重磅分享！WHO《制药生产技术转移指南》（中英文对照版）！

7、给出分析方法转移过程中可能的实验设计和接受标准：

全文翻译如下：

WHO guidelines on the transfer of technologyin pharmaceutical manufacturing

WHO制药生产技术转移指南

Background

背景

1. Introduction

介绍

2. Scope

范围

3. Glossary

术语

4. Due diligence and gap assessments

尽职调查和差距评估

5. Organization and management

组织和管理

6. Quality management and quality risk management

质量管理和质量风险管理

7. Documentation

文件

8. Premises

厂房

9. Equipment and instruments

设备和仪器

10. Qualification and validation

确认与验证

11. Product life cycle and project management principles

产品生命周期和项目管理原则

12. Phases of a technology transfer project

技术转移项目阶段

Phase I: Project initiation

阶段1 ：项目启动

Phase II: Project proposal

阶段2 ：项目计划

Phase III: Project transfer

阶段3 项目转移

Phase IV: Project review

阶段4 ：项目回顾

References

参考文献

Further reading

拓展阅读

Abbreviations

缩略语

Appendix 1. Example of documentation commonly required for the transferof technology

附录1. 技术转移通常需要的文件示例

Appendix 2. Example of possible experimental designs and acceptancecriteria for analytical testing

附录2. 分析测试可能的实验设计和接受标准示例

1. Introduction

介绍

1.1. Production and control procedures, validation and otherrelated activities may be transferred from one site to another site prior toobtaining a marketing authorization. In some cases, this transfer takes placeafter the approval of, for example, a product, by a regulatory authority. Thistransfer can be, for example, from drug discovery to product development; toclinical trials; or to full-scale commercialization and commercial batchmanufacturing; cleaning and validation.

在获得上市许可之前，生产和控制程序、验证和其他相关活动可能从一个场所转移到另一个查场所。在某些情况下，这种转移在产品获得监管机构的批准后也会进行。这种转移可以是，例如，从药物发现到产品开发；到临床试验；或到全面商业化和商业化批量生产；清洁和验证。

1.2. A technology transfer, particularly one between differentcompanies, has legal and economic implications. If such issues, which mayinclude intellectual property rights, royalties, pricing, conflicts of interestand confidentiality agreements, are expected to impact on the open communicationof technical matters in any way, they should therefore be addressed before andduring the planning and execution of the transfer.

技术转移，特别是不同公司之间的技术转移，具有法律和经济意义。如果这些问题(可能包括知识产权、诚信、价格、利益冲突和保密协议)预计会以任何方式影响技术事项的公开沟通，则应在转移计划和执行之前和期间予以解决。

1.3. A technology transfer requires aplanned approach by trained, knowledgeable personnel working within a qualitysystem, with documentation, data and information covering all aspects ofdevelopment, production and quality control (QC), as applicable.

技术转移需要由经过培训的具备丰富知识并在质量体系内工作的人员进行规划，并有包含所有开发、 生产和质量控制（QC）（如适用）的文件记录、数据和信息。

1.4. A technology transfer takes placebetween a sending unit (SU) and a receiving unit (RU). In some cases, there maybe a separate unit managing the project.

技术转移发生在转移方（SU）和接收方（RU）之间。有时可能会有一个单独的部门来管理该项目。

1.5. The technology transfer projectshould fulfil the following general principles and requirements.

技术转移项目应满足以下通用原则和要求：

There should be:

应有：

1.6. A technology transfer should includerelevant documentation, data, information and knowledge from the SU in order toenable the RU to effectively perform the specified process or procedure in, forexample, production and QC. A successful transfer of technology should resultin proof that the RU can routinely reproduce the transferred product, processor procedure against a predefined set of specifications as agreed between theSU and RU.

技术转移应包括来自转移方的相关文件、数据、信息和知识，使得接收方能够有效实施指定的工艺或方法，例如生产和 QC。成功的技术转移应证明接收方可以常规化地按转移方与接收方之间预定的标准生产出所转移的产品、工艺或方法。

1.7. This document should be read inconjunction with other WHO guidelines as referenced below (2-14), as well asother regulatory guidelines which include The International Council for Harmonisationof Technical Requirements for Pharmaceuticals for Human Use (ICH) Q7, Q8, Q9,Q10 and Q11. This guideline does not intend to replace any of these guidelines.

