解除限制20100731 欧盟API GMP 中英文对照 CX 20110112

GM P

、质量控制和质量风险管理的质量体系。

2.2 Quality Risk Management

2.2

质量风险管理

2.20 Quality risk management is a systematic process for the assessment, control,

communication and review of risks to the quality of the active substance. It can be

applied both proactively and retrospectively.

2.20

质量风险管理 是一个对原料药质量风险进行评估、控制、交流和回顾的

系统的过程。它适用于前瞻和回顾。

2.21 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 through communication with the user of the active substance

- 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.

2.21

质量风险管理系统应该包含：

-

对质量风险的评价应该基于科学知识，并最终与保护患者相结合。

-

质量风险管理程序的执行力度、正式程度和文件化水平应当与 质量风险的

水平相匹配。

质量风险管理的开展和应用的例子可以在附件

20

中找到。

2.3 Responsibilities of the Quality Unit(s)

2.3

质量部门的职责

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

2.30

质量部门应该参与所有与质量相关的事务。

2.31 The quality unit(s) should review and approve all appropriate quality-related

documents.

2.31

所有与质量相关的文件都应该由质量部门来审核和批准。

2.32 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:

2.32

独立的质量部门的主要职责不应当委托。

这些职责包含但不限于：

1. Releasing or rejecting all APIs. Releasing or rejecting intermediates for

use outside the control of the manufacturing company;

1.

所有原 料药的放行和拒绝放行。用于生产企业控制范围以外的中间产品的

放行和拒绝放行。

2. Establishing a system to release or reject raw materials, intermediates,

packaging and labelling materials;

2.

制定一个 原料、中间产品、包装和标签材料的放行或拒绝放行的系统。

3. Reviewing completed batch production and laboratory control records of

critical process steps before release of the API for distribution;

3.

< br>在原料药销售放行前审核关键加工步骤的生产和实验室控制记录。

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

4.

确保关键偏差得到调查和解决。

5. Approving all specifications and master production instructions;

5

、批准所有的规格和生产指令。

6. Approving all procedures impacting the quality of intermediates or APIs;

6 .

批准所有影响中间产品和原料药质量的程序。

7. Making sure that internal audits (self-inspections) are performed;

7.

确保内部审计

(

自检

)

得到执行。

8. Approving intermediate and API contract manufacturers;

8.

批准中间产品和原料药的 合同生产商。

9. Approving changes that potentially impact intermediate or API quality;

9.

批准对中间产品和原料药有潜在质量影 响的变更。

10. Reviewing and approving validation protocols and reports;

10.

审核和批准验证方案和报告。

11. Making sure that quality related complaints are investigated and resolved;

< br>11.

确保质量相关的投诉得到了调查和解决。

12. Making sure that effective systems are used for maintaining and

calibrating critical equipment;

12.

确保有效的体系来对关键设备进行维护和校验。

13. Making sure that materials are appropriately tested and the results are

reported;

13.

确保物料 经过合适的检测并有结果报告。

14. Making sure that there is stability data to support retest or expiry dates

and storage conditions on APIs and/or intermediates where appropriate; and

14.

确保有稳定性数据 来支持原料药和

/

或中间产品的复检期或失效期和贮

存条件。

15. Performing product quality reviews (as defined in Section 2.5)

15.

执行产品质量回顾。

2.4 Responsibility for Production Activities

2.4

生产活动的职责

The responsibility for production activities should be described in writing, and should

include but not necessarily be limited to:

2.4

生产活动责任应当以书面形式加以描述

,

并且应当至少包括

,

但不局限于

:

1. Preparing, reviewing, approving and distributing the instructions for the

production of intermediates or APIs according to written procedures;

1.

根据书面程序起草、审核、批准 和分发中间产品或原料药的生产指令。

2. Producing APIs and, when appropriate, intermediates according to preapproved

instructions;

2.

根 据批准的指令生产原料药和中间产品（如果必要）。

3. Reviewing all production batch records and ensuring that these are

completed and signed;

3.

