Table of Contents

目录

 

CHAPTER 1 PHARMACEUTICAL QUALITY SYSTEM

 

第1章 药品质量体系

 

CHAPTER 2 PERSONNEL

 

第2章 人员

 

CHAPTER 3 PREMISES AND EQUIPMENT

 

第3章 厂房设施和设备

 

CHAPTER 4 DOCUMENTATION

 

第4章 文件

 

CHAPTER 5 PRODUCTION

 

第5章 生产

 

CHAPTER 6 QUALITY CONTROL

 

第六章 质量控制

 

CHAPTER 7 OUTSOURCED ACTIVITIES

 

第七章 外包活动

 

CHAPTER 8 COMPLAINTS AND PRODUCT RECALL

 

第八章 投诉和产品召回

 

CHAPTER 9 SELF INSPECTION

 

第9章 自检

 

CHAPTER 1 PHARMACEUTICAL QUALITY SYSTEM

第1章 药品质量体系

 

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 or Clinical Trial Authorisation, as appropriate, 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 its distributors. To achieve this quality objective reliably there must be a comprehensively designed and correctly implemented Pharmaceutical Quality System incorporating Good Manufacturing Practice and Quality Risk Management. It should be fully documented and its effectiveness monitored. All parts of the Pharmaceutical Quality 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 Authorised Person(s).

 

药品生产许可持有人（MAH）必须确保生产的药品符合其预期用途，符合注册要求或临床试验要求，且不会因安全性、质量或有效性不足而使患者处于风险之中。上述质量目标的实现是企业高级管理人员的责任，同时需要公司内部、供应商和分销商各部门和各级员工的参与和承诺。为了可靠地实现上述质量目标，必须有一个全面设计的，并正确实施药品生产质量管理规范（GMP）和质量风险管理的药品质量体系。药品质量体系应该完全文件化，并监测其有效性。药品质量体系的所有部分都应配备足够的合格人员，以及适当和充足的厂房、设备和设施。药品生产许可持有人（MAH）和受权人员（AP）需承担这些额外的法律责任。

 

The basic concepts of Quality Management, Good Manufacturing Practice (GMP) 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.

 

质量管理、良好制造规范(GMP)和质量风险管理三者是相互关联的。描述它们是为了强调它们的关系，以及它们对药品生产和控制的重要性。

 

PHARMACEUTICAL QUALITY SYSTEM 1 药品质量体系

 

（1 National requirements require manufacturers to establish and implement an effective pharmaceutical quality assurance system. The term Pharmaceutical Quality System is used in this chapter in the interests of consistency with ICH Q10 terminology. For the purposes of this chapter these terms can be considered interchangeable. 

 

1 国家要求制药企业建立和实施一个有效的药品质量保证体系。本章使用的药品质量体系相关术语与ICHQ10的术语是一致的，就本章而言，这些术语可以被认为是可互换的。

 

1.1 Quality Management 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 Management therefore incorporates Good Manufacturing Practice.

 

1.1质量管理是一个宽泛的概念，它涵盖单独或共同影响产品质量的所有问题。质量管理是确保药品质量达到其预期用途所作的有组织安排的总和。因此，质量管理包含药品生产质量管理规范（GMP）。

 

1.2 GMP applies to the lifecycle stages from the manufacture of investigational medicinal products, technology transfer, commercial manufacturing through to product discontinuation. However the Pharmaceutical Quality System can extend to the pharmaceutical development lifecycle stage as described in ICH Q10, which while optional, should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities.

 

1.2 GMP适用于从临床药品生产、技术转移、商业生产到产品退市的全生命周期阶段，而药品质量体系可以拓展到ICHQ10所述的药物开发生命周期阶段，这一拓展是非强制的，但应有助于创新和持续改进，并能加强药品开发和生产活动之间的联系。

 

1.3 The size and complexity of the company’s activities should be taken into consideration when developing a new Pharmaceutical Quality System or modifying an existing one. The design of the system should incorporate appropriate risk management principles including the use of appropriate tools. While some aspects of the system can be company-wide and others site-specific, the effectiveness of the system is normally demonstrated at the site level.

 

1.3在建立新的药品质量体系或调整现有的药品质量体系时，应考虑到公司活动的规模和复杂性。质量体系的设计应运用适当的风险管理原则，包括使用适当的工具。虽然质量体系的某些方面适用于全公司，也有些方面适用于特定厂房，但质量体系的有效性通常需在厂房层面证实。

 

1.4 A Pharmaceutical Quality System appropriate for the manufacture of medicinal products should ensure that:

 

1.4适用于药品生产的药品质量体系应确保：

 

(i) Product  is achieved by designing, planning, implementing, maintaining and continuously improving a system that allows the consistent delivery of products with appropriate quality attributes;

 

(i) 设计、规划、实施、维护和持续改进药品质量体系，以持续交付具有适当质量属性的产品；

 

(ii) Product and process knowledge is managed throughout all lifecycle stages;

 

(ii)产品和工艺知识的管理应贯穿所有生命周期阶段；

 

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

 

(iii)药品的设计和开发应考虑药品生产质量管理规范（GMP）的要求

 

