EC-012-Eu GMP 中文版

Eu GMP

第I 部分为药品制造的GMP

Principle 总则

The holder of a Manufacturing Authorisation must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorisation and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company?s suppliers and by the distributors. To achieve the quality objective reliably there must be a comprehensively designed and correctly implemented system of Quality Assurance incorporating Good Manufacturing Practice, Quality Control and Quality Risk Management. It should be fully documented and its effectiveness monitored. All parts of the Quality Assurance system should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the holder of the Manufacturing Authorisation and for the Qualified Person(s). 生产许可持有人必须确保生产的药品适合预期用途，符合上市许可要求，不能由于安全性，质量或有效性不足而对患者产生风险。实现这个质量目标是高层管理者的职责，同时也需要公司内部各个层次，各部门员工，以及公司的供应商，销售企业共同参与并承担义务。为了可靠地达到这个质量目标，必须拥有一个经过综合设计，并且正确实施的质量保证系统，整合药品生产质量管理规范，质量控制与质量风险管理。该系统应当具备充分的证明文件并对其有效性进行监控。质量保证体系的所有部分都应配备胜任人员，合适和足够的厂房，设备与设施。对于生产许可持有人与质量授权人还有额外法律责任。

The basic concepts of Quality Assurance, Good Manufacturing Practice，Quality Control and Quality Risk Management are inter-related. They are described here in order to emphasise their relationships and their fundamental importance to the production and control of medicinal products.

质量保证，药品生产质量管理规范，质量控制与质量风险管理的基本概念是相互关联的。这里的描述是为了强调其相互关系以及对于药品生产与控制的重要性。

第一章Quality Assurance质量保证

1.1 Quality Assurance is a wide-ranging concept, which covers all matters, which individually or collectively influence the quality of a product. It is the sum total of the organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use. Quality Assurance therefore incorporates Good Manufacturing Practice plus other factors outside the scope of this Guide.

质量保证是一个广义的概念，其涵盖了单独或集合的影响产品质量的所有因素。质量保证是所有为了确保药品达到预期用途所要求的质量所做的组织和安排的总和。质量保证整合了药品生产质量管理规范以及本指南以外的其它方面。

The system of Quality Assurance appropriate for the manufacture of medicinal products should ensure that:

适用于药品生产的质量保证体系应确保以下方面：

(i) medicinal products are designed and developed in a way that takes account of the requirements of Good Manufacturing Practice;

药品的设计与开发需考虑到GMP 的要求;

(ii) production and control operations are clearly specified and Good Manufacturing Practice adopted;

明确规定生产和控制操作，应用GMP;

(iii) managerial responsibilities are clearly specified;

明确规定管理职责;

(iv) arrangements are made for the manufacture，supply and use of the correct starting and packaging materials; 安排生产，为供应和使用正确的起始原料与包装材料制定计划;

(v) all necessary controls on intermediate products，and any other in-process controls and validations are carried out;

实施所有对中间产品必要的控制，以及其它中间控制和验证;

(vi) the finished product is correctly processed and checked，according to the defined procedures;

按照制定的程序对成品进行正确加工和检查;

(vii) medicinal products are not sold or supplied before a Qualified Person has certified that each production batch has been produced and controlled in accordance with the requirements of the Marketing Authorisation and any other regulations relevant to the production，control and release of medicinal products;

在质量授权人确认每批产品的生产与控制符合上市许可要求以及药品生产，控制和放行相关的规定之前，不得销售或供应该药品;

(viii) satisfactory arrangements exist to ensure，as far as possible，that the medicinal products are stored，distributed and subsequently handled so that quality is maintained throughout their shelf life;

应尽可能通过完善的安排来保证药品的贮存，分发和随后的处理使药品在其整个生命周期都保持原有质量; (ix) there is a procedure for Self-Inspection and/or quality audit，which regularly appraises the effectiveness and applicability of the Quality Assurance system.

有一个自检和/或质量审计程序，定期评估质量保证体系的有效性和适用性。

Good Manufacturing Practice for Medicinal Products (GMP) 药品生产质量管理规范(GMP) 1.2 Good Manufacturing Practice is that part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the Marketing Authorisation or product specification.

GMP 是质量保证的一个部分，其保证始终如一地生产及控制产品，使其质量符合产品的预期用途以及上市许可要求或产品质量标准。

Good Manufacturing Practice is concerned with both production and quality control.

GMP 涉及到生产和质量控制。

The basic requirements of GMP are that:

GMP 的基本要求如下

(i) all manufacturing processes are clearly defined，systematically reviewed in the light of experience and shown to be capable of consistently manufacturing medicinal products of the required quality and complying with their specifications;

所有的生产工艺都经过明确并根据经验进行了系统地审核，能够始终如一地生产要求质量的产品并符合其质量标准;

(ii) critical steps of manufacturing processes and significant changes to the process are validated;

对生产工艺的关键步骤以及对工艺的重大变更实施验证;

(iii) all necessary facilities for GMP are provided including:

?appropriately qualified and trained personnel;

?adequate premises and space;

?suitable equipment and services;

?correct materials，containers and labels;

?approved procedures and instructions;

?suitable storage and transport;

提供所有GMP 必须的设施，其中包括:

?有适当资质并经过培训的员工;

?充足的厂房与空间;

?合适的设备与辅机;

?正确的物料，容器和标签;

?批准的规程及指令;

?适合的贮存与运输;

(iv) instructions and procedures are written in an instructional form in clear and unambiguous language，specifically applicable to the facilities provided;

指令与规程的编写应当用明确和清楚的语言表达，采用确定的格式，尤其专属设施的指令和规程;

(v) operators are trained to carry out procedures correctly;

对操作人员进行培训，使其能正确地执行规程;

(vi) records are made, manually and/or by recording instruments, during manufacture which demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the product was as expected. Any significant deviations are fully recorded and investigated;

在生产过程中人工记/或由仪器进行的记录能够证明所有步骤是确实按照预定的程序和指令的要求执行，也证明产品的质量和数量达到预期要求。所有重大的偏差必须完整记录并进行调查;

(vii) records of manufacture including distribution which enable the complete history of a batch to be traced, are retained in a comprehensible and accessible form;

生产包括销售的记录应能够追踪整批的生产历史，这些记录要完整，并以可读取方式进行保存;

(viii) the distribution (wholesaling) of the products minimises any risk to their quality;

产品销售(批发)应对质量的风险进行最小化;

(ix) a system is available to recall any batch of product, from sale or supply;

应有一个系统能够从销售或供应召回任何批产品;

(x) complaints about marketed products are examined, the causes of quality defects investigated and appropriate measures taken in respect of the defective products and to prevent reoccurrence.

