药用产品GMP指南第一部分翻译.docx

PHARMACEUTICAL INSPECTION CONVENTION
PHARMACEUTICAL INSPECTION CO-OPERATION SCHEME
药品检验公约
药品检验合作计划
GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS PART I
药用产品良好生产规范指南第一部分

目录

第一章 质量管理 2
第二章人员 11
第三章 厂房设施 17
第四章 文件 25
第五章 生产 41
第六章质量控制 53
第七章 委托生产与委托检验 62
第八章 产品投诉和召回 66
第九章 自检 69

CHAPTER 1
第一章 质量管理
QUALITY MANAGEMENT
PRINCIPLE 原则
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, and thus Quality Control and Quality Risk Management. It should be fully documented and its effectiveness monitored. All parts of the Quality Assurance systems 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 authorised person(s).
生产许可证持有人必须生产药品，从而确保药品适合预期用途、符合相应的上市许可证或临床试验许 可证要求，不因为安全性问题、质量问题或有效性问题而把患者置于风险之中。实现上述质量目标是公司高级管理人员的职责，并要求公司的供应商、销售商，公司内所有各级员工和许多不同部门的员工共同参和、一起努力。要可靠地实现这一质量目标，必须综 合设计一个整合药品生产质量管理规范（GMP）和质量控制、质量风险管理的制药质量保证体系并正确实施。质量体系应当全面文件化，并监察其有效性。整个制药质量体 系应当配备充足的具有资质的人员，以及充分并适用的建筑物、设备和设施。生产许可证持有人以及质量受权人有额外的法律责任。
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、质量控制以及质量风险管理的基本概念是相互关联的。在这里对其进行描述是为了强调它们之间的联系以及其对药品生产和控制的重要性。
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.
质量保证是一个宽泛的概念，涵盖所有因素，这些因素单独或共同影响产品质量。质量保证是为了保证药品质量符合预期用途，而进行的有组织的安排的总和。因此，质量保证中包含着药品生产质量管理规范以及本指南的范围内的其他因素。
The system of Quality Assurance appropriate for the manufacture of medicinal products should ensure that:
一个适当的质量保证体系应当确保：
i. medicinal products are designed and developed in a way that takes account of the requirements of Good Manufacturing Practice ;
药品的设计和开发应考虑药品生产质量管理规范的要求；
ii. production and control operations are clearly specified and Good Manufacturing Practice adopted;
对生产和控制操作进行明确规定，并符合药品生产质量管理规范的要求；
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;
对下述活动均有协议约束：生产、供应、使用正确的起始物料和包装材料。
v. all necessary controls on intermediate products, and any other inprocess controls and validations are carried out;
对中间产品以及其他任何中间过程控制和验证实施所有必要的控制；
vi. the finished product is correctly processed and checked, according to the defined procedures;
成品根据确定的程序进行正确生产和检测；
vii. medicinal products are not sold or supplied before an authorised 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;
质量受权人需签发证明以确认每一批次药品的生产和控制均符合上市许可要求以及和药品生产 、控制和放行相关的任何其他法规要求，未经质量受权人签发证明的药品不得销售或供货；
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;
药品贮存 、发运和后续处理确保有满意的管理规程，从而尽量保证药品货架期内的质量
ix. there is a procedure for self-inspection and/or quality audit, which regularly appraises the effectiveness and applicability of the quality assurance system.
有自检和 / 或质量审计规程，以定期评价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
1.2 Good Manufacturing Practice is that part of Quality Assurance which ensures that Medicinal 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. Good Manufacturing Practice is concerned with both production and quality control. The basic requirements of GMP are that:
药品生产质量管理规范是质量管理体系的一部分，保证按适合预期用途的质量标准及上市许可、临床试验许可或产品质量标准要求始终如一地生产及控制产品。药品生产质量管理规范涉及生产和质量控制。药品生产质量管理规范的基本要求是：
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;
所有生产工艺得到明确规定、按照经验经过系统的审核，并经过证明表明有能力始终如一地
生产具有所需质量且符合质量标准的药品
ii. critical steps of manufacturing processes and significant changes to the process are validated;
生产工艺的关键步骤以及重大的工艺变更已经验证；
iii. all necessary facilities for GMP are provided including:
提供了 GM P需要的所有设施，包 括 ：
a. appropriately qualified and trained personnel; 有适当资质并经过培训的员工；
b. adequate premises and space; 充足的厂房和空间 ；
c. suitable equipment and services; 适 当 的 设 备 及 保 养 ；
d. correct materials, containers and labels; 恰当的材料、容 器 和 标 签 ；
e. approved procedures and instructions; 经批准的规程和操作方法；
f. suitable storage and transport; 合 适 的 贮 存 和 运 输 ；
iv. instructions and procedures are written in an instructional form in clear and unambiguous language, specifically applicable to the facilities provided;
操作方法和规程应当使用有指导意义的方式来书写，并且条理清楚、用语明确 ，特别是要适用于相应的设施 ；
v. operators are trained to carry out procedures correctly;
操作人员接受过正确执行规程的培训；
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; 在生产过程中进行了记录，可由手工和/ 或仪器记录，以证明规程和操作要求的所有步骤切实得到了执行，以及产品的质量和数量达到预期要求；所有重大偏差得到了完整记录、经过了调查
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;
生产记录包括销售记录以易懂且可获得的方式得到了保留，使整个批次的完整历史可追溯；
viii. the distribution (wholesaling) of the products minimises any risk to their quality;
降低产品销售过程中的质量风险；
ix. a system is available to recall any batch of product, from sale or supply;