本文应与参考文献 2-4 所列其它 WHO 指南，以及其它法规指南一起阅读，其中包括ICHQ7、 Q8、 Q9、 Q10 和 Q11。本指南无意取代这些指南。

1.8. This version of the guidelineprovides updated requirements and expectations reflecting current goodpractices (GxP) in the transfer of technology and replaces the previous versionpublished (1).

本版指南对要求和期望进行了更新，从而反映对技术转移的现行 GXP 要求，取代之前发布的版本。

2. Scope

范围

2.1. This document provides guidingprinciples on technology transfer.

本文提供了技术转移的指导原则。

2.2. This guideline should be applied whentransferring the technology of processes and procedures relating to activepharmaceutical ingredients (APIs), in-process bulk materials, finishedpharmaceutical products (FPPs), process validation, cleaning procedure developmentand validation and analytical procedures.

本指南应用于与 API、制剂中间体、制剂成品（FPP）、工艺验证、清洁程序开发和验证以及分析方法有关的工艺和方法技术转移。

2.3. The guideline applies to all pharmaceuticaldosage forms and may be adapted on a caseby- case basis by using riskmanagement principles. Particular attention should be given to certain complexformulations such as, for example, sterile products and metered dose aerosols.

本指南适用于所有制剂形式，可采用风险管理原则根据各案进行调整。应特别注意特定的复杂制剂，如无菌产品和定量气雾剂。

2.4. Although this document focuses onpharmaceutical products, the principles can also be applied to the transfer ofproduction, related processes and controls for other products such as biopharmaceuticalproducts, vaccines, medical devices and vector control products.

虽然本文重点在于药品，但其原则应可应用于其它产品如生物制品、疫苗、医疗器械和病媒控制产品的生产、相关工艺和控制的转移。

2.5. Because eachtransfer project is unique, the provision of a comprehensive set of guidelines specificto a product or process is beyond the scope of this document.

因为每个转移项目都是唯一的，对某一产品或工艺给出全面系列的指南条款并不在本文范围内。

2.6. This document does not provide guidance on anylegal, financial or commercial considerations associated with technology transferprojects.

本文件并不提供技术转移项目有关的任何法律、金融或商业方面考量。

2.7.This document addresses the following principal areas:

本文涉及以下主要方面：

3.Glossary

术语

Thedefinitions given below apply to the terms used in these guidelines. They havebeen aligned as far as possible with the terminology in related WHO guidelinesand Good Practices and included in the WHO QualityAssurance of Medicines Terminology Database - List of Terms and relatedguideline https://www.who.int/docs/default-source/medicines/norms-andstandards/guidelines/mqa-terminology-sept-2020.pdf?sfvrsn=48461cfc_5 ), but mayhave different meanings in other contexts.

以下定义适用于本指南中所用术语。它们目前为止已尽可能与WHO 药品质量保证术语数据库中相关 WHO指南和优良规范及保持一致，但在其它语境中可能会有所不同。

acceptance criteria.

可接受标准

Measurable terms under which a test result will beconsidered acceptable.

测试结果被认为是可接受的可测量项。

active pharmaceutical ingredient (API).

活性药物成分 （API）

Any substance or mixture of substances intended to beused in the manufacture of a pharmaceutical dosage form and that, when so used,becomes an active ingredient of that pharmaceutical dosage form. Suchsubstances are intended to furnish pharmacological activity or other directeffect in the diagnosis, cure, mitigation, treatment or prevention of disease,or to affect the structure and function of the body.

准备用于制剂生产成为其中活性成分的物质或其混合物。此类物质用于改变 药效活性或其它直接影响诊断、治愈、缓解、治疗或预防疾病影响或影响人体结构和功能。

ALCOA+.

A commonly used acronym for “attributable, legible,contemporaneous, original and accurate that puts additional emphasis on theattributes of being complete, consistent, enduring and available – implicitbasic ALCOA principles.