对上市产品的投诉进行核查，调查质量缺陷的原因，对缺陷产品采取适当措施，并防止再次发生。

Quality Control质量控制

1.3 Quality Control is that part of Good Manufacturing Practice which is concerned with sampling, specifications and testing, and with the organisation, documentation and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory.

质量控制是GMP 的一部分，其涉及取样，规格标准，检验以及组织机构，文件管理和放行规程，这些都是保证所有必需的和相关的检验确实实施，也确保对于未对质量进行判定之前，物料不能放行使用，成品也不能放行销售。

The basic requirements of Quality Control are that: 质量控制的基本要求如下:

(i) adequate facilities, trained personnel and approved procedures are available for sampling, inspecting and testing starting materials, packaging materials, intermediate, bulk, and finished products, and where appropriate for monitoring environmental conditions for GMP purposes;

为了对起始物料，包装材料，中间体，半成品与成品进行取样，检查和检验，应有充足设施，经过培训的人员及已批准的程序，如果适用的话，为了符合GMP对环境条件实施监控。

(ii) samples of starting materials, packaging materials, intermediate products, bulk products and finished products are taken by personnel and by methods approved by Quality Control;

起始物料，包装材料，中间产品，半成品，成品的取样应由质量控制部门批准的人员，采用已批准方法进行;

(iii) test methods are validated;

检验方法必须是通过验证;

(iv) records are made, manually and/or by recording instruments, which demonstrate that all the required sampling, inspecting and testing procedures were actually carried out. Any deviations are fully recorded and investigated;

进行记录，可手工和/或由仪器记录，以证明所有要求取样以及测试程序都实际实施。所有偏差已经完整记录并进行调查;

(v) the finished products contain active ingredients complying with the qualitative and quantitative composition of the Marketing Authorisation, are of the purity required, and are enclosed within their proper containers and correctly labelled;

成品含有的原料药，与市场注册的定性和定量要求相一致，纯度符合要求，贮存在正确的容器中，并贴上正确的标签;

(vi) records are made of the results of inspection and that testing of materials, intermediate, bulk, and finished products is formally assessed against specification. Product assessment includes a review and evaluation of relevant production documentation and an assessment of deviations from specified procedures;

检查结果需要进行记录，对照质量标准对物料，中间产品，半成品对成品进行正式评估检查的结果也要进行记录。对产品评估包括对相关的生产文件进行审核与评价，以及偏离特定规程的偏差的评估。

(vii) no batch of product is released for sale or supply prior to certification by a Qualified Person that it is in accordance with the requirements of the relevant authorisations;

任何批次的产品在质量授权人确认符合相关许可的标准之前均不能放行或销售。

(viii) sufficient reference samples of starting materials and products are retained to permit future examination of the product if necessary and that the product is retained in its final pack unless exceptionally large packs are produced.

起始物料与成品需保留足够参比样品，以备将来有需要的时候进行检验，成品按最终包装留样，大包装除外。

Product Quality Review产品质量审核

1.4 Regular periodic or rolling quality reviews of all licensed medicinal products, including export only products, should be conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product to highlight any trends and to identify

product and process improvements. Such reviews should normally be conducted and documented annually, taking into account previous reviews, and should include at least:

应当对所有许可的医药产品，包括仅供出口的产品，进行定期或轮换的质量审核，应当客观地核实与现行工艺一致性，以及起始物料与成品的规格标准的恰当性，着重突出所有趋势，确定产品与工艺改进。这样的审核通常应该每年都进行，并有文件记录，还应将先前的审核考虑在内，至少应包括:

(i) A review of starting materials including packaging materials used in the product, especially those from new sources.

审核用于产品的起始原料包括包装材料，特别是来自新来源;

(ii) A review of critical in-process controls and finished product results.

审核关键中间控制及成品结果;

(iii) A review of all batches that failed to meet established specification(s) and their investigation.

审核所有不符合已制定的质量标准的批次并对其进行调查;

(iv) A review of all significant deviations or non-conformances, their related investigations, and the effectiveness of resultant corrective and preventative actions taken.

审核所有重大偏差或不符合项，及其相关调查，所采取的纠正预防措施的有效性;

(v) A review of all changes carried out to the processes or analytical methods.

审核工艺或分析方法的所有变更;

(vi) A review of Marketing Authorisation variations submitted/granted/refused, including those for third country (export only) dossiers.

审核上市许可变更的申报/批准/退审，包括第三国(仅仅出口)上市许可变更档案;

(vii) A review of the results of the stability monitoring programme and any adverse trends.

审核稳定性监测程序的结果及任何不良趋势;

(viii) A review of all quality-related returns, complaints and recalls and the investigations performed at the time.

审核所有因质量相关的退货，投诉，召回及当时实施的调查;

(ix) A review of adequacy of any other previous product process or equipment corrective actions.

审核其它以往产品工艺或设备的纠正措施充足性;

(x) For new marketing authorisations and variations to marketing authorisations, a review of post-marketing commitments.

对于新上市许可与上市变更，审核上市后状况;

(xi) The qualification status of relevant equipment and utilities, e.g. HV AC, water, compressed gases, etc.

相关设备和设施，如空调净化系统，水系统，压缩空气等的确认状态;

(xii) A review of any contractual arrangements as defined in Chapter 7 to ensure that they are up to date.

审核技术协议确保其更新。

The manufacturer and marketing authorisation holder should evaluate the results of this review, where different,

and an assessment made of whether corrective and preventative action or any revalidation should be undertaken. Reasons for such corrective actions should be documented. Agreed corrective and preventative actions should be completed in a timely and effective manner. There should be management procedures for the ongoing management and review of these actions and the effectiveness of these procedures verified during selfinspection. Quality reviews may be grouped by product type, e.g. solid dosage forms, liquid dosage forms, sterile products, etc. where scientifically justified. Where the marketing authorisation holder is not the manufacturer, there should be a technical agreement in place between the various parties that defines their respective responsibilities in producing the quality review. The Qualified Person responsible for final batch certification together with the marketing authorisation holder should ensure that the quality review is performed in a timely manner and is accurate.