审核所有的批生产记录，确保操作完成并 有签名。

4. Making sure that all production deviations are reported and evaluated and

that critical deviations are investigated and the conclusions are recorded;

4.

确保所有的偏差都报告并评估过，关键偏差的调查和结论有记录。

5. Making sure that production facilities are clean and when appropriate

disinfected;

5.< /p>

确保生产设施清洁，在适当的时候经过消毒。

6. Making sure that the necessary calibrations are performed and records

kept;

6.

确保必要的校验得到 执行，并保存有记录。

7. Making sure that the premises and equipment are maintained and records

kept;

7.

确 保厂房和设备得到维护并保存有记录。

8. Making sure that validation protocols and reports are reviewed and

approved;

8.

确保验证方案和报告得到审核和批准。

9. Evaluating proposed changes in product, process or equipment; and

9.

评估产品、工艺或设备中 的变更建议。

10. Making sure that new and, when appropriate, modified facilities and

equipment are qualified.

10.

确保新的或改进后的设施和设备经过确认。

2.5 Internal Audits (Self Inspection)

2.5

内部审计（自检）

2.50 In order to verify compliance with the principles of GMP for APIs, regular

internal audits should be performed in accordance with an approved schedule.

2 .50

为证实与原料药《药品生产质量管理规范》原则相一致性

,

应当按照已经核

准日程进行定期的内部审计。

2.51 Audit findings and corrective actions should be documented and brought to the

attention of responsible management of the firm. Agreed corrective actions should be

completed in a timely and effective manner.

2.51

审计结果和整改措施应记录

,

并提请公司负责管理人员注意。已经同

意的纠正措施应当以有效的方式及时完成。

2.6 Product Quality Review

2.6

产品质量回顾

2.60 Regular quality reviews of APIs should be conducted with the objective of

verifying the consistency of the process. Such reviews should normally be conducted

and documented annually and should include at least:

2.60

定期的原料 药质量回顾应当以核实工艺的一致性为目的而进行。这样的回

顾应当每年进行一次并记录

,

至少包含：

- A review of critical in-process control and critical API test results;

-

关键过程控制和关键项目检测结果的回顾。

- A review of all batches that failed to meet established specification(s);

-

所有不合格批次的回顾。

- A review of all critical deviations or non-conformances and related

investigations;

-

所有关键偏差和不符合项及相关调查的回顾。

- A review of any changes carried out to the processes or analytical methods;

-

已经开展 的任何关于工艺和分析方法的变更的回顾。

- A review of results of the stability monitoring program;

-

稳定性监测结果的回顾。

- A review of all quality-related returns, complaints and recalls; and

-< /p>

所有质量相关的退货、投诉和召回的回顾。

- A review of adequacy of corrective actions.

-

纠正措施适当性的回顾。

2.61 The results of this review should be evaluated and an assessment made of

whether corrective action or any revalidation should be undertaken. Reasons for such

corrective action should be documented. Agreed corrective actions should be

completed in a timely and effective manner.

2.61

应当对质量回顾结果加以评估

,

并做出是否需要纠正措施和再验证的评估结

论。实施纠正措施的原因应当记录。核准的纠正措施应当有效并按期完成。

3 Personnel

3

人员

3.1 Personnel Qualifications

3.1

人员资质

3.10 There should be an adequate number of personnel qualified by appropriate

education, training and/or experience to perform and supervise the manufacture of

intermediates and APIs.

3.10

应当有足够数量具有合适教育

,

培训和

/

或经历资质的员工从事和监督中间

体 或原料药生产

。

3.11 The responsibilities of all personnel engaged in the manufacture of intermediates

and APIs should be specified in writing.

3.11

从事中间产品和原料药生产的人员则职责应当书面具体指定。

3.12 Training should be regularly conducted by qualified individuals and should

cover,at a minimum, the particular operations that the employee performs and GMP

as it relates to the employee's functions. Records of training should be maintained.

Training should be periodically assessed.