常用术语，代表“可归属、清晰、同步、原始和准确”， +号表示完整性、一致性、持久性和可及性—基本 ALCOA 原则的暗含意思

bracketing.

括号法

An experimental design to test the extremes of, forexample, dosage strength. The design assumes that the extremes will berepresentative of all the samples between the extremes.

对，例如剂量，的极端情况进行检测的实验设计。该设计假定极端情况代表了其所涵盖的所有样本。

change control.

变更控制

A formal system by which qualified representatives ofappropriate disciplines review proposed or actual changes that might affect avalidated status. The intent is to determine the need for action that wouldensure that the system is maintained in a validated state.

由某个学科具备资质的代表审核可能影响已验证状态的所拟或实际变更的正式系统，旨在确定是否需要采取措施确保系统维持在已验证的状态。

control strategy.

控制策略

A planned set of controls, derived from current productand process understanding that assures process performance and product quality.The controls can include parameters and attributes related to API and finishedpharmaceutical product materials and components, facility and equipmentoperating conditions, in-process controls, finished product specifications andthe associated methods and frequency of monitoring and control.

来自当前产品和工艺理解的经过规划的一系列控制，可确保工艺性能和产品质量。这些控制措施可包括 API 和制剂物料和组份有关的参数和属性、设施和设备操作条件、中控、成品标准和相关方法与监测和控制频次。

corrective action.

纠正措施

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

当关键控制点的监测结果显示失控时准备采取的措施

critical.

关键

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

可能对产品质量或性能有重大影响者

critical control point.

关键控制点

A step at which control can be applied and is essentialto prevent or eliminate a pharmaceutical quality hazard or to reduce it to anacceptable level.

可进行控制防止或消除一个药品质量危害或将其降低至可接受水平的步骤

design qualification.

设计确认

Documented evidence that, for example, the premises,supporting systems, utilities, equipment and processes have been designed inaccordance with the requirements of good manufacturing practices (GMP).

证明例如设施、支持系统、公用系统、设备和工艺的设计符合 GMP 要求的书面证据

design space.

设计空间

The multidimensional combination and interaction of inputvariables (e.g. material attributes) and process parameters that have beendemonstrated to provide assurance of quality

输入变量（例如物料属性）的多维度组合和相互作用以及被证明可保证药品质量的工艺参数

drug master file.

药物主文件

Detailed information concerning a specific facility,process or product submitted to the medicines regulatory authority, intendedfor incorporation into the application for marketing authorization.

向药监机构提交的关于某个场所、工艺或产品的详细信息，意在将其结合至上市许可申报资料中。

finished pharmaceutical product (FPP).

制剂成品（FPP）

A product that has undergone all stages of production,including packaging in its final container and labelling. An FPP may containone or more active pharmaceutical ingredients (APIs).

经过了所有生产步骤包括包装在最终容器中并贴上标签的产品。一种 FPP 可包括一种或多种 API

gap analysis.

差距分析

The identification of the critical elements of a processwhich are available at the sending unit (SU) but are missing from the receivingunit (RU).

good manufacturing practices (GMP).

良好生产规范 （GMP）

That part of quality assurance which ensures thatpharmaceutical products are consistently produced and controlled to the qualitystandards appropriate to their intended use and as required by the marketingauthorization.

质量保证中确保药品被持续生产和检测达到其既定用途所需的合适质量标准并符合上市许可要求的一部分

in-process control (IPC).

中间控制（IPC）

Checks performed during production in order to monitorand, if necessary, to adjust the process to ensure that the product conforms toits specifications. The control of the environment or equipment may also beregarded as a part of in-process control.

在生产期间执行的检查，以监测和（必要时）调整工艺从而确保产品符合其标准。环境或设备的控制可能亦可作为中间控制的一部分。

installation qualification (IQ).

安装确认（IQ）

Documented verification that the installations (such asmachines equipment and instruments, computer system components, measuringdevices, utilities and manufacturing) used in a processor system areappropriately selected and correctly installed, in accordance with establishedspecifications.