如果生产企业与上市注册持有人不同应该评价该审核结果，并评估是否做出纠正预防措施，或应当进行再验证。纠正措施的原因要存档。决定的纠正预防措施就要及时有效完成。应有用于正在实施的管理与审核的管理规程，自检过程中，核实这些程序的有效性。如果有科学依据，质量审核可按产品类型分类，如固体制剂，液体制剂与无菌产品等。

如上市许可持有人不是制造企业，则各方之间应有技术协议书，规定在生产中质量审核中各方责任。质量授权人与上市许可持有人共同负责最终产品认可，应确保质量审核及时并正确实施。

Quality Risk Management质量风险管理

1.5 Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product. It can be applied both proactively and retrospectively.

质量风险管理是对药品整个生命周期进行质量风险的评估、控制、沟通、回顾的系统过程,运用时可采用前瞻或回顾的方式。

1.6 The quality risk management system should ensure that:

- the evaluation of the risk to quality is based on scientific knowledge, experience with the process and ultimately links to the protection of the patient

- the level of effort, formality and documentation of the quality risk management process is commensurate with the level of risk

Examples of the processes and applications of quality risk management can be found inter alia in Annex 20.

质量风险管理系统应当保证:

–基于对工艺的科学知识和经验以评价质量风险，并最终联系到对患者的保护。

–质量风险管理应与存在风险的级别相适应，确定相应的方法、措施、形式和文件。质量风险管理的过程与应用举例可在附件20 中找到。

第二章:员工

Principle原则

The establishment and maintenance of a satisfactory system of quality assurance and the correct manufacture of medicinal products relies upon people. For this reason there must be sufficient qualified personnel to carry out all the tasks which are the responsibility of the manufacturer. Individual responsibilities should be clearly understood by the individuals and recorded. All personnel should be aware of the principles of Good Manufacturing Practice that affect them and receive initial and continuing training, including hygiene instructions, relevant to their needs. 建立一个令人满意质量保证体系，并维持该系统，以及药品的正确生产都仰赖于人员。因此，必需有资质的人员来实施生产企业所负责的任务。应明确规定每个部门和每个岗位的职责，所有人员应明确并理解自己的职责，所有人员都必须意识到与自己相关的GMP 原则，并且根据他们的需要接受上岗培训与继续培

训，其包括人员卫生指导。

General总论

2.1 The manufacturer should have an adequate number of personnel with the necessary qualifications and practical experience. The responsibilities placed on any one individual should not be so extensive as to present any risk to quality.

制造企业应当有足够数量的具备所需资质及实践经验的员工。每个人所承担的职责不应过多，以免导致质量风险。

2.2 The manufacturer must have an organisation chart. People in responsible positions should have specific duties recorded in written job descriptions and adequate authority to carry out their responsibilities. Their duties may be delegated to designated deputies of a satisfactory qualification level. There should be no gaps or unexplained overlaps in the responsibilities of those personnel concerned with the application of Good Manufacturing Practice. 生产企业必须有一张组织机构图。不同岗位的人员均应有详细的书面工作职责，并有相应的职权。其职责可担当适当资质水平的任职。与GMP 实施相关的人员岗位职责不得有空缺，重叠的职责应有明确的解释。

Key Personnel关键人员

2.3 Key Personnel include the head of Production, the head of Quality Control, and if at least one of these persons is not responsible for the duties described in Article 51 of Directive 2001/83/EC1, the Qualified Person(s) designated for the purpose. Normally key posts should be occupied by full-time personnel. The heads of Production and Quality Control must be independent from each other. In large organisations, it may be necessary to delegate some of the functions listed in 2.5, 2.6 and 2.7.

关键人员包括生产部门和质量控制部门负责人，如果他们中没有一人来担负2001/83/EC1号法令第51 条中的责任，就要另外指定质量授权人来负责。通常关键岗位应该由全职人员担任。生产部门与质量控制部门负责人必须互相独立。在一个大的组织中，有必要对第2.5， 2.6和2.7节中所列的职责进行授权。

2.4 The duties of the Qualified Person(s) are fully described in Article 51 of Directive 2001/83/EC, and can be summarised as follows:

a) for medicinal products manufactured within the European Community, a Qualified Person must ensure that each batch has been produced and tested/checked in accordance with the directives and the marketing authorisation (2);

(b) for medicinal products manufactured outside the European Community, a Qualified Person must ensure that each imported batch has undergone, in the importing country, the testing specified in paragraph 1 (b) of Article 51;

(c) a Qualified Person must certify in a register or equivalent document, as operations are carried out and before any release, that each production batch satisfies the provisions of Article 51.

The persons responsible for these duties must meet the qualification requirements laid down in Article 493 of the same Directive, they shall be permanently and continuously at the disposal of the holder of the Manufacturing Authorisation to carry out their responsibilities. Their responsibilities may be delegated, but only to other Qualified Person(s).

质量授权人的职责在2001/83/EC 法令的第51 条中已有详细描述，现概述如下:

(a) 对于在欧盟内制造的药品，质量授权人必须确保每批药品已经按照法令及上市许可2进行生产，测试/检查;

(b) 对于在欧盟以外制造的药品，质量授权人须确保每批进口的批次在进口国家按第51 条第1(b)段所规定进行了检测;

51 条中规定。

承担该职责人员必须符合相同法令第493条中所规定的资质要求，他们应当永久并持续地接受上市许可持有人安排以履行其职责。其职责可以委托，但只能委托给其他的质量授权人。

2.5 The head of the Production Department generally has the following responsibilities:

i. to ensure that products are produced and stored according to the appropriate documentation in order to obtain the required quality;

ii. to approve the instructions relating to production operations and to ensure their strict implementation;

iii. to ensure that the production records are evaluated and signed by an authorised person before they are sent to the Quality Control Department;

iv. to check the maintenance of his department, premises and equipment;

v. to ensure that the appropriate validations are done;

vi. to ensure that the required initial and continuing training of his department personnel is carried out and adapted according to need.

生产部门负责人通常有以下职责:

i 为了达到质量要求，确保产品按照相关文件规定生产和储存;

ii 批准与生产操作相关指示，并确保其被严格实施;

iii 确保生产记录在送到质量控制部门之前要经过授权人员评估和签字;

iv 核实本部门厂房和设备维护;

v 确保实施了适当的验证;

vi 确保对本部门人员实施了所需要的最初与持续培训。

2.6 The head of the Quality Control Department generally has the following responsibilities:

i. to approve or reject，as he sees fit, starting materials, packaging materials, and intermediate, bulk and finished products;

ii. to evaluate batch records;

iii. to ensure that all necessary testing is carried out;

iv. to approve specifications, sampling instructions, test methods and other Quality Control procedures;

v. to approve and monitor any contract analysts;

vi. to check the maintenance of his department, premises and equipment;

vii. to ensure that the appropriate validations are done;

viii. to ensure that the required initial and continuing training of his department personnel is carried out and adapted according to need.

