01 中国GMP对QA的要求

第八条质量保证是质量管理体系的一部分。企业必须建立质量保证系统，同时建立完整的文件体系，以保证系统有效运行。

第九条质量保证系统应当确保：

(一) 药品的设计与研发体现本规范的要求；

(二) 生产管理和质量控制活动符合本规范的要求；

(三)管理职责明确；

(四)采购和使用的原辅料和包装材料正确无误；

(五)中间产品得到有效控制；

(六)确认、验证的实施；

(七)严格按照规程进行生产、检查、检验和复核；

(八)每批产品经质量受权人批准后方可放行；

(九)在贮存、发运和随后的各种操作过程中有保证药品质量的适当措施；

(十)按照自检操作规程，定期检查评估质量保证系统的有效性和适用性。

第十条药品生产质量管理的基本要求：

(一)制定生产工艺，系统地回顾并证明其可持续稳定地生产出符合要求的产品；

(二)生产工艺及其重大变更均经过验证；

(三)配备所需的资源，至少包括：

1.具有适当的资质并经培训合格的人员；

2.足够的厂房和空间；

3.适用的设备和维修保障；

4.正确的原辅料、包装材料和标签；

5.经批准的工艺规程和操作规程；

6.适当的贮运条件。

(四)应当使用准确、易懂的语言制定操作规程；

(五)操作人员经过培训，能够按照操作规程正确操作；

(六)生产全过程应当有记录，偏差均经过调查并记录；

(七)批记录和发运记录应当能够追溯批产品的完整历史，并妥善保存、便于查阅；

(八)降低药品发运过程中的质量风险；

(九)建立药品召回系统，确保能够召回任何一批已发运销售的产品；

(十)调查导致药品投诉和质量缺陷的原因，并采取措施，防止类似质量缺陷再次发生。

02 ICH Q7中对质量管理的描述

QUALITY MANAGEMENT 质量管理

2.1 Principles 原则

2.10 Quality should be the responsibility of all persons involved in manufacturing.

质量应该是所有参与生产的人员的职责。

2.11 Each manufacturer should establish, document, and implement an effective system for managing quality that involves the active participation of management and appropriate manufacturing personnel.

2.12 The system for managing quality should encompass the organisational structure, procedures, processes and resources, as well as activities necessary to ensure confidence that the API will meet its intended specifications for quality and purity. All quality related activities should be defined and documented.

2.13 There should be a quality unit(s) that is independent of production and that fulfills both quality assurance (QA) and quality control (QC) responsibilities. This can be in the form of separate QA and QC units or a single individual or group, depending upon the size and structure of the orgnization.

2.14 The persons authorised to release intermediates and APIs should be specified.

2.15 All quality related activities should be recorded at the time they are performed.

2.16 Any deviation from established procedures should be documented and explained. Critical deviations should be investigated, and the investigation and its conclusions should be documented.

2.17 No materials should be released or used before the satisfactory completion of evaluation by the quality unit(s) unless there are appropriate systems in place to allow for such use (e.g. release under quarantine as described in Section 10.20 or the use of raw materials or intermediates pending completion of evaluation).

2.18 Procedures should exist for notifying responsible management in a timely manner of regulatory inspections, serious GMP deficiencies, product defects and related actions (e.g., quality related complaints, recalls, regulatory actions, etc.).

2.2 Responsibilities of the Quality Unit(s)

质量单元的职责

2.20 The quality unit(s) should be involved in all quality-related matters.

2.21 The quality unit(s) should review and approve all appropriate quality-related documents.

2.22 The main responsibilities of the independent quality unit(s) should not be delegated. These responsibilities should be described in writing and should include but not necessarily be limited to:

1. Releasing or rejecting all APIs. Releasing or rejecting intermediates for use
outside the control of the manufacturing company;

2. Establishing a system to release or reject raw materials, intermediates,
packaging and labelling materials;

3. Reviewing completed batch production and laboratory control records of critical process steps before release of the API for distribution;

4. Making sure that critical deviations are investigated and resolved;

14. Making sure that there is stability data to support retest or expiry dates and storage conditions on APIs and/or intermediates where appropriate;

15. Performing product quality reviews

(as defined in Section 2.5).