(iv) Production and control operations are clearly specified and Good Manufacturing Practice adopted;

 

(iv) 生产和控制操作应有明确规定并符合良好生产规范；

 

(v) Managerial responsibilities are clearly specified;

 

(v) 应明确规定管理责任；

 

(vi) Arrangements are made for the manufacture, supply and use of the correct starting and packaging materials, the selection and monitoring of suppliers and for verifying that each delivery is from the approved supply chain;

 

(vi)应采取措施确保制造、供应和使用正确的原材料和包装材料，筛选和监控供应商，以及确认每次交付是来自经批准的供应链；

 

(vii) Processes are in place to assure the management of outsourced activities;

 

(vii)明确外包活动的管理；

 

(viii) A state of control is established and maintained by developing and using effective monitoring and control systems for process performance and product quality;

 

(viii)通过开发和使用有效的监控和生产、产品质量系统，来建立和维护控制状态；

 

(ix) The results of product and processes monitoring are taken into account in batch release, in the investigation of deviations, and, with a view to taking preventive action to avoid potential deviations occurring in the future;

 

(ix)在产品批放行、调查偏差时考虑到产品和过程监测结果，并采取预防措施，避免未来可能发生的潜在偏差；

 

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

 

(x)对中间产品进行所有必要的控制以及任何其他过程控制和验证；

 

(xi) Continual improvement is facilitated through the implementation of quality improvements appropriate to the current level of process and product knowledge;

 

(xi) 通过实施符合当前工艺和产品知识水平的质量改进，促进持续改进；

 

(xii) Arrangements are in place for the prospective evaluation of planned changes and their approval prior to implementation taking into account regulatory notification and approval where required;

 

(xii)在实施计划变更的预期评估及其批准前，考虑是否需要告知监管当局和得到监管当局的批准；

 

(xiii) After implementation of any change, an evaluation is undertaken to confirm the quality objectives were achieved and that there was no unintended deleterious impact on product quality;

 

(xiii)实施任何变更后，进行评估以确认质量目标已达到以及变更对产品质量没有潜在的影响；

 

(xiv) An appropriate level of root cause analysis should be applied during the investigation of deviations, suspected product defects and other problems. This can be determined using Quality Risk Management principles. In cases where the true root cause(s) of the issue cannot be determined, consideration should be given to identifying the most likely root cause(s) and to addressing those. Where human error is suspected or identified as the cause, this should be justified having taken care to ensure that process, procedural or system based errors or problems have not been overlooked, if present. Appropriate corrective actions and/or preventive actions (CAPAs) should be identified and taken in response to investigations. The effectiveness of such actions should be monitored and assessed, in line with Quality Risk Management principles;

 

(1iv)在调查偏差、可疑产品缺陷等问题时，应采用适当水平的根本原因分析。这可以通过质量风险管理原则来确定。在无法确定问题的真正根本原因的情况下，应考虑确定最可能的根本原因并解决这些原因。如果怀疑或确定为人为错误，则应谨慎处理，应确保不会忽视过程、程序或系统的错误或问题。调查后应确定并采取适当的纠正措施和/或预防措施(CAPAs)。根据质量风险管理原则，监测和评估这些措施的有效性；

 

(xv) 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;

 

(xv)在授权人员证明每批生产已按照药品生产、控制和放行相关的要求生产和控制之前，不得销售或供应药品；

 

(xvi) 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;

 

(xvi) 应采取适当的措施，尽可能保证药品在有效期内储存、分发和后续处理过程中的质量；

 

(xvii) There is a process for self-inspection and/or quality audit, which regularly appraises the effectiveness and applicability of the Pharmaceutical Quality System.

 

(xvii)应有自检和/或质量审计的程序，定期评估药品质量体系的有效性和适用性。

 

1.5 Senior management has the ultimate responsibility to ensure an effective Pharmaceutical Quality System is in place, adequately resourced and that roles, responsibilities, and authorities are defined, communicated and implemented throughout the organisation. Senior management’s leadership and active participation in the Pharmaceutical Quality System is essential. This leadership should ensure the support and commitment of staff at all levels and sites within the organisation to the Pharmaceutical Quality System.

 

1.5高级管理人员有责任确保药品质量体系的有效实施，确保体系配备充足的资源，并定义、沟通和实施整个组织中的角色、职责和权力分配。高级管理人员必须领导并积极参与到药品质量体系中。其领导方式应确保组织内各级和现场的工作人员对药品质量体系的支持和承诺。

 

1.6 There should be periodic management review, with the involvement of senior management, of the operation of the Pharmaceutical Quality System to identify opportunities for continual improvement of products, processes and the system itself.

 

1.6应在高级管理人员的参与下，对药品质量体系的运行进行定期的管理评审，以确定产品、过程和体系本身的持续改进。

 

1.7 The Pharmaceutical Quality System should be defined and documented. A Quality Manual or equivalent documentation should be established and should contain a description of the quality management system including management responsibilities.

 

1.7应对药品质量体系进行定义并文件化。建立质量手册或同等文件，并应包含对质量管理体系的描述，包括管理职责。