Other duties of the Quality Control Department are summarised in Chapter 6.

质量控制部门负责人通常有以下职责:

i 如果其认为合适，批准或拒绝起始物料，包装材料，中间体，半成品与成品;

Ii 评价批记录;

iii 确保实施了所有必需的检验;

iv 批准规格标准，取样指示，检验方法以及其它质量控制程序;

v 批准和监督任何合同分析企业;

vi 核实本部门厂房和设备维护;

vii 确保实施了适当验证;

viii 确保对本部门人员实施了所需要的最初与持续培训。质量控制部门的其它职责见第六章。

2.7 The heads of Production and Quality Control generally have some shared，or jointly exercised，responsibilities relating to quality. These may include, subject to any national regulations:

—the authorisation of written procedures and other documents, including amendments;

—the monitoring and control of the manufacturing environment;

—plant hygiene;

—process validation;

—training;

—the approval and monitoring of suppliers of materials;

—the approval and monitoring of contract manufacturers;

—the designation and monitoring of storage conditions for materials and products;

—the retention of records;

—the monitoring of compliance with the requirements of Good Manufacturing Practice;

—the inspection, investigation, and taking of samples, in order to monitor factors which may affect product quality.

生产部门与质量控制部门负责人在质量的责任方面也有一些共享或交叉。其可能包括，并取决于国家的所有规定:

—- 书面程序与其它文件，包括修订文件的授权;

—- 生产的监测与控制;

—- 车间卫生;

—- 工艺验证;

—- 培训;

—- 批准和监测物料供应企业;

—- 批准和监测合同生产企业;

—- 指定与监控物料与产品储存条件;

—- 保存记录;

—- 监测与GMP 要求一致性;

—- 为监测可能影响产品质量因素进行检查，调查和取样。

Training 培训

2.8 The manufacturer should provide training for all the personnel whose duties take them into production areas or into control laboratories (including the technical，maintenance and cleaning personnel), and for other personnel whose activities could affect the quality of the product.

生产企业应对所有因工作需要进入生产区或质量控制实验室人员(包括技术, 维护和清洁人员)，以及其活动可能影响产品质量的其它人员实施培训。

2.9 Besides the basic training on the theory and practice of Good Manufacturing Practice, newly recruited personnel should receive training appropriate to the duties assigned to them. Continuing training should also be given, and its practical effectiveness should be periodically assessed. Training programmes should be available, approved by either the head of Production or the head of Quality Control, as appropriate. Training records should be kept.

除了基本的GMP 理论与实践的培训，新员工还要接受与分派给其职责相关的培训。同样应当实施持续培训，并且应当定期地评估培训实际效果。培训计划要切实可行，如果可能，要得到生产部门负责人或质量控制部门负责人的批准。应当保存培训记录。

2.10 Personnel working in areas where contamination is a hazard, e.g. clean areas or areas where highly active, toxic, infectious or sensitising materials are handled, should be given specific training.

有些区域，如清洁区或处理高生物活性，毒性，感染性或高致敏性物料等若被污染很危险的区域，在那里工作的人员应该经过专门的培训。

2.11 Visitors or untrained personnel should，preferably, not be taken into the production and quality control areas. If this is unavoidable, they should be given information in advance, particularly about personal hygiene and the prescribed protective clothing. They should be closely supervised.

最好不要把参观者或未经培训的人员带到生产或质量控制区。如果这种情况不可避免，要先告知，特别是个人卫生和工作服的详细情况。而且对他们要进行严密监督。

2.12 The concept of Quality Assurance and all the measures capable of improving its understanding and implementation should be fully discussed during the training sessions.

在培训中，应对质量保证的概念，及所有有利于理解和执行质量保证的措施进行充分讨论。

Personnel Hygiene个人卫生

2.13 Detailed hygiene programmes should be established and adapted to the different needs within the factory. They should include procedures relating to the health, hygiene practices and clothing of personnel. These procedures should be understood and followed in a very strict way by every person whose duties take him into the production and control areas. Hygiene programmes should be promoted by management and widely discussed during training sessions.

工厂应制定详细的卫生程序并适应工厂不同的需要。其包括与个人的健康，卫生习惯，着装相关的程序。在生产区和控制区工作的人员应当理解并严格遵守这些程序。卫生规程应由管理人员改进，并在培训时进行充分讨论。

2.14 All personnel should receive medical examination upon recruitment. It must be the manufacturer?s responsibility that there are instructions ensuring that health conditions that can be of relevance to the quality of products come to the manufacturer?s knowledge. After the first medical examination, examinations should be carried out when necessary for the work and personal health.

所有新招聘人员要经过体检。生产企业应该有指南说明来保证与产品质量相关的生产，健康状态作为生产的知识，这应该是生产企业的职责。初次体检后，在员工的工作或健康状况有必要时，应重新进行体检。

2.15 Steps should be taken to ensure as far as is practicable that no person affected by an infectious disease or having open lesions on the exposed surface of the body is engaged in the manufacture of medicinal products.

采取可行的措施来保证无传染病患者和体表有伤口者从事药品生产。

2.16 Every person entering the manufacturing areas should wear protective garments appropriate to the operations to be carried out.

进入制造区的任何人员应该穿着其操作相应防护服。

2.17 Eating, drinking, chewing or smoking, or the storage of food, drink, smoking materials or personal medication in the production and storage areas should be prohibited. In general, any unhygienic practice within the manufacturing areas or in any other area where the product might be adversely affected, should be forbidden.禁止在生产与储存区吃东西，喝水，咀嚼或吸烟，储存食物，饮料，香烟或个人服用的药品。总之，杜绝在生产区内或其它可能影响药品质量区域内的所有不卫生行为。

2.18 Direct contact should be avoided between the operator?s hands and the exposed product as well as with any part of the equipment that comes into contact with the products.

应当避免操作人员的裸手接触药品以及与药品相接触的设备表面。

2.19 Personnel should be instructed to use the hand-washing facilities.

应指导员工使用洗手设施。

2.20 Any specific requirements for the manufacture of special groups of products, for example sterile preparations, are covered in the annexes.

不同类别药品的所有具体生产要求参见附录，如无菌药品。

第三章厂房设备

3.1Premises should be situated in an environment which, when considered together with measures to protect the manufacture, presents minimal risk of causing contamination of materials or products.