03 WHO GMP中的描述

Quality management in the drug industry

医药行业的质量管理

In the drug industry at large, quality management is usually defined as the aspect of management function that determines and implements the “quality policy”,i.e. the overall intention and direction of an organization regarding quality, as formally expressed and authorized by top management. The basic elements of quality management are:

在大的医药行业中，质量管理常常被定义为管理职能中规定并执行“质量政策”的那方面职能。比如组织质量相关的总体意图和方向，由最高管理层正式表达和授权。

质量管理的基本要素有：

— an appropriate infrastructure or “quality system”, encompassing the organizational structure, procedures, processes and resources;

— systematic actions necessary to ensure adequate confidence that a product (or service) will satisfy given requirements for quality. The totality of these actions is termed “quality assurance”.

Within an organization, quality assurance serves as a management tool. In contractual situations, quality assurance also serves to generate confidence in the supplier. The concepts of quality assurance, GMP and quality control are interrelated aspects of quality management. They are described here in order to emphasize their relationship and their fundamental importance to the production and control of pharmaceutical products.

1. Quality assurance 质量保证

1.1 Principle. 原则

“Quality assurance” is a wide-ranging concept covering all matters that individually or collectively influence the quality of a product. It is the totality of the arrangements made with the object of ensuring that pharmaceutical products are of the quality required for their intended use. Quality assurance therefore incorporates GMP and other factors, including those outside the scope of this guide such as product design and development.

1.2 The system of quality assurance appropriate to the manufacture of pharmaceutical products should ensure that:

(a) pharmaceutical products are designed and developed in a way that takes account of the requirements of GMP and other associated codes such as those of good laboratory practice (GLP) 1 and good clinical practice (GCP);

(b) production and control operations are clearly specified in a written form and GMP requirements are adopted;

(c) managerial responsibilities are clearly specified in job descriptions;

(d) arrangements are made for the manufacture, supply and use of the correct starting and packaging materials;

(e) all necessary controls on starting materials, intermediate products, and bulk products and other in-process controls, calibrations, and validations are carried out;

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

(g) pharmaceutical products are not sold or supplied before the authorized persons (see also sections 9.11 and 9.12) have certified that each production batch has been produced and controlled in accordance with the requirements of the marketing authorization and any other regulations relevant to the production, control and release of pharmaceutical products;

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

(i) there is a procedure for self-inspection and/or quality audit that regularly appraises the effectiveness and applicability of the quality assurance system;

(j) deviations are reported, investigated and recorded;

(k) there is a system for approving changes that may have an impact on product quality;

(l) regular evaluations of the quality of pharmaceutical products should be conducted with the objective of verifying the consistency of the process and ensuring its continuous improvement.

1.3 The manufacturer must assume responsibility for the quality of the pharmaceutical products to ensure that they are fit for their intended use, comply with the requirements of the marketing authorization 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 of staff in many different departments and at all levels within the company, the company’s suppliers, and the distributors. To achieve the quality objective reliably there must be a comprehensively designed and correctly implemented system of quality assurance incorporating GMP and quality control. It should be fully documented and its effectiveness monitored. All parts of the quality assurance system should be adequately staffed with competent personnel, and should have suitable and sufficient premises, equipment, and facilities.

2. Good manufacturing practices for pharmaceutical products (GMP)

2.1 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 authorization. GMP are aimed primarily at diminishing the risks inherent in any pharmaceutical production. Such risks are essentially of two types: cross contamination (in particular of unexpected contaminants) and mix-ups (confusion) caused by, for example, false labels being put on containers. Under GMP:

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

(b) qualification and validation are performed;

(c) all necessary resources are provided, including:

合适的有资质并经过培训的人员；
(ii) adequate premises and space;

足够的厂房和空间；
(iii) suitable equipment and services;

合适的设备和服务；
(iv) appropriate materials, containers and labels;

批准的程序和工艺规程；
(vi) suitable storage and transport;

合适的储存和运输；
(vii) adequate personnel, laboratories and equipment for in-process
controls;

在生产中做记录（手工和/或通过记录仪）以显示所有由规定的程序和规程要求的所有步骤都已经在事实上被执行，产品的数量和质量跟期望的一样；任何重大偏差都被完整记录并调查；

(j) complaints about marketed products areexamined, the causes of quality defects investigated, and appropriate measures taken in respect of the defective products to prevent recurrence.