WHO第961号技术报告_附件7_药物生产技术转移指南(中英文)

与各方和所有适用法规的要求。

1.3 Literature searches revealed little information on the subject originating from national or

regional regulatory bodies. Guidance on intracompany transfers was prepared by the International

Society for Pharmaceutical Engineering (ISPE) (

1

).

文献查阅显示来自于国家或 地区药监部门关于本主题的信息非常少。

ISPE

（

）有一份关于跨公司转

移指南。

1.4 The ever changing business strategies of pharmaceutical companies increasingly involve intra-

and intercompany transfers of technology for reasons such as the need for additional capacity,

relocation of operations or consolidations and mergers. The WHO Expert Committee on

Specifications for Pharmaceutical Preparations, therefore, recommended in its forty second report

that WHO address this issue through preparation of WHO guidelines on this matter (

2

).

制药企业的经营策略导致在 公司间、

公司内进行技术转移日益增加，

原因各种各样，

例如增加产能的

需求、寻求新的生产场所、合并和收购。因此，

WHO

制剂质量标准专家委员会在

WHO

第

42

期报

告中对 制剂的

WHO

指南中阐述了对此问题的推荐。

< br>

1.5 Transfer of technology requires a documented, planned approach using trained and

knowledgeable personnel working within a quality system, with documentation of data covering all

aspects of development, production and quality control. Usually there is a sending unit (SU), a

receiving unit and the unit managing the process, which may or may not be a separate entity. For

―contract manufacturing‖ please see good manufacturing practices (GMP) (

3

).

技术转移需要一种记录的计划方式，人员应经过培训、有知识背景，在一个质量体系下工作，数据记

录应覆盖研发、生产和质量控制各方面。一般会有一个转出方

(SU )

，一个接收方和管理工艺的单位。

管理工艺的单位可以是一个 独立的主体，也可不是。关于

―

合同制造

‖

，请参见

GMP

（

3

）。

1.6 For the transfer to be successful, the following general principles and requirements should be

met:

为使转移成功，应符合以下一般原则和要求

?

the project plan should encompass the quality aspects of the project and be based upon the

principles of quality risk management;

项目计划应基于质量风险管理，对项目的质量方面起到指导作用

?

the capabilities of the SU and at the RU should be similar, but not necessarily identical, and

facilities and equipment should operate according to similar operating principles;

接收单位和转出单位的产能应相似，但不是必须的，设施和设 备应根据相似的操作原则进行操作

?

a comprehensive technical gap analysis between the SU and RU including technical risk

assessment and potential regulatory gaps, should be performed as needed;

< /p>

如有需要，

应对转出单位和接收单位进行综合技术差异分析，

包括技术风险评估和潜在法规差异

?

adequately trained staff should be available or should be trained at the RU:

接收单位应具有经过充分培训地员工，或培训其员工

—

regulatory requirements in the countries of the SU and the RU, and in any countries

where the product is intended to be supplied, should be taken into account and interpreted

consistently throughout any transfer programme project; and

—

接收单位和转出单位的所在国法规要求，以及任何该产品将要销售的国家的法规要求，均

应进行考虑，并在整个转移程序项目期间有一致的解释

—

there should be effective process and product knowledge transfer.

—

工艺和产品知识转移应有效果

1.7 Technology transfer can be considered successful if there is documented evidence that the RU

can routinely reproduce the transferred product, process or method against a predefined set of

specifications as agreed with the SU. < /p>

如果有文件化的证据证明接收单位可以正常地再次生产出所转移的产品、

< br>工艺或方法，

使用其符合与

转出单位协商同意的一系列既 定的规格，则可以认为技术转移已经成功。

1.8 In the event that the RU identifies particular problems with the process during the transfer, the

RU should communicate them back to the SU to ensure continuing knowledge management.