应根据厂房及制造保护措施综合考虑选址问题，厂房所处的环境应能使物料或产品遭受污染的风险最小。

3.2 Premises should be carefully maintained, ensuring that repair and maintenance operations do not present any hazard to the quality of products. They should be cleaned and, where applicable, disinfected according to detailed written procedures.

厂房应仔细维护，应确保维修活动无影响产品的质量危险。厂房应按详细的书面规程进行清洁，如果需要，应进行消毒。

3.3 Lighting, temperature, humidity and ventilation should be appropriate and such that they do not adversely affect, directly or indirectly, either the medicinal products during their manufacture and storage, or the accurate functioning of equipment.

厂房应有适当的照明，温湿度与通风，并确保在制造与贮存期间药品质量以及相关设备的性能不直接或间接地受其不良影响。

3.4 Premises should be designed and equipped so as to afford maximum protection against the entry of insects or other animals.

厂房的设计并装备应能最大程度防止昆虫或其它动物的进入。

3.5 Steps should be taken in order to prevent the entry of unauthorised people. Production, storage and quality control areas should not be used as a right of way by personnel who do not work in them.

应采取适当措施，防止未经批准的人员进入。生产，贮存和质量控制区不应作为非本区工作人员的通道。

3.6 In order to minimise the risk of a serious medical hazard due to cross-contamination, dedicated and self contained facilities must be available for the production of particular medicinal products, such as highly sensitising materials (e.g. penicillins) or biological preparations (e.g. from live micro-organisms). The production of certain additional products, such as certain antibiotics, certain hormones, certain cytotoxics, certain highly active drugs and non-medicinal products should not be conducted in the same facilities. For those products, in exceptional cases, the principle of campaign working in the same facilities can be accepted provided that specific precautions are taken and the necessary validations are made. The manufacture of technical poisons, such as pesticides and herbicides, should not be allowed in premises used for the manufacture of medicinal products.

为降低由交叉污染所致严重医学危害风险，一些特殊药品，如高敏感药品(如，青霉素类)或生物制剂(如，活性微生物类)必须采用专用和独立的生产设施。某些抗生素，激素，细胞毒素，高活性药物类产品，与非药品不应在同一生产设施进行生产。对于这些产品，在特殊情况下，如采取特别防护措施并经过必要的验证，不同产品共用同一生产设施是可以接受的。药品制造厂房不得用于如杀虫剂和除草剂等工业毒性物品的制造。

3.7 Premises should preferably be laid out in such a way as to allow the production to take place in areas connected in a logical order corresponding to the sequence of the operations and to the requisite cleanliness levels. 厂房应当最好按生产工艺流程及相应洁净级别要求合理布局。

3.8 The adequacy of the working and in-process storage space should permit the orderly and logical positioning of equipment and materials so as to minimise the risk of confusion between different medicinal products or their components, to avoid cross-contamination and to minimise the risk of omission or wrong application of any of the manufacturing or control steps.

工作区和中间物料存贮区应有足够的空间,以有序地存放设备和物料，避免不同药品或组分混淆，避免交叉污染，避免制造或质量控制操作发生遗漏或差错。

3.9 Where starting and primary packaging materials, intermediate or bulk products are exposed to the environment, interior surfaces (walls, floors and ceilings) should be smooth, free from cracks and open joints, and should not shed particulate matter and should permit easy and effective cleaning and, if necessary, disinfection.

起始物料，内包装材料，中间体或半成品暴露环境的内表面(墙壁，地面，天棚)应当平整光滑，无裂缝，接口严密，无颗粒物脱落，便于有效清洁和必要时进行消毒。

3.10 Pipework，light fittings, ventilation points and other services should be designed and sited to avoid the creation of recesses which are difficult to clean. As far as possible, for maintenance purposes, they should be accessible from outside the manufacturing areas.

管道，照明设施，送风口和其它公用设施的设计和安装应避免出现难以清洁的凹陷部位。应尽可能做到在制造区外部对它们进行维护。

3.11 Drains should be of adequate size, and have trapped gullies. Open channels should be avoided where possible, but if necessary, they should be shallow to facilitate cleaning and disinfection.

排水设施应大小适宜，安装防止倒灌的装置。应尽可能避免明沟，不可避免时，明沟宜浅，以方便清洁和消毒。

3.12 Production areas should be effectively ventilated, with air control facilities (including temperature and, where necessary, humidity and filtration) appropriate both to the products handled, to the operations undertaken within them and to the external environment.

应根据处理的产品，生产操作要求及外部环境状况配置空调净化系统，使生产区有效的通风(包括温度控制，必要的湿度控制和空气净化过滤)。

3.13 Weighing of starting materials usually should be carried out in a separate weighing room designed for that use.

起始物料的称量通常应在专门设计的称量室内进行。

3.14 In cases where dust is generated (e.g. during sampling, weighing, mixing and processing operations, packaging of dry products), specific provisions should be taken to avoid crosscontamination and facilitate cleaning.

在产尘区域(如，取样，称量，混合与加工，干燥产品包装)，应采取专门的措施避免交叉污染并便于清洁。

3.15 Premises for the packaging of medicinal products should be specifically designed and laid out so as to avoid mix-ups or cross-contamination.

用于药品包装的厂房应专门设计和布局，以避免混淆或交叉污染。

3.16 Production areas should be well lit, particularly where visual on-line controls are carried out.

生产区应有足够的照明，特别是产品在线目检区。

3.17 In-process controls may be carried out within the production area provided they do not

carry any risk for the production.

在生产区区域内可进行中间控制，但不得给生产带来风险。

3.18 Storage areas should be of sufficient capacity to allow orderly storage of the various categories of materials and products: starting and packaging materials, intermediate, bulk and finished products, products in quarantine, released, rejected, returned or recalled.

储存区应有足够的空间，以便有序地存放各类物料和产品:起始物料，包装材料，中间体，半成品与成品，以及待检，合格，不合格，退回或召回的产品等。

3.19 Storage areas should be designed or adapted to ensure good storage conditions. In particular, they should be clean and dry and maintained within acceptable temperature limits. Where special storage conditions are required (e.g. temperature, humidity) these should be provided, checked and monitored.

