研发，如何做质量管理？|WHO最新发布指南

11月11日，世界卫生组织（WHO）发布了“研究和开发设施的良好实践” 指南（Good practices for research and development facilities）的征求意见稿。WHO指出，就开发批、中试批生产以及相应的稳定性数据，目前没有相关的法规指南对稳定性、工艺验证和分析方法的开发和验证提出具体要求，因此开发本文件非常有必要。本文件为研发机构提供了有关GMP方面的指南，目的是确保遵循正确的系统，保证产品、工艺、程序和数据的适当性、可靠性和质量。

本指南主体部分分为22个章节，内容如下：

1.背景
2.简介
3.范围
4.质量管理
5.质量风险管理
6.卫生
7.确认与验证
8.外包活动
9.自检和质量审计
10.人员
11.培训
12.设施
13.设备和仪器
14.物料
15.文档
16.加工和工艺验证
17.质量控制
18.稳定性研究
19.分析程序的制定
20.技术转移
21.生命周期方法
22.清洁程序的开发和清洁验证


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1-3章：研发设施，要不要GMP？|WHO最新发布指南

以下是该指南的4-7章的内容：
4. 质量管理
Quality management 

4.1. There should be a quality management system encompassing adequate resources, a written organizational structure and procedures to follow.

应该有一个质量管理体系，包括充分的资源、书面话的组织结构和可以遵循的程序。

4.2. The necessary resources should include, for example:

a) a sufficient number of appropriately qualified, trained personnel;

b) adequate premises and space;

c) suitable equipment and services;

d) appropriate materials, containers and labels；and

e) suitable storage and transport.

必要的资源应包括，例如：

a）足够数量的经过适当培训的有资质人员；

b）充分的场所和空间；

c）合适的设备和服务；

d）适当的材料、容器和标签；

e）适当的储存和运输。

4.3. Roles, responsibilities and authorities should be defined, communicated and implemented.

角色、职责和权限应定义、沟通和实施。

4.4. The quality system should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities.

质量体系应促进创新和持续改进，并加强药物开发与生产活动之间的联系。

4.5 All parts of the quality system should be adequately resourced and maintained, including with sufficient competent personnel, suitable premises, equipment and facilities.

质量体系的所有部分应有充分的资源和维护，包括有充分的有资质人员，合适的场所、设备和设施。

4.6 Initial research, as well as development activities, should be defined and documented. The detail should be in accordance with risk assessment and the increasing scale of GMP requirements from early to final stages of development.

应该定义和记录初步研究以及开发活动。其详细程度，应与风险评估、以及从开发的早期到最终阶段不断增加的GMP要求相一致。

4.7 The quality system should ensure, as applicable and according to the stage of research and development, that:

质量体系应根据研究和开发阶段的要求，确保：

managerial responsibilities are clearly specified in job descriptions;

在岗位说明书中明确规定管理职责；

instructions and procedures are written in clear and unambiguous language;

指导和程序以清晰明确的语言编写；

procedures are correctly carried out;

正确执行程序；

records are made (manually and/or by recording instruments) during production and quality control;

在生产和质量控制期间（手动和/或通过记录仪器）进行记录；

any significant deviations are recorded, investigated and the appropriate action taken;

记录、调查任何重大偏差，并采取适当措施；

records are maintained;

保持记录；

there is a system for quality risk management (QRM);

有质量风险管理（QRM）系统；

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

对于生产、供应和使用正确的起始和包装材料，进行相应的安排；

all necessary controls on starting materials, intermediate products, bulk products and other in-process controls are carried out;

对原材料、中间体、半成品和其它中制措施，进行所有必要的控制；

calibrations and validations are carried out where appropriate;

适当时，进行校准和验证；

the product and process knowledge is managed;

产品和工艺知识得到管理；

products are designed and developed in accordance with applicable good practices (GxP);

根据适用的良好实践（GxP）设计和开发产品；

production and control operations are clearly specified in written form;

以书面形式，明确规定生产和控制操作；

continual improvement is facilitated through the implementation of quality improvements appropriate to the current level of process and product knowledge;

通过实施适合于当前工艺和产品知识水平的质量改进，来促进持续改进；

product realization is achieved;

完成产品的可实现化；

cleaning procedures are developed and validated;

制定并验证清洁程序；

stability testing is done following written procedures and protocols；and

按照书面程序和草案进行稳定性测试；

data meet ALCOA+ requirements.

数据符合ALCOA +要求。

4.8 There should be periodic management review with the involvement of senior management.

应在高级管理层的参与下，进行定期的管理层审查。

5.质量风险管理
 Quality risk management 

5.1. A system of quality risk management (QRM) should be implemented. The system should ensure that risks are identified based on scientific knowledge and experience. The appropriate controls should be identified and implemented to mitigate risks.

应实施质量风险管理（QRM）系统。该系统应确保根据科学知识和经验确定风险。应确定并实施适当的控制措施，以减轻风险。

5.2. The level of effort, formality and documentation of the QRM process is commensurate with the level of risk and the stage from research to development, to commercial batch manufacturing and control (see Figure 1).

QRM流程的工作量、形式和文件记录的水平，应与风险水平以及从研究、到开发再到商业批生产和控制的阶段相对应（见图1）。

5.3. Systems should be in place to manage and minimize the risks inherent in research and development in order to ensure the ultimate quality, safety and efficacy of products；and the reliability of data.

应建立系统来管理和减少研发中固有的风险，以确保产品的最终质量，安全性和有效性；以及数据的可靠性。

5.4. Risk assessments should be periodically reviewed in light of improvements, current technology, scientific knowledge and experience.

应根据改进情况、当前技术、科学知识和经验，定期审查风险评估。

6. 清洁与卫生
Sanitation and hygiene 

6.1. Procedures should be implemented to maintain sanitation and hygiene. The scope of sanitation and hygiene covers personnel, premises, equipment and apparatus, production materials and containers, and products for cleaning and disinfection.

应执行程序，以保持清洁与卫生。清洁和卫生范围包括人员、场所、设备和器具、生产材料、容器，以及清洁和消毒产品。

6.2. Potential sources of contamination should be eliminated.

应消除潜在的污染源。

7.  确认与验证
Qualification and validation

7.1. Qualification and validation required should be identified based on risk assessment and, in addition, should be appropriate to the stage of research and development.

应基于风险评估来确定所需的确认与验证，此外，还应适合于研发阶段。

7.2. The qualification and validation policy and approach should be defined and documented, for example, in a validation master plan.

例如，应在验证主计划中，定义和记录确认与验证的策略及方法。

7.3. Where qualification and validation is carried out, the responsibility of performing validation should be clearly defined.

在进行确认与验证时，应明确规定执行验证的责任。

7.4. Qualification and validation should provide documentary evidence that specifications and other requirements are met. Protocols and reports should be made available, when required.

确认与验证应提供证明，即满足质量标准和其它要求的书面证据。必要时，应提供草案和报告。

7.5. Where process validation, cleaning validation and analytical procedure validation is done as a part of development, procedures and protocols should be followed. Reports should be available and retained.

在开发过程中，进行工艺验证、清洁验证和分析方法验证时，应遵循程序和草案。报告应可查，并进行保留。

       文章来源：PharmLink

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