如果接收单位在转移过程中发现工艺有一些特别的问题，

应反馈回转出单位，

以保证继续进行知识管

理。

1.9 Technology transfer projects, particularly those between different companies, have legal and

economic implications. If such issues, which may include intellectual property rights, royalties,

pricing, conflict of interest and confidentiality, are expected to impact on open communication of

technical matters in any way, they should be addressed before and during planning and execution

of the transfer.

技 术转移项目，是那些不同公司间转移的项目，牵涉到法律和经济方面。如果这些方面，可能会包括

知识产权、版税、价格、利益和保密的冲突，将会影响到技术问题的公开交流，那么在计划和实施技

术转移之前和过程中应进行说明。

1.10 Any lack of transparency may lead to ineffective transfer of technology.

缺乏透明度可能会导致技术转移没有效果

1.11 Some of the principles outlined in this document may also be applicable to manufacturing

investigational pharmaceutical products for clinical trials as part of research and development, but

this is not the main focus of this guidance and has been excluded due to the complexity of the

processes.

在本文件中列出的有些原则可能也适用于作为生产临床药品，

作为研发的一部分，

但这不是本指南主

要关注点，并由于其过程太复杂因此未包括在其中 。

1.12 Some of the responsibilities outlined in this document for the SU may also be considered to be

part of the management unit responsibilities.

在本文件件中列出的转出单位的一些职责可能也 可以考虑作为管理单位的职责。

2.

Scope

范围

Note

: This section specifically provides for transfer of quality control (QC) methods where a

technical agreement exists (SU manufacturer to RU manufacturer or SU manufacturer to RU QC

laboratory). Where no such technical agreements exist (e.g. testing by national laboratories or

testing for procurement agencies) a number of the points listed in section 2.4 may not

be workable,and alternative approaches may be required.

注：

本部分特别提供给有技术协议存在时，

质量控制方法的转移

（转出生产方给接收生产单位生产方

或转出单位生产方给接收单位

QC

化验室）。如果没有这样的技术协议存在（例如，由一个国家化验

室进行检查，或由采购代理进行检测），在

2.4

部分 列出的一些项可能用不上，那么可能需要替代的

方法。

2.1 This document gives guidance in principle and provides general recommendations on the

activities necessary to conduct a successful intraorintersite transfer of technology as described in

the Introduction to these guidelines. The intention is to address the basic considerations needed for

a successful transfer in order to satisfy the regulatory authority defined for the transfer process.

本文件给出了原则性指南，

如本指南介绍中所述，

提 供了在工厂内、

不同工厂间成功进行支持转移所

需的活动建议，

意在说明进行成功的技术转移所需的基本考虑，

以满足在工艺转 移中涉及的法规当局

的要求。

2.2 The guidelines will be applied to manufacturing active pharmaceutical ingredients (APIs),

manufacturing and packaging of bulk materials, manufacturing and packaging of finished

pharmaceutical products (FPPs) and/or performing analytical testing.

本 指南适用于原料药生产活动、散装物料的生产和包装、制剂成品和

/

或的生产和包装、分析所用的

检验方法。

2.3 The recommendations provided in these guidelines apply to all dosage forms but need to be

adjusted on a case-by-case basis (e.g. by using risk management principles). Particularly close

control of certain aspects will be required for certain formulations such as sterile products, and

metered dose aerosols. WHO guidance on manufacture of specific pharmaceutical

products

(4,5)

will be useful in this regard.

本指南中的推荐适用于所有剂型，但需要根据具体案例进行调整（例如 采用风险管理原则）。对某些

特殊剂型，例如无菌产品、单剂量气溶胶进行特殊控制。< /p>

WHO

对特殊药品的生产指南（

4.5< /p>

）对此会

有指导作用。

2.4 The guidelines address the following areas at the SU and the RU:

—

transfer of development and production (processing, packaging and cleaning);

—

研发和生产转移（工艺、包装和清洁）

—

transfer of analytical methods for quality assurance and quality control;

—

质量保证和质量控制的分析方法转移

—

skills assessment and training;

—

技能评价和培训

—

organization and management of the transfer;

—

转移的组织和管理

—

assessment of premises and equipment;

—

前提和设备评价

—

documentation; and

—

文件，和

—

qualification and validation.