证明工艺或系统所用装置（如机器、设备和仪器、计算机系统组件、测量装 置、公用系统和生产）根据既定标准经过恰当选择，正确安装的文件化工 作。

intercompany transfer.

公司间转移

A transfer of technology between the sites of differentcompanies.

不同公司的场所之间的技术转移

intracompany transfer.

公司内转移

A transfer of technology between sites of the same groupof companies.

同一集团公司之间的技术转移

operational qualification (OQ).

运行确认（OQ）

Documented verification that the system or subsystemperforms as intended over all anticipated operating ranges.

证明系统或子系统按既定预期运行范围运行的文件化工作。

performance qualification (PQ).

性能确认（PQ）

Documented verification that the equipment or systemperforms

consistently and reproducibly within definedspecifications and parameters in its normal operating environment (i.e. in theproduction environment).

证明设备或系统性能在正常操作环境下（即生产环境下）持续重复满足既定 标准和参数的文件化工作。

process validation.

工艺验证

The collection and evaluation of data, from the processdesign stage through to commercial production, which establishes scientificevidence that a process is capable of continuously delivering the finishedpharmaceutical product meeting its predetermined specifications and qualityattributes.

从工艺设计阶段到商业化生产过程中建立科学证据证明工艺有能力持续生产 出满足既定标准和质量属性的数据集合与评估

qualification.

确认

Documented evidence that premises, systems or equipmentare able to achieve the predetermined specifications when properly installed,and/or work correctly and lead to the expected results.

证明设施、系统或设备经过恰当安装和/或正确运行并得到预期结果，有能力 达到既定标准的文件化证明

qualification batches.

确认批

Those batches produced by the receiving unit (RU) todemonstrate its ability to reproduce the product .

由接收方生产证明其有能力生产该产品的批次

quality assurance (QA).

质量保证（QA）

“Quality assurance” is a wide-ranging concept coveringall matters that individually or collectively influence the quality of aproduct. It is the totality of the arrangements made with the objective ofensuring that pharmaceutical products are of the quality required for theirintended use.

“质量保证”是一个很宽的概念，它包括单独或一起影响产品质量的所有方面。它是为了确保药品具备其既定用途所需质量的而做的所有工作。

quality control (QC).

质量控制（QC）

All measures taken, including the setting of specifications, sampling, testing and analytical clearance, to ensure thatstarting materials, intermediates, packaging materials and finishedpharmaceutical products (FPP) conform with established specifications foridentity, strength, purity and other characteristics.

为确保起始物料、中间体、包材和成品（FPP）符合既定的鉴别、含量、纯 度和其它属性标准所执行的所有工作，包括设置标准、取样、检测和分析清场

quality planning.

质量计划

Part of quality management, focused on setting qualityobjectives and specifying necessary operational processes and related resourcesto fulfil the quality objectives.

质量管理的一部分，主要是设置质量目标和指定必要的操作流程和相关的资源以达成质量目标

quality policy.

质量方针

A brief statement that describes the organization’spurpose, overall intentions and strategic direction; provides a framework forquality objectives; and includes a commitment to meet applicable requirements.

说明公司的目的、全面目标和策略方向，表达质量目标框架，包括承诺满足 适用要求的简要声明

quality risk management (QRM).

质量风险管理 （QRM）

A systematic process for the assessment, control,communication and review of risks to the quality of the pharmaceutical productthroughout the product’s life cycle.

贯穿药品整个生命周期的质量风险评估、控制、沟通和回顾系统化流程

receiving unit (RU).

接收方（RU）

The involved disciplines at an organization where adesignated product, process or method is expected to be transferred.

准备接收所转移产品、工艺或方法的一方

sending unit (SU).

转移方（SU）

The involved disciplines at an organization from where adesignated product, process or method is expected to be transferred.

准备转出产品、工艺或方法的一方

standard operating procedure (SOP).

标准操作规程（SOP）

An authorized written procedure giving instructions forperforming operations, not necessarily specific to a given product or material, but of a more general nature (for example, operation of equipment,maintenance and cleaning, validation, cleaning of premises and environmentalcontrol, sampling and inspection). Certain standard operating procedures may beused to supplement product-specific master and batch production documentation.