储存区的设计或建造应确保良好的储存条件。应特别的是其应当清洁并干燥，而且保持温度接受制限度内。如需要特殊贮存条件(如温，湿度)时，应予满足，并进行核实与监测。

3.20 Receiving and dispatch bays should protect materials and products from the weather. Reception areas should be designed and equipped to allow containers of incoming materials to be cleaned where necessary before storage. 收发与发放区应能保护物料与产品免受外界气候的影响。接收区的设计和装备配置应确保进货的物料容器在进入储存前可进行必要的清洁。

3.21 Where quarantine status is ensured by storage in separate areas, these areas must be clearly marked and their access restricted to authorised personnel. Any system replacing the physical quarantine should give equivalent security.

当用隔离区域保证待检状态，其应有醒目标识，且只限于经批准的人员出入。如果采用其它方法替代物理待检，应具有同等的安全性。

3.22 There should normally be a separate sampling area for starting materials. If sampling is performed in the storage area, it should be conducted in such a way as to prevent contamination or cross-contamination.

通常应有隔离的起始物料取样区。如在储存区取样,则应以能防止污染或交叉污染的方式进行。

3.23 Segregated areas should be provided for the storage of rejected, recalled or returned materials or products.

不合格，退回或召回的物料或产品应隔离存放。

3.24 Highly active materials or products should be stored in safe and secure areas.

高活性物料或产品应存放在安全的区域内。

3.25 Printed packaging materials are considered critical to the conformity of the medicinal product and special attention should be paid to the safe and secure storage of these materials.

印刷好的包装材料是确保药品标识正确的关键，应特别注意安全贮存。

3.26 Normally, Quality Control laboratories should be separated from production areas. This is particularly important for laboratories for the control of biologicals, microbiologicals and radioisotopes, which should also be

separated from each other.

质量控制实验室通常应与生产区隔离。这一点对于生物，微生物和放射性同位素控制实验室非常重要，其还应彼此分开。

3.27 Control laboratories should be designed to suit the operations to be carried out in them. Sufficient space should be given to avoid mix-ups and cross-contamination. There should be adequate suitable storage space for samples and records.

实验室设计应确保其适用于预期的操作。实验室应有足够的空间以避免混淆和交叉污染，同时应有足够的适合样品和记录保存空间。

3.28 Separate rooms may be necessary to protect sensitive instruments from vibration, electrical interference, humidity, etc.

必要时，应设置专门的仪器室，使高灵敏仪器免受电压震动，电磁，潮湿等因素的干扰。

3.29 Special requirements are needed in laboratories handling particular substances, such as biological or radioactive samples.

在实验室中处理特殊物质的特殊要求，如生物或放射性样品。

3.30 Rest and refreshment rooms should be separate from other areas.

休息室/餐饮室应与其它区域分开。

3.31 Facilities for changing clothes, and for washing and toilet purposes should be easily accessible and appropriate for the number of users. Toilets should not directly communicate with production or storage areas.

更衣室，盥洗室与卫生间应方便人员出入，并与使用人数相适应。卫生间不得与生产区或储存区直接相连。

3.32 Maintenance workshops should as far as possible be separated from production areas Whenever parts and tools are stored in the production area, they should be kept in rooms or lockers reserved for that use.

维修间应尽可能与生产区分开。存放在生产区内的维修用备件与工具，应放置在专门的房间或上锁的工具柜中。

3.33 Animal houses should be well isolated from other areas, with separate entrance (animal access) and air handling facilities.

动物房应与其它区域严格分开，并设有专门(动物)的通道以及空气处理设施。

Equipment设备

3.34 Manufacturing equipment should be designed, located and maintained to suit its intended purpose.

生产设备的设计，选址，维护应适用于预定用途。

3.35 Repair and maintenance operations should not present any hazard to the quality of the products.

设备的维修和维护操作不应危害产品质量。

3.36 Manufacturing equipment should be designed so that it can be easily and thoroughly cleaned. It should be cleaned according to detailed and written procedures and stored only in a clean and dry condition.

生产设备的设计应便于彻底清洁。应按书面的详细规程清洁设备，并在清洁，干燥的条件下存放。

3.37 Washing and cleaning equipment should be chosen and used in order not to be a source of contamination.

对于清洗，清洁设备的选择和使用，应注意避免其成为污染源。

3.38 Equipment should be installed in such a way as to prevent any risk of error or of contamination.

设备的安装方式应有利于避免出现任何差错或污染的风险。

3.39 Production equipment should not present any hazard to the products. The parts of the production equipment that come into contact with the product must not be reactive, additive or absorptive to such an extent that it will affect the quality of the product and thus present any hazard.

生产设备不应对产品有任何危害。与产品接触的部件必须与药品不发生化学反应，不能填加或吸附物质而影响产品质量,进而造成任何危害。

3.40 Balances and measuring equipment of an appropriate range and precision should be available for production and control operations.

用于药品的生产和控制的衡器和量具应具有适当量程和精密度。

3.41 Measuring，weighing, recording and control equipment should be calibrated and checked at defined intervals by appropriate methods. Adequate records of such tests should be maintained.

应按照适当的方法定期对测量，称重，记录和控制设备进行校准与核查，并保存相关记录。

3.42 Fixed pipework should be clearly labelled to indicate the contents and，where applicable, the direction of flow.

安装的管线应清楚地标明其内容物,必要时，还应标明流向。

3.43 Distilled, deionized and, where appropriate, other water pipes should be sanitised according to written procedures that detail the action limits for microbiological contamination and the measures to be taken.

应按照书面规程消毒蒸馏水，去离子水管道，以及其它供水管路(必要时)，书面规程中应详细规定微生物污染的行动限及应采取的措施。

3.44 Defective equipment should, if possible, be removed from production and quality control areas, or at least be clearly labelled as defective.

可能时，应将有故障的设备搬出生产和质量控制区，或至少应贴上醒目的标识。

第四章文件

Principle

Good documentation constitutes an essential part of the quality assurance system and is key to operating in compliance with GMP requirements. The various types of documents and media used should be fully defined in the manufacturer's Quality Management System. Documentation may exist in a variety of forms, including paper-based, electronic or photographic media. The main objective of the system of documentation utilized must be to establish, control, monitor and record all activities which directly or indirectly impact on all aspects of the quality of medicinal products. The Quality Management System should include sufficient instructional detail to facilitate a common understanding of the requirements, in addition to providing for sufficient recording of the various processes and evaluation of any observations, so that ongoing application of the requirements may be demonstrated.

There are two primary types of documentation used to manage and record GMP compliance: instructions

(directions, requirements) and records/reports. Appropriate good documentation practice should be applied with respect to the type of document.

