WHO第961号技术报告_附件7_药物生产技术转移指南(中英文)

WHO第961号技术报告附件7 药物生产技术转移指南
World Health Organization
WHO Technical Report Series，No. 961, 2011
WHO第961号技术报告附件7 药物生产技术转移指南
Annex 7 附件7
WHO guidelines on transfer of technology in pharmaceutical manufacturing
WHO药物生产技术转移指南
1. Introduction 介绍
2。

Scope 范围
3。

Glossary 术语
4. Organization and management 组织和管理
5。

Production：transfer （processing, packaging and cleaning）生产：转移(工艺、包装和清洁）
6. Quality control: analytical method transfer质量控制：分析方法转移
7. Premises and equipment 厂房设施和设备
8. Documentation 文件
9。

Qualification and validation 确认和验证
References 参考文献
1. Introduction 介绍
These guiding principles on transfer of technology are intended to serve as a framework which can be applied in a flexible manner rather than as strict rigid guidance. Focus has been placed on the quality aspects，in line with WHO’s mandate.
本指南中关于技术转移的原则意在作为一个框架，以不同方式应用,而不是一个需要严格遵守的指南。

指南重点在于质量方面，与WHO的任务一致。

1。

1 Transfer of processes to an alternative site occurs at some stage in the life-cycle of most products, from development，scale-up，manufacturing, production and launch，to the
post-approval phase.
将工艺转移至一个可替代的场所发生在大多数产品的生命周期的某些阶段，从研发、放大、生产、到上市后阶段。

1。

2 Transfer of technology is defined as “a logical procedure that controls the transfer of any process together with its documentation and professional expertise between development and manufacture or between manufacture sites"。

It is a systematic procedure that is followed in order to pass the documented knowledge and experience gained during development and or commercialization to an appropriate, responsible and authorized party。

技术转移被定义为“控制研发方和生产方，或两个生产场所之间所有工艺文件和专业技术转移的逻辑程序”。

技术转移是一个系统性的程序，遵守该程序是为了能将在研发过程中已记录的知识和经验转移给一个适当的，承担责任的经过授权的主体方。

Technology transfer embodies both the transfer of documentation and the demonstrated ability of the receiving unit (RU）to effectively perform the critical elements of the transferred technology, to the satisfaction of all parties and any applicable regulatory bodies.
技术转移包括文件转移和接收单位的重现能力，以使用得转移技术的关键要素得以有效实施,满足参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（I）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。

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；
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。

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、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 intraor intersite 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。

WHO对特殊药品的生产指南（4。

5）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。

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水平。

design qualifi cation （DQ) 设计确认
Documented evidence that the premises, supporting systems，utilities, equipment and processes have been designed in accordance with the requirements of good manufacturing practices （GMP）. 文件化的证据，证明设施、支持系统、公用系统、设备和工艺已经根据GMP要求进行设计. design space 设计空间
The multidimensional combination and interaction of input variables (e。

g。

material attributes）and process parameters that have been demonstrated to provide assurance of quality （7）.
多维组合和输入变量（例如原料属性）与工艺参数的互动，其已被证明可以保证产品质量（7）.
drug master file (DMF）药物主文件
Detailed information concerning a specific facility，process or product submitted to the medicines regulatory authority, intended for incorporation into the application for marketing authorization。

某个公用系统、工艺或产品的详细信息,它被申报给药品法规当局，用于支持制剂的上市批准申请.
finished pharmaceutical product （FPP）成品药
A product that has undergone all stages of production, including packaging in its fi nal container and labelling。

An FPP may contain one or more APIs.
一个经过了生产的所有环节，包括最终包装和贴标签的产品.一种成品药可能包含一种或多种原料药.
gap analysis 差异分析
Identification of critical elements of a process which are available at the SU but are missing from the RU。

识别在转出方有，但接收方没有的关键工艺要素。

good manufacturing practices （GMP) 优良制造规范
That part of quality assurance which ensures that pharmaceutical products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization （3）。

质量保证的一部分，用以保证药品被持续生产和控制,达到既定使用目的所需的质量标准,符合上市许可要求.
in-process control （IPC) 中间控制
Checks performed during production in order to monitor and, if necessary，to adjust the process to ensure that the product conforms to its specifications。

The control of the environment or equipment may also be regarded as a part of in-process control。

在生产过程中实施的检查，用以监控和，必要时调查工艺以保证产品符合其质量标准.环境控制或设备控制也可以认为是中控的一部分.
installation qualification （IQ）安装确认
The performance of tests to ensure that the installations （such as machines, measuring devices，utilities and manufacturing areas) used in a manufacturing process are appropriately selected and correctly installed and operate in accordance with established specifications.
对生产工艺中所使用的（例如机器、计量装置、公用系统和生产区域)安装进行的测试，以保证其选择是适当的，安装是正确的，并可以按既定的标准进行操作。

intercompany transfer 公司间转移
A transfer of technology between sites of different companies.
在不同公司的工厂间进行的技术转移.
intracompany transfer 公司内转移
A transfer of technology between sites of the same group of companies。