经过批准的程序，给出执行操作的指令，不一定是某个具体的产品或物料， 可能是更为通用的（例如设备的操作、维护和清洁、设施的验证和清洁、环 境控制、取样和检查）。特定的标准操作规程可能会被用于补充产品专用的主生产文件和批生产文件

transfer of technology.

技术转移

A logical procedure that controls the transfer of anyprocess, together with its documentation and professional expertise betweendevelopment and manufacture or between manufacture sites. It is a systematicprocedure that is followed in order to pass the documented knowledge andexperience gained during development and/or commercialization to anappropriate, responsible and authorized party.

控制工艺及其文件和专业知识在开发方与生产方或在不同生产场所之间进行 转移的逻辑程序。它是一个系统化的程序，遵守它是为了将开发和/或商业化 期间所获得的文件化知识和经验转移至恰当的负责的经过授权的另一方。

technology transfer report.

技术转移报告

A documented summary of a specific technology transferproject listing procedures, acceptance criteria, results achieved andconclusions.

一份列出了程序、可接受标准、得达成结果和结论的专用技术转移项目总结文件

validation.

验证

Action of proving and documenting that any process,procedure or method actually and consistently leads to the expected results.

证明和记录工艺、程序或方法可以实际并持续得到预期结果的活动

validation master plan (VMP).

验证主计划（VMP）

A high-level document that summarizes the manufacturer’soverall philosophy and approach, to be used for establishing performanceadequacy. It provides information on the manufacturer’s qualification andvalidation work programme and defines details of and timelines for the work tobe performed, including a statement of the responsibilities of thoseimplementing the plan.

汇总了生产商全面理念和方法，用于建立性能充分性的高层次文件。它提供 的是生产商的确认和验证工作程序，规定了准备执行的工作的时间表，包括 这些计划实施的职责说明。

validation protocol (VP).

验证方案（VP）

A document describing the activities to be performedduring validation, including the acceptance criteria.

一份描述在验证期间准备执行的活动包括可接受标准的文件

validation report (VR).

验证报告（VR）

A document in which the records, results and evaluationof validation are documented and summarized. It should also contain aconclusion of the outcome of the validation.

一份记录和汇总了验证记录、结果和评估的文件，还应包括有验证结果的结 论

4. Due diligenceand gap assessments

尽职调查和差距评估

4.1. A process of duediligence, gap assessment or audits of the SU and RU should be one of the firststeps when considering a technology transfer project.

在考虑技术转移项目时，首先应对转移方和接收方进行尽职调查、差距评估或审计。

4.2. The suitability and degree of preparedness of the RU should beassessed prior to the start of the transfer. The procedure to be followedshould be documented.

接收方的适当性和准备程度应在转移开始之前进行评估。应将应遵循的程序形成文件。

4.3. The assessment should be done by a team of appropriately qualifiedpersons with knowledge and experience in the field of GxP and the activity tobe transferred.

评估应由一个具有GxP领域知识和经验的适当资质的人员组成的团队来完成。

4.4. The assessment should further cover resources including personnel,premises, equipment and instruments, utilities, QC, documentation, computerizedsystems, qualification and validation and waste management.

评估应进一步涵盖资源，包括人员、厂房、设备和仪器、公用设施、质量控制、文件、计算机化系统、确认与验证以及废弃物管理。

4.5. The assessment to determine feasibility and readiness for technologytransfer may include technical, business, regulatory and legal aspects.

确定技术转移的可行性和准备情况的评估可能包括技术、商业、监管和法律方面。

5. Organization and management

组织和管理

5.1. All technology transfer activities should be organized andplanned.

所有技术转移活动均应得到组织和计划。

5.2. There should be a formal agreement between the parties whichspecifies the responsibilities of each party before, during and after transfer.The agreement should cover, for example, data management, data integrity,documentation and validation.