Suitable controls should be implemented to ensure the accuracy, integrity, availability and legibility of documents. Instruction documents should be free from errors and available in writing. The term …written? means recorded, or documented on media from which data may be rendered in a human readable form.

良好的文件管理是质量保证系统的重要组成部分也是符合GMP要求的，各种类型的文件和储存形式在生产厂家的质量管理系统中都应该有完整的定义。文件管理可以各种形式存在，包括纸版，电子版和影像版。文件管理系统最主要的目标是能够对药品的质量有间接或直接影响到所有方面进行记录控制和监督。质量管理系统应该包含完整的理解便于对要求的一般理解，也为了对各种过程进行充分地记录和所有观察结果的评估，以表明这些要求是持续适用的。

这里有两种基本的文件类型用于管理和记录GMP符合性：指令（指示，要求）和记录/报告。针对文件的类型，应该采用适当的文件管理操作实施适当的控制来保证文件的准确性，完整性，可获得性并清晰可读。指导文件应该没有错误并且能够书写，这里的书写是指记录或者从便于人类可读的形式的资料记入媒介。

Generation and Control of Documentation文件的生成和控制

4.1 All types of document should be defined and adhered to. The requirements apply

equally to all forms of document media types. Complex systems need to be understood, well documented, validated, and adequate controls should be in place. Many documents (instructions and/or records) may exist in hybrid forms, i.e. some elements as electronic and others as paper based. Relationships and control measures for master documents, official copies, data handling and records need to be stated for both hybrid and homogenous systems. Appropriate controls for electronic documents such as templates, forms, and master documents should be implemented. Appropriate controls should be in place to ensure the integrity of the record throughout the retention period.

应该定义所有类型的文件并遵守。这些要求同样的适用于所有类型的文件媒介。复杂的系统需要进行理解，有文件记录和验证，并且应该有充分的控制。很多的文件存有混合的形式，例如有些元素是电子版，其他一些是纸板。对于混合的形式和统一形式的文件，应该对主文件，正式复印件，数据处理和记录之间的关系和控制措施进行说明。应该实施对电子文档，比如模板，表格，和主文件进行适当控制。应该采用适当的控制来保证在储存期间记录的完整性。

4.2 Documents should be designed, prepared, reviewed, and distributed with care. They should comply with the relevant parts of Product Specification Files, Manufacturing and Marketing Authorisation dossiers, as appropriate. The reproduction of working documents from master documents should not allow any error to be introduced through the reproduction process.

文件应当仔细地设计，制作，审查和发放。必须符合生产标准文件，生产和上市注册文件的相关部分。从主文件作复制为工作文件时在复制的过程中不得引入任何差错。

4.3 Documents containing instructions should be approved, signed and dated by appropriate and authorised persons. Documents should have unambiguous contents and be uniquely identifiable. The effective date should be defined.

文件要经合适授权人批准和签名，并写上日期。文件内容应该清晰，应该唯一可识别，应该标明执行日期。

4.4 Documents containing instructions should be laid out in an orderly fashion and be easy to check. The style and language of documents should fit with their intended use. Standard Operating Procedures, Work Instructions and Methods should be written in an imperative mandatory style.

包含指令的文件应该已有序的方式进行排列，应该便于检查。文件的形式和语言应该适用于他们预期的用途。标准操作规程，工作指令和方法应该以强制性的形式书写。

4.5 Documents within the Quality Management System should be regularly reviewed and kept up-to-date.

质量管理系统的文件应该定期审核并及时更新。

4.6 Documents should not be hand-written; although, where documents require the entry of data, sufficient space should be provided for such entries.

文件不应该采用手写的方式，但是有些文件需要输入数据，应该为填入数据留下足够的空间。

Good Documentation Practices文件管理操作

4.7 Handwritten entries should be made in clear, legible, indelible way.

手写输入应该做到整洁清晰，可识别。

4.8 Records should be made or completed at the time each action is taken and in such a way that all significant activities concerning the manufacture of medicinal products are traceable.

实施每一个行动的时候都应该记录。采用这样的方式所有与药品生产相关的重大行为都是可追踪的。

4.9 Any alteration made to the entry on a document should be signed and dated; the alteration should permit the reading of the original information. Where appropriate, the reason for the alteration should be recorded.

对文件上的输入作任何改动都要签姓名和日期。所做的改动应该保证原始信息可读。适当的时候更改的原因也应记录。

Retention of Documents文件的保存

4.10 It should be clearly defined which record is related to each manufacturing activity and where this record is located. Secure controls must be in place to ensure the integrity of the record throughout the retention period and validated where appropriate.

应该清楚地标明每一步生产活动相关的记录和这个记录的位置。必须实施安全控制以保证这些记录在存储过程中的完整性，适当的时候应该进行验证。

4.11 Specific requirements apply to batch documentation which must be kept for one year after expiry of the batch to which it relates or at least five years after certification of the batch by the Qualified Person, whichever is the longer. For investigational medicinal products, the batch documentation must be kept for at least five years after the completion or formal discontinuation of the last clinical trial in which the batch was used. Other requirements for retention of documentation may be described in legislation in relation to specific types of product (e.g. Advanced Therapy Medicinal Products) and specify that longer retention periods be applied to certain documents. 批记录文件适用于特定的要求，这些文件必须保存至有效期后一年，或者在有资格人员批准这批产品合格后至少五年，选用较长的一个。对于研究用药品，批记录文件必须保持到本批药品的最后一次临床实验结束或正式停止后至少五年。对于文件的保留的其他要求在于产品特定类型相关的法规中有描述（例如先进治疗产品），规定某些文件使用较长的保留期。

4.12 For other types of documentation, the retention period will depend on the business activity which the documentation supports. Critical documentation, including raw data (for example relating to validation or stability), which supports information in the Marketing Authorisation should be retained whilst the authorization remains in force. It may be considered acceptable to retire certain documentation (e.g. raw data supporting validation reports or stability reports) where the data has been superseded by a full set of new data. Justification for this should be documented and should take into account the requirements for retention of batch documentation; for example, in the case of process validation data, the accompanying raw data should be retained for a period at

least as long as the records for all batches whose release has been supported on the basis of that validation exercise.

The following section gives some examples of required documents. The quality management system should describe all documents required to ensure product quality and patient safety.