在公司同一集团内工厂间进行的技术转移.
operational qualification (OQ) 运行确认
Documented verification that the system or subsystem performs as intended over all anticipated operating ranges。

系统或子系统在需要的操作范围内进行运行的确认及其记录
performance qualifi cation (PQ) 性能确认
Documented verification that the equipment or system operates consistently and gives reproducibility within defined specifications and parameters for prolonged periods。

(In the context of systems，the term “process validation” may also be used。

）
证明设备或系统能持续运行，能在延长的时间内重复实现既定的质量标准和参数的确认性文件。

（在讨论系统时，可能会使用术语“工艺验证")
process validation 工艺验证
Documented evidence which provides a high degree of assurance that a specific process will consistently result in a product that meets its predetermined specifications and quality characteristics.
证明某工艺能持续稳定生产出符合既定质量标准和质量特性的文件和记录。

qualification 确认
Action of proving and documenting that any premises, systems and equipment are properly installed，and/or work correctly and lead to the expected results. Qualification is often a part (the initial stage）of validation，but the individual qualification steps alone do not constitute process validation。

证明和记录所有设施、系统和设备已适当安装，和/或正确运行,能达到期望的结果的动作.确认通常是验证的一部分(初始阶段）,但单个验证步骤不能形成工艺验证。

qualification batches 确认批次
Those batches produced by the RU to demonstrate its ability to reproduce the product (1)。

由接收单位生产的,证明其具备生产能力的批次（1）。

quality assurance (QA）质量保证
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 objective of ensuring that pharmaceutical products are of the quality required for their intended use.
质量保证是一个宽范畴的概念，涵盖所有单独或整体对产品质量造成影响的情况。

它是保证药品具有其用途所需的品质所做的所有安排的总和.
quality control （QC) 质量控制
Quality control covers all measures taken，including the setting of specifications，sampling，testing and analytical clearance，to ensure that starting materials, intermediates，packaging materials and finished pharmaceutical products conform with established specifications for identity, strength, purity and other characteristics.
质量控制包括采取的所有措施,包括设定质量标准、取样、检测和分析清场，以保证起始物料、中间体、包材和制剂成品与所建立的均一性、剂量、纯度和其它特性相符合.
quality planning质量计划
Part of quality management focused on setting quality objectives and specifying necessary operational processes and related resources to fulfil the quality objectives (6）。

质量管理的一部分,重点关注质量目标的设置，指出必要的操作流程，和满足质量目标所需的资源（6）。

quality policy 质量方针
Overall intentions and direction of an organization related to quality as formally expressed by senior management （6）。

高层管理人员正式表达的与质量相关的组织目的和全面意图(6)。

quality risk management （QRM）质量风险管理
Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the pharmaceutical product throughout the product life—cycle.
质量风险管理是药品生命周期中对质量风险进行评估、控制、沟通和回顾的一个系统性过程。

receiving unit (RU）接收单位
The involved disciplines at an organization where a designated product, process or method is expected to be transferred。

接收被转移产品、工艺或方法所涉及的组织单位。

sending unit （SU)转出单位
The involved disciplines at an organization from where a designated product, process or method is expected to be transferred。

将被转移产品、工艺或方法转移出去所涉及的组织单位。

Spiking 加样
The addition of a known amount of a compound to a standard，sample or placebo，typically for the purpose of confirming the performance of an analytical procedure。

他们标准品、样品或空白样品中加入已知数量化合物，典型地应用于确认分析方法的性能。

standard operating procedure （SOP) 标准操作规程
An authorized written procedure giving instructions for performing operations not necessarily specific to a given product or material （e.g。

equipment operation, maintenance and cleaning, validation, cleaning of premises and environmental control，sampling and inspection)。

Certain SOPs may be used to supplement product—specific master and batch production documentation。

批准的书面程序,在其中给出非产品或物料专用的操作指令（例如设备操作、维护和清洁、验证、设施清洁、环境控制、取样和检查）。

特定的SOP可能用于对特定产品工艺规程和批生产文件进行补充.
technology transfer report 技术转移报告
A documented summary of a specific technology transfer project listing procedures，acceptance criteria, results achieved and conclusions. Any deviation should be discussed and justified.
将特定的技术转移项目程序、可接受标准、达到的结果和结论进行汇总的文件。