有药品召回系统，确保任何一批产品都能从销售商或供应处收回；
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 re-occurrence.
对产品投诉进行检查，调查质量缺陷原因，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. The basic requirements of Quality Control are that:
质量 控 制 是 G M P 的一部分，涉及取样、质量标准、检验，同样也涉及组织机构、文件和放行规程，以保证切实执行了必要的相关检验，并且确保物料或产品被判定符合要求之前不被放行使用或销售。质量控制的基本要求是：
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;
有 充足 的设施设 备、经过培训的人员及经过批准的规程用于起始物料、包 装 材 料 、中间体、半成品和成品取样和检验，以及 G M P 要 求 的 环 境 监 测
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;
由经过批准的人员按经过批准的方法对起始物料、包装材料、中间产品、半成品、成 品 取 样 ；
iii. test methods are validated; 检 验 方法 经过 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;
由手工和/ 或仪器做了记录，以证明所有要求的取样、检查和检验规程切实得到了执行。任何偏差得到了完整记录和调查；
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;
成品中的活性成分符合上市许可或临床试验许可的定性和定量要求，及符合纯度要求，并贮
存在适当的容器中、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;
物料 、中间体、半成品及成品的检查和检验结果有记录，成品按质量标准做了正式评估。产品评估包括回顾和评估相关生产文件，以及评估对特定规程的偏差；
vii. no batch of product is released for sale or supply prior to certification by an authorised person that it is in accordance with the requirements of the relevant authorisations;
在质量受权人确认产品批次符合相应许可要求之前，任何批次不被放行销售或供货；
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.
留有足够的起始物料和成品对照样品， 以备将来有需要的时候对产品进行检验，样品包装方式和对应的产品最终包装方式相同。
PRODUCT QUALITY REVIEW产品质量回顾
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:
应当对所有获得批准的药品，包括仅供出口的药品，进行定期的或滚动式的质量回顾，质量回顾的目的是确认现有工艺的一致性、起始物料和成品现行质量标准的适宜性，强调任何趋势并识别产品和工艺改进点。通常应当每年回顾并文件化，回顾中还应当考虑以前的回顾情况，并至少应当包括：
i. A review of starting materials including packaging materials used in the product, especially those from new sources.
回顾产品所用起始物料、包装材料，特别是来自新供应商的起始物料和包装材料，
ii. A review of critical in-process controls and finished product results.
回顾关键中间过程控制和成品结果。
iii. A review of all batches that failed to meet established specification(s) and their investigation.
回顾未能符合既定质量标准的所有批次及其调查结果。
iv. A review of all significant deviations or non-conformances, their related investigations, and the effectiveness of resultant corrective and preventative actions taken.
回顾所有重大偏差或不符合事件和相关调查，以及后续纠正和预防措施的有效性。
v. A review of all changes carried out to the processes or analytical methods.
回顾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.
回顾已递交的、 已批准的或被拒绝的上市许可变更，包括已递交的、 已批准的或被拒绝的第三 国 （ 仅供出口）上市许可变更资料。
vii. A review of the results of the stability monitoring programme and any adverse trends.
回顾稳定性监测程序的结果以及任何不良的趋势。
viii. A review of all quality-related returns, complaints and recalls and the investigations performed at the time.
回顾和质量相关的所有退货、投诉和召回，以及当时实施的调查。
ix. A review of adequacy of any other previous product process or equipment corrective actions.
回顾任何其他先前产品工艺或设备纠正措施的适宜性。
x. For new marketing authorisations and variations to marketing authorisations, a review of post-marketing commitments.
对于新的上市许可和上市许可变更，回顾上市后承诺。
xi. The qualification status of relevant equipment and utilities, e.g. HVAC, water, compressed gases, etc.
回顾相关设备和公用系统的确认状态，例如空气净化系统、制水系统、压缩空气系统等。
xii. A review of any contractual arrangements as defined in Chapter 7 to ensure that they are up to date.
回顾第7 章规定的所有合同、协 议 ，以确保未过时。
The manufacturer and marketing authorisation holder should evaluate the results of this review 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.
生产企业，或是上市许可证持有人，如果生产企业不是上市许可证持有人的话，应当在制药质量体系下评估产品质量回顾的结果，并评估是否应当釆取纠正和预防措施或是任何再验证。对于现有管理活动及这些管理活动的回顾，应当有管理规程，并通过自检确认这些规程的有效性。经过科学论证后 ，可以按产品类别进行质量回顾，例如固体剂型、液体剂型、无菌产品等。
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 authorized 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.
如果上市许可证持有人不是生产企业，各方之间应当签订技术协议，规定各自在产品貭量回顾中的责任。授权人和销售许可持有人负责最后一批认证，应确保及时准确的的进行质量回顾。
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.
质量风险管理是一个用于药品质量风险评估、控 制 、交流和评审的系统过程。可以采用前瞻性或回顾性形式。
1.6 The quality risk management system should ensure that: 质量风险 管理的原 则是 ：
- 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;
质量风险评估是以科学知识和对工艺的经验为基础，并最终和保护患者相关联。
- the level of effort, formality and documentation of the quality risk management process is commensurate with the level of risk.
质量风险管理过程的投入、正式程度和文件应当和风险水平相适应。
Examples of the processes and applications of quality risk management can be found inter alia in Annex 20.
在附录20 中所述的质量风险管理的过程和应用实例。

CHAPTER 2
第二章人员
PERSONNEL
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 u