3.12

应 当定期举办由有资质人员进行的培训

,

其内容至少应当包括员工 所从事特

殊操作和与其职责有关的《药品生产质量管理规范》 。应当保存培训记录

,

并应对培训进行定期的评估。

3.2 Personnel Hygiene

3.2

人员卫生

3.20 Personnel should practice good sanitation and health habits.

3.20

人员应该养成良好的 健康和卫生习惯。

3.21 Personnel should wear clean clothing suitable for the manufacturing activity with

which they are involved and this clothing should be changed when appropriate.

Additional protective apparel, such as head, face, hand, and arm coverings, should be

worn when necessary, to protect intermediates and APIs from contamination.

3.21

人员应该穿着与他 们参与的生产活动所相适应的洁净服，并在适当的时候

进行更换。其它的防护服饰，比如 头、脸、手臂的遮挡物如果需要应该穿戴，以

避免中间产品和原料药被污染。

3.22 Personnel should avoid direct contact with intermediates or APIs.

3.22

人员应该避免直接接触中间产品和原料药。

3.23 Smoking, eating, drinking, chewing and the storage of food should be restricted

to certain designated areas separate from the manufacturing areas.

3.23

吸烟、吃、喝、咀嚼和食品的存贮应该限制在与生产区域隔离的指定区域。

3.24 Personnel suffering from an infectious disease or having open lesions on the

exposed surface of the body should not engage in activities that could result in

compromising the quality of APIs. Any person shown at any time (either by medical

examination or supervisory observation) to have an apparent illness or open lesions

should be excluded from activities where the health condition could adversely affect

the quality of the APIs until the condition is corrected or qualified medical personnel

determine that the person's inclusion would not jeopardize the safety or quality of the

APIs.

3.24

患传染性疾病或暴露在身体表面有开放性创伤的员工不应当从事有碍于原

料药质量的活动。任何人

,

在任何时候出现明显的疾病或开放 性损伤症状

(

不论

< br>是医学检查或监督观察

)

应当离开那些其健康状况可能影 响原料药质量的生

产场所

,

直到其健康情况改善或由有资质的医生检验结果表明该员工的工作

不会危害安全或原料药质量为止。

3.3 Consultants

3.3

顾问

3.30 Consultants advising on the manufacture and control of intermediates or APIs

should have sufficient education, training, and experience, or any combination thereof,

to advise on the subject for which they are retained.

3.30

从事中间体或原料药生 产以及控制的顾问应当具有足够的教育

,

培训和经验

或这些方面的综合

,

这 取决于从业者接受培训的情况。

3.31 Records should be maintained stating the name, address, qualifications, and type

of service provided by these consultants.

3.31

顾问的名称

,

地址

,

资质以及顾问可以提 供服务的种类的应当有书面记录。

4 Buildings and Facilities

4

厂房和设施

4.1 Design and Construction

4.1

设计和建造

4.10 Buildings and facilities used in the manufacture of intermediates and APIs

should be located, designed, and constructed to facilitate cleaning, maintenance, and

operations as appropriate to the type and stage of manufacture. Facilities should also

be designed to minimize potential contamination. Where microbiological

specifications have been established for the intermediate or API, facilities should also

be designed to limit exposure to objectionable microbiological contaminants as

appropriate.

4.10

生产中间体和原料药的厂房与设施的选址

,

设计和建造应当便于清洁

,

维护

和操作

,

以适应其生产类型和阶段进行。设施的设计应 着眼于使潜在污染最

小。对于已经确立微生物学规格标准的中 间体或原料药

,

设计设施时如果可

能应着眼于限制暴露于有害的微生物污染。

4.11 Buildings and facilities should have adequate space for the orderly placement of

equipment and materials to prevent mix- ups and contamination.

4.11

厂房和设施应该有足够的空间来有秩序的放置设备和物料，以避免混淆和

污染。

4.12 Where the equipment itself (e.g., closed or contained systems) provides adequate

protection of the material, such equipment can be located outdoors.

4.12

如果设备自身能对物料提供足够的保护的

(

如

,

封闭或密闭系统

)

可以安装在

户外。

4.13 The flow of materials and personnel through the building or facilities should be

designed to prevent mix-ups or contamination.