所有偏差均应有讨论和判定.
Validation验证
Action of proving and documenting that any process, procedure or method actually and consistently leads to the expected results.
证明并记录所有工艺、程序或方法可以实际地获得一致的期望结果的动作.
validation master plan (VMP）验证主计划
A high—level document that establishes an umbrella validation plan for the entire project and summarizes the manufacturer’s overal l philosophy and approach, to be used for establishing performance adequacy。

It provides information on the manufacturer’s validation work programme and defines details of and timescales for the validation work to be performed, including a statement of the responsibilities of those implementing the plan.
高层次文件,在其中对一个完整的项目建立一个总体验证计划，并总结生产商的总体验证理念和验证方法，以达到要求的效率。

它提供生产商验证工作程序、验证工作时间表、实施人员职责等信息.
validation protocol (or plan）（VP) 验证方案（或计划）
A document describing the activities to be performed in a validation, including the acceptance criteria for the approval of a manufacturing process - or a part thereof - for routine use.
描述在验证需要实施的活动的文件,包括批准一个生产工艺———--或其中一部分--———-常规使用
的可接受标准。

validation report (VR）验证报告
A document in which the records，results and evaluation of a completed validation programme are assembled and summarized。

It may also contain proposals for the improvement of processes and or equipment.
包括完整的验证过程的记录、结果和评估整理和总结的文件。

也可以包括工艺和/或设备的改进方案。

4. Organization and management 组织和管理
4.1 Transfer comprises an SU and an RU. In some circumstances there may be an additional unit which will be responsible for directing，managing and approving the transfer。

转移包括一个转出方和一个接收方。

在有些环境下，可能会有更多单位参与指挥、管理和批准转移.
4.2 There is a formal agreement between the parties，which specifies the responsibilities before, during and after transfer.
双方应该有一个正式的协议，在其中说明在转移前、转移中、转移后的责任。

4。

3 Organization and management of a successful technology transfer need to ensure that the main steps have been executed and documented as described in section 1.6.
成功的技术转移组织和管理需要保证主要步骤进行实施，并如1。

6部分要求进行记录.
4。

4 There should be a project management plan which identifies and controls all the necessary activities identified at the start of the undertaking。

应该有一个项目管理计划，在其中对开始时界定的一些必要的活动进行识别和控制.
4。

5 The transfer protocol should list the intended sequential stages of the transfer。

The protocol should include：
转移方案应按顺序列出转移步骤。

方案应包括
-objective; 目的
—scope; 范围
—key personnel and their responsibilities; 关键人员及其职责
- a parallel comparison of materials，methods and equipment; 原料、方法和设备的平行比较—the transfer stages with documented evidence that each critical stage has been satisfactorily accomplished before the next commences；转移各步骤均应有书面证据证明每个关键步骤圆满完成后,方可进入下一步骤
-identification of critical control points; 关键控制点的识别
—experimental design and acceptance criteria for analytical methods; 实验设计和分析方法的可接受标准
—information on trial production batches，qualification batches and process validation；试生产批次的信息，确认批次和工艺验证
-change control for any process deviations encountered；任何遇到的工艺偏差的变更控制—assessment of end—product；终成品的评价
-arrangements for keeping retention samples of active ingredients，intermediates and finished products，and information on reference substances where applicable; and 活性成份、中间体和制剂的留样的安排，适用时，对照品的信息，以及
—conclusion，including signed-off approval by project manager。

结论，包括项目经理批准的签字
4。

6 The SU should provide the necessary validation documentation for the process and its support functions。

Usually, an established process is transferred, and such documentation is already available.
转出方应提供必要的工艺验证文件，及其支持的功能。

一般转移的工艺应该已建立好，这些文件应都是可以获得的。

4.7 The SU should provide criteria and information on hazards and critical steps associated with the product, process or method to be transferred，to serve as a basis for a quality risk management （QRM) exercise at the RU （7–10)。

转出方应提供与将要转移的产品、工艺或方法相关的安全标准和信息,以及关键步骤，作为接收方进行质量风险管理的基础（QRM).
4。

8 The SU or third party should assess the suitability and degree of preparedness of the RU before transfer，with regard to premises, equipment and support services (e。

g。

purchasing and inventory control mechanisms，quality control (QC）procedures, documentation, computer validation，site validation, equipment qualification，water for pharmaceutical production and waste management）。

转出方或第三方应在转移前对接收方准备情况进行评估，评估应包括基础设施、设备和支持性服务（例如采购和库存控制机制、质量控制（QC）程序、文件记录、计算验证、厂房验证、设备确认、制药用水、废物管理).
4。