对于其它类型的文件，他们的保留期依赖于文件所支持的商业行为。关键文件，包括原始资料（比如与验证或稳定性相关的资料），这文件是支持产品上市注册的信息，只要注册仍然有效，这些文件就应该保留。对于其它类型的文件，他们的保留期依赖于文件所支持的商业行为。关键文件，包括原始资料（比如与验证或稳定性相关的资料），这文件是支持产品上市注册的信息，只要注册仍然有效，这些文件就应该保留。

Specifications质量标准

4.13 There should be appropriately authorised and dated specifications for starting and packaging materials，and finished products.

起始物料，包装材料和成品应该有经授权和注明日期的质量标准。

Specifications for starting and packaging materials起始物料和包装材料的质量标准

4.14 Specifications for starting and primary or printed packaging materials should include or provide reference to，if applicable:

a) A description of the materials, including:

- The designated name and the internal code reference;

- The reference, if any, to a pharmacopoeial monograph;

- The approved suppliers and, if reasonable, the original producer of the material;

- A specimen of printed materials;

b) Directions for sampling and testing;

c) Qualitative and quantitative requirements with acceptance limits;

d) Storage conditions and precautions;

e) The maximum period of storage before re-examination.

起始物料和初级或印刷包装材料的质量标准应该包含以下内容或作为参考，如适用：

a)物料描述，包含:

- 专属名称和内部参考代码;

- 药典各论的参考，如果有的话;

- 已批准的供应商和物料的最初生产者，如果合理的话;

- 印刷材料的样品

b) 取样和检验的指南;

c) 可接受限度的定量和定性要求;

d) 储存条件和预防措施；

e) 再检之前的最大储存期。

Specifications for intermediate and bulk products中间体和半成品质量标准

4.15 Specifications for intermediate and bulk products should be available for critical steps or if these are purchased or dispatched. The specifications should be similar to specifications for starting materials or for finished products，as appropriate.

对于关键步骤中间体和半成品都应有质量标准，如果购买或分发这些物料也应该有质量标准。如果适用的话这些质量标准应该与起始物料和成品的质量标准类似。

Specifications for finished products成品的质量标准

4.16 Specifications for finished products should include or provide reference to:

a) The designated name of the product and the code reference where applicable;

b) The formula;

c) A description of the pharmaceutical form and package details;

d) Directions for sampling and testing

e) The qualitative and quantitative requirements，with the acceptance limits;

f) The storage conditions and any special handling precautions，where applicable;

g) The shelf-life.

成品的质量标准应该包含以下内容或作为参考：

a) 产品指定名称，参考代码;

b) 分子式；

c) 剂型和包装的详细描述;

d) 取样和检验指南；

e) 可接受限度的定量和定性要求;

f) 储存条件和所有特殊处理预防措施，如果适用的话;

g) 有效期

Manufacturing Formula and Processing Instructions生产处方和加工指令

Approved, written Manufacturing Formula and Processing Instructions should exist for each product and batch size to be manufactured.

生产的每种产品和批量都应有已批准的，书面的生产处方和加工指令。

4.17 The Manufacturing Formula should include:

a) The name of the product，with a product reference code relating to its specification;

b) A description of the pharmaceutical form，strength of the product and batch size;

c) A list of all starting materials to be used，with the amount of each，described; mention should be made of any substance that may disappear in the course of processing;

d) A statement of the expected final yield with the acceptable limits，and of relevant intermediate yields，where applicable.

生产处方应该包含：

a)产品名称，依照质量标准的产品代码;

b)产品剂型，规格和批量的描述;

c)所用的所有起始物料的清单，每种物料所使用的量，应该注意所有在加工过程中消失的所有物质;

d)最终收率的可接受限度的声明，如果适用的话也包含中间体相对收率。

4.18 The Processing Instructions should include:

a) A statement of the processing location and the principal equipment to be used;

b) The methods, or reference to the methods, to be used for preparing the critical equipment (e.g. cleaning, assembling, calibrating, sterilising);

c) Checks that the equipment and work station are clear of previous products, documents or materials not required for the planned process, and that equipment is clean and suitable for use;

d) Detailed stepwise processing instructions [e.g. checks on materials, pre-treatments, sequence for adding materials, critical process parameters (time, temp etc)];

e) The instructions for any in-process controls with their limits;

f) Where necessary, the requirements for bulk storage of the products; including the container, labeling and special storage conditions where applicable;

g) Any special precautions to be observed.

加工指令应该包含：

a) 加工地点和所用主要设备的声明；

b) 关键设备的准备方法或方法参考（例如清洁，组装，校验和灭菌）

c) 检查设备和工作站应该没有上批残留的本次加工操作不需要的产品，文件或物料；检查设备室清洁的适于其用途。

d) 加工指令每一步骤的详细描述（例如物料检查，预处理，添加物料的顺序，关键加工参数（时间，温度））

e) 所有中间控制的指令和其限度；

f) 有必要的话，产品散装储存的要求，包含包装容器，标签和特殊储存条件。

g) 所有特殊预防措施。

Packaging Instructions包装指令

4.19 Approved Packaging Instructions for each product, pack size and type should exist.

These should include, or have a reference to, the following:

a) Name of the product; including the batch number of bulk and finished product

b) Description of its pharmaceutical form, and strength where applicable;

c) The pack size expressed in terms of the number, weight or volume of the product in

the final container;

d) A complete list of all the packaging materials required, including quantities, sizes and types, with the code or reference number relating to the specifications of each

packaging material;

e) Where appropriate, an example or reproduction of the relevant printed packaging materials, and specimens indicating where to apply batch number references, and shelf life of the product;

f) Checks that the equipment and work station are clear of previous products, documents or materials not required for the planned packaging operations (line clearance), and that equipment is clean and suitable for use.

g) Special precautions to be observed, including a careful examination of the area and equipment in order to ascertain the line clearance before operations begin;

h) A description of the packaging operation, including any significant subsidiary operations, and equipment to be used;

i) Details of in-process controls with instructions for sampling and acceptance limits.

每种产品，包装规格和类型都应该有已批准的包装指令。

其中包含，或者是参考以下：

a)产品的名称，包含半成品和成品的批号

b)剂型和规格的描述如适用的话

Batch Processing Record批加工记录

4.20 A Batch Processing Record should be kept for each batch processed. It should be based on the relevant parts of the currently approved Manufacturing Formula and Processing Instructions, and should contain the following information:

a) The name and batch number of the product;

b) Dates and times of commencement, of significant intermediate stages and of completion of production;

c) Identification (initials) of the operator(s) who performed each significant step of the

process and, where appropriate, the name of any person who checked these

operations;

d) The batch number and/or analytical control number as well as the quantities of each

starting material actually weighed (including the batch number and amount of any

recovered or reprocessed material added);