4.13

通过厂房或 设施的物流和人流应当设计成可以防止发生混淆或污染。

4.14 There should be defined areas or other control systems for the following

activities:

4.13

以 下活动应当在指定区域或其它控制系统控制下进行

:

-Receipt, identification, sampling, and quarantine of incoming materials, pending

release or rejection;

-

-Quarantine before release or rejection of intermediates and APIs;

-

中间产品和原料药在放行和拒绝放行前的待检。

-Sampling of intermediates and APIs;

-

中间产品和原料药的取样。

-Holding rejected materials before further disposition (e.g., return, reprocessing or

destruction).

-

拒收 物料在进一步处理前的存放（比如退货、返工或销毁）

-Storage of released materials;

-

放行物料的贮存。

-Production operations;

-

生产操作。

-Packaging and labelling operations; and

-

包装和贴签操作以及

-Laboratory operations.

-

实验室操作。

4.15 Adequate, clean washing and toilet facilities should be provided for personnel.

These washing facilities should be equipped with hot and cold water as appropriate,

soap or detergent, air driers or single service towels. The washing and toilet facilities

should be separate from, but easily accessible to, manufacturing areas. Adequate

facilities for showering and/or changing clothes should be provided, when

appropriate.

4.15

应当为员工提供足够的清洁和盥洗设施。这些洗涤设施应当适当地配备冷

热水

,

肥皂或洗涤剂

,

干燥 器或一次性毛巾。盥洗

,

厕所设施设施应当与生产区隔

离

,

但应当容易进入 。如果可能应当提供足够淋浴和

/

或更衣设施。

4.16 Laboratory areas/operations should normally be separated from production areas.

Some laboratory areas, in particular those used for in-process controls, can be located

in production areas, provided the operations of the production process do not

adversely affect the accuracy of the laboratory measurements, and the laboratory and

its operations do not adversely affect the production process or intermediate or API.

4.16

实验区域

/

操作通常应当同生产区隔离。

某些实验室

,< /p>

特别是用于过程控制的

,

可以位于生产区

,

但生产工艺操作不会对实验室测量的准确性产生负面影响

,

并且实验室和其操作不能对生产工艺或中间体或原料药质量产生 负面影响。

4.2 Utilities

4.2

设施

4.20 All utilities that could impact on product quality (e.g. steam, gases, compressed

air, and heating, ventilation and air conditioning) should be qualified and

appropriately monitored and action should be taken when limits are exceeded.

Drawings for these utility systems should be available.

4.20

所有可能影响产品质量的设施

(

即

,

蒸汽

,

气体

,

压缩空气和加热

,

通 风及空

调

)

都应当是确认过的

,

并进行适当监测

,

当 超过限度时采取措施。应当有这些设

施系统的图。

4.21 Adequate ventilation, air filtration and exhaust systems should be provided,

where appropriate. These systems should be designed and constructed to minimise

risks of contamination and cross- contamination and should include equipment for

control of air pressure, microorganisms (if appropriate), dust, humidity, and

temperature, as appropriate to the stage of manufacture. Particular attention should be

given to areas where APIs are exposed to the environment.

4.21

如果需要

< br>,

应当提供足够的通风

,

空气过 滤和排气系统。这些系统应当设计

成并建造成使污染和交叉污染风险降低到最小

,

并且应当有控制空气压力

,

< br>微生

物

(

如果需要

),

灰尘

,

湿度和温度的设备

,

以便适应该生产阶段。特别需要 注意

的是那些原料药暴露到环境的区域。

4.22 If air is recirculated to production areas, appropriate measures should be taken to

control risks of contamination and cross-contamination.

4.22

如果回风需要循环到生产区域，应该有适当的措施控制污染和交叉污染。

4.23 Permanently installed pipework should be appropriately identified. This can be

accomplished by identifying individual lines, documentation, computer control

systems,or alternative means. Pipework should be located to avoid risks of

contamination of the intermediate or API.

4.23

永久安装的管道应该有适当的标示。这可 以由标识每根管线

,

记录

,