时才公开该盲品的身份。
8.25 Consideration should be given following consultation with the concerned Competent Authorities, as to how far into the distribution network a recall action should extend, taking into account the potential risk to public or animal health and any impact that the proposed recall action may have. The Competent Authorities should also be informed in situations in which no recall action is being proposed for a defective batch because the batch has expired (such as with short shelf-life products.) 考虑到公众或动物健康的潜在风险以及拟议召回行动可能产生的任何影响，在与有关主管部门协商后，应考虑召回行动应扩展到分销网络的多远。 如果因为批次已经过期（例如保质期较短的产品）而没有针对有缺陷批次提出召回行动，也应通知主管部门。
8.26 All concerned Competent Authorities should be informed in advance in cases where products are intended to be recalled. For very serious issues (i.e. those with the potential to seriously impact upon patient or animal health), rapid risk-reducing actions (such as a product recall) may have to be taken in advance of notifying the Competent Authorities. Wherever possible, attempts should be made to agree these in advance of their execution with the concerned Competent Authorities 产品召回应事先通知所有有关主管部门。对于非常严重的问题（即可能严重影响患者或动物健康的问题），则紧急风险降低措施（如产品召回）可能等不及通知主管当局。 在可能的情况下，应尽量在执行之前与有关主管部门达成一致
8.27 It should also be considered whether the proposed recall action may affect different markets in different ways, and if this is the case, appropriate market-specific risk-reducing actions should be developed and discussed with the concerned Competent Authorities. Taking account of its therapeutic use the risk of shortage of a medicinal product which has no authorised alternative should be considered before deciding on a risk-reducing action such as a recall. Any decisions not to execute a risk-reducing action which would otherwise be required should be agreed with the Competent Authority in advance. 还应该考虑拟召回行动是否可能以不同的方式影响不同的市场，如果是这种情况，应该制定适当的针对具体市场的风险降低行动，并与有关主管部门进行讨论。考虑到其治疗用途，在决定风险降低行动（如召回）之前，应考虑没有许可替代品的药品短缺风险。若决定不执行本应要求的风险降低措施，应事先与主管部门商定。
8.28 Recalled products should be identified and stored separately in a secure area while awaiting a decision on their fate. A formal disposition of all recalled batches should be made and documented. The rationale for any decision to rework recalled products should be documented and discussed with the relevant Competent Authority. The extent of shelf-life remaining for any reworked batches that are being considered for placement onto the market should also be considered. 被召回的产品在作出处理决定前，应在安全区域内单独标识和存储。应对所有召回的批次进行正式处置并记录在案。任何决定对召回产品进行重新加工的理由应该记录下来并与有关主管当局讨论。 应考虑投放市场的任何重新加工批次的剩余货架期。
8.29 The progress of the recall process should be recorded until closure and a final report issued, including a reconciliation between the delivered and recovered quantities of the concerned products/batches. 召回过程的进展应记录在案，直至关闭并发布最终报告，包括对相关产品/批次的交付量和回收量进行衡算。
8.30 The effectiveness of the arrangements in place for recalls should be periodically evaluated to confirm that they remain robust and fit for use. Such evaluations should extend to both within office-hour situations as well as out-of-office hour situations and, when performing such evaluations, consideration should be given as to whether mock-recall actions should be performed. This evaluation should be documented and justified. 应定期评估已制定的召回部署的有效性，以确保其保持健全并适合使用。这种评估应该覆盖办公时间及休息时间的情况，并且在进行这种评估时，应考虑是否应该执行模拟召回行动。这种评估应该形成文件并进行论证。
8.31 In addition to recalls, there are other potential risk-reducing actions that may be considered in order to manage the risks presented by quality defects. Such actions may include the issuance of cautionary communications to healthcare professionals in relation to their use of a batch that is potentially defective. These should be considered on a case-by-case basis and discussed with the concerned Competent Authorities. 除了召回之外，为了管理质量缺陷带来的风险，还可以考虑其他潜在的风险降低措施。此类行为可能包括向医疗保健专业人员发出使用可能存在缺陷的批次相关的警告信息。应根据具体情况考虑这些问题并与有关主管当局进行讨论 |
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