—

确认和验证

2.5 Because each transfer project is unique, the provision of a comprehensive set of guidelines is

beyond the scope of this document.

由于每个技术转移项目都是独特的，本文件并不提供一个综合性的 整套指南条款。

2.6 These guidelines do not provide guidance on any legal, financial or commercial considerations

associated with technology transfer projects.

这些指南并不提供与技术转移项目相关的任何法律、财务或商业方 面的考虑。

3.

Glossary

术语

The definitions given below apply to the terms used in these guidelines.

以下给出的术语定义仅限用于本指南中。

They may have different meanings in other contexts.

在其它上下文中可能有不同的含义。

acceptance criteria

可接受标准

Measurable terms under which a test result will be considered acceptable.

一个可以测量的标准，符合这个标准时检测结果被认为是可以 接受的。

active pharmaceutical ingredient (API)

活性药物成份（原料药）

Any substance or mixture of substances intended to be used in the manufacture of a

pharmaceutical dosage form and that, when so used, becomes an active ingredient of that

pharmaceutical dosage form. Such substances are intended to furnish pharmacological activity or

other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect

the structure and function of the body.

任何物 质或混合物，

用于药品制剂的生产，

成为这个制剂的一种活性成 份。

这种物质用于产生生物学

活性，或用于治愈、缓解、治疗， 或防止疾病，影响人体结构和功能。

Bracketing

正交

An experimental design to test only the extremes of, for example, dosage strength. The design

assumes that the extremes will be representative of all the samples between the extremes.

一种试验设计方法。用来检查，例如，剂量的极限。设计假定上下 极限能代表极限之间的所有样品。

change control (C/C)

变更控制

A formal system by which qualified representatives of appropriate disciplines review proposed or

actual changes that might affect a validated status. The intent is to determine the need for action

that would ensure that the system is maintained in a validated state.

一个正式的体系，

根据这个体系，

有资质相关 学科的代表对建议的或实际的，

可能会对验证过的状态

产生影响 的变更进行审核。

变更控制的目的是决定是否需要采取行动来保证体系维持在被验证的状 态。

Commissioning

调试

The setting up, adjustment and testing of equipment or a system to ensure that it meets all the

requirements, as specified in the user requirement specification, and capacities as specified by the

designer or developer. Commissioning is carried out before qualification and validation.

对设备或一个系统进行设置、

调整和检测，

以保证其符合在用户需求手册中列出的所有要求，

以及由

设计者或研发人员所指定的能力。调试应在确认和验证之前实施。

control strategy

控制策略

A planned set of controls, derived from current product and process understanding, that assures

process performance and product quality. The controls can include parameters and attributes

related to materials and components related to drug substances and drug product materials and

components, facility and equipment operating conditions, in- process controls, finished product

specifications, and the associated methods and frequency of monitoring and control (

6

).

一个计划的控制系列，

它来自于现行产品和对工艺的理解，

它保证工艺性能和产品质量。< /p>

控制可以包

括与参数和原料属性，以及与原料药有关的组件、制剂 原料和组件、设施和设备操作条件、中控、成

品质量标准、相关的检验方法和监控的频次 。

corrective action (C/A)

纠正措施

Any action to be taken when the results of monitoring at a critical control point indicate a loss of

control.

当对关键控制点的监控显示其失控时将要采取的任何措施。

Critical

关键

Having the potential to impact on product quality or performance in a significant way.

会显著影响产品质量或性能的潜在可能性。

critical control point (CCP)

关键控制点

A step at which control can be applied and is essential to prevent or eliminate a pharmaceutical

quality hazard or to reduce it to an acceptable level.

一个步骤，

通过控制这 个步骤可以从根本上阻止或消除对药品质量的危害，

或将其降低到可以接受的