9 The SU and the RU should jointly verify that the following，satisfactorily completed，validation protocols are available：
转出方和接收方应联合确认以下内容圆满完成，验证方案已完成
●installation qualification （IQ）and operational qualification (OQ）data for manufacturing
and packaging equipment at the RU site and analytical equipment；and
●接收方工厂生产和包装设备、检验设施安装确认和运行确认数据，以及
●qualification of the rooms for both manufacture and packaging at the RU site。

接受单位生产
和包装房间确认
4。

10 The SU and the RU should jointly implement any training programmes that may be required specific to the product, process or method to be transferred, e.g。

on analytical methods or equipment usage，and assess training outcomes.
转出方和接收方应联合实施所有可能需要的与要转移的产品、工艺或方法相关的培训项目，例如分析方法或设备使用，并对培训效果进行评估。

4。

11 The SU and the RU should jointly execute the transfer protocol according to a checklist and or flow diagram showing the sequence of steps to be carried out to effect an efficient transfer.
转出方和接收方应根据表现步骤顺序的检查清单和/或流程图联合实施转移方案,这些步骤的实施顺序可能会影响到转移的效率。

4。

12 Any changes and adaptations made during the course of the technology transfer should be fully documented.
所有在技术转移过程中进行的变更均应进行记录。

4.13 The SU and the RU should jointly document the execution of the transfer protocol in a transfer of technology summary in a report。

转出方和接收方应一起记录对转移方案的实施，在报告中记录技术转移总结.
Project team 项目组
4.14 Any transfer project will be managed by a team comprising members with clearly defined key responsibilities. The team should be drawn from members of relevant disciplines from both the SU and RU sites.
所有转移项目应由项目组管理，项目组人员主要职责均应明确。

项目组应从转出方和接收方相关学科人员中选出。

4.15 The team members should have the necessary qualifications and experience to manage their particular aspect of the transfer.
项目组成员应具备必要的资质和经验，以管理转移中的不同方面。

5。

Production: transfer （processing, packaging and cleaning) 生产：转移(工艺、包装和清洁)
5。

1 The RU should be able to accommodate the intended production capacity. If possible，it should be established at the outset whether the intention is to perform single-batch manufacture，continuous production or campaigns。

接收方应提出想要的生产规模.可能时,应在开始时即决定是单批生产、连续生产还是周期生产模式。

5.2 Consideration should be given to the level and depth of detail to be transferred to support production and any further process development and optimization at the RU as intended under the transfer project plan。

要考虑能支持接收方的生产、所有进一步工艺研发、接收方优化工艺所需的转移的详细程度。

5.3 Consideration should be given to the technical expertise, site technology and site capabilities for the RU。

It should be identified upfront by the SU of any process robustness issues so that plans may be put in place at the RU.
需要考虑接收方的技术专业能力、场所技术和场所产能.转出方应识别出工艺耐用性，这样接收方可以制订计划。

5。

4 The SU and the RU should jointly develop a protocol for the transfer of relevant information related to the process under consideration from the SU to the RU, as well as the development of a comparable process at the RU。

转出方和接收方应基于共同考虑,一起制订一份针对与工艺转移相关信息的方案,以及接收方研发可比性工艺的信息.
Starting materials 起始物料
5。

5 The specifications and relevant functional characteristics of the starting materials （APIs and excipients）(11，12) to be used at the RU should be consistent with materials used at the SU。

Any properties which are likely to influence the process or product should be identified and characterized。

接收方会用作起始物料（原料药或辅料（11。

12））的质量标准和相关功能性特性应与转出方所用的一致。

所有可能会对工艺或产品产生影响的特性均应进行识别和描述。

Active pharmaceutical ingredients （API) 活性药物成分（原料药）
5.6 The SU should provide the RU with the open (applicant’s）part of the API master file （APIMF or drug master file （DMF）or active substance master file (ASMF))，or equivalent information and any relevant additional information on the API of importance for the manufacture of the pharmaceutical product。

The following are examples of the information which may typically be provided；however the information needed in each specific case should be assessed using the principles of QRM:
转出方应向接收方提供原料药药物主文件（APIMF或DMF或ASMF）公开部分,或等同的信息，对制剂生产具有重要意义的原料药的其它相关信息，在每个单独的个案中，应采用质量风险管理的原则对所需要的信息进行评估：
●manufacturer and associated supply chain；
●生产商和相关的供应链
●step of the API to be transferred;
●将要转移的原料药的步骤
●flow chart of synthesis pathway，outlining the process，including entry points for raw
materials，critical steps, process controls and intermediates；
●合成路线流程图，合成概述，包括原料加入点,关键步骤，工艺控制和中间体
●where relevant，definitive physical form of the API （including photomicrographs and other
relevant data）and any polymorphic and solvate forms；
●适用时,原料药的最终物理形态（包括显微图片和其它相关的数据）和所有晶型和溶剂化形态●solubility profile；。