双方之间应有一份正式协议，具体规定双方在转移之前、期间和之后的责任。协议应包括，例如，数据管理，数据完整性，文件记录和验证。

5.3. All the necessary activities to be executed during thetechnology transfer project should be identified, organized and documented atthe start of the project. Responsibilities should be defined.

在技术转移项目开始时，应确定、组织和记录技术转让项目期间执行的所有必要活动。应该定义责任。

5.4. The SU should provide the necessary documentation relating tothe process, product or procedure to be transferred.

转移方应提供与所转移的工艺、产品或程序有关的必要文件。

5.5. The SU should provide criteria and information on inherentrisks, hazards and critical steps associated with the process, product orprocedure to be transferred. This may serve as a basis for the risk assessmentexercise.

转移方应提供与所转移的工艺、产品或程序相关的固有风险、危害和关键步骤的标准和信息。这可作为风险评估工作的基础。

5.6. The technology transfer should be managed by responsiblepersons from the SU and RU. A technology transfer team may be appointed withidentified and documented responsibilities.

技术转让应由转移方和接收方的负责人管理。可以任命一个技术转移小组，其职责应明确并形成文件。

5.7. The team members should have the necessary qualifications andexperience to manage the particular aspects of the transfer.

团队成员应该具备必要的资质和经验来管理转移的特定方面。

5.8. The SU should make all the necessary information and knowledgewith regard to the product, process or procedure available in relevantdocuments in order to ensure a successful transfer.

转移方应在相关文件中提供与产品、工艺或程序有关的所有必要信息和知识，以确保成功的转移。

5.9. A training programme should be implemented specific to theprocess, product or procedure to be transferred.

应针对待转移的工艺、产品或程序实施培训计划。

5.10. Any changes and adaptations made during the course of theproject should be fully documented and agreed to by both parties.

在项目过程中所作的任何变更和调整都应形成充分的文件，并经双方同意。

5.11. The execution of the technology transfer project should bedocumented in a report which is supported by the relevant data.

技术转移项目的执行情况应记录在一份报告中，并有相关数据支持。

5.12. Data should meet ALCOA+ principles.

数据应符合 ALCOA+原则。

6. Quality management and quality riskmanagement

质量管理和质量风险管理

6.1. The SU and RU should each have an appropriately designed,clearly defined and documented quality system.

转移方和接收方 都应该有一个适当设计、明确定义和书面的质量体系。

6.2. The quality system should be adequately resourced,implemented and maintained.

质量体系应有足够的资源，充分实施和维护。

6.3. The quality system should incorporate GxP which should beapplied to the life cycle stages of the products and processes, including thetechnology transfer.

质量体系应包含GxP，应应用于产品和工艺生命周期的各个阶段，包括技术转移。

6.4. The quality system should ensure that:

质量体系应确保：

6.5. Quality risk management should be implemented as a systematicprocess for the assessment, control, communication and review of risks.

质量风险管理的实施应包括对风险进行评估、控制、沟通和审核的系统过程。

6.6. The system for quality risk management should be described inwriting and cover appropriate areas such as, but not limited to, premises,equipment, materials, products, production, processes, QC, qualification,validation and the process of technology transfer.

质量风险管理体系应以书面形式描述，包括但不限于，厂房、设备、物料、产品、生产、工艺、QC、确认、验证和技术转移过程等适当领域。

6.7. The evaluation of the risk should be based on scientificknowledge and experience including that of the process and product.

风险评估应以科学知识和经验为基础，包括公司和产品的知识和经验。

6.8. The level of effort, formality and documentation of thequality risk management process should be commensurate with the level of risk.

质量风险管理过程的努力水平、正式程度和文件化程度应该与风险水平相适应。

6.9. The procedures and records for quality risk management shouldretained.

应保留质量风险管理的程序和记录。

7. Documentation

文件

Note: A list with examples ofdocuments commonly required in technology transfer is presented in Appendix 1.

注:附录1列有技术转移通常需要的文件示例。

7.1. An authorized technology transfer document should list theintended sequential phases and activities of the transfer. The document shouldinclude, for example, the following:

应有经批准的技术转移文件列出转移的预定阶段和活动。例如，该文件应包括下列内容:

7.2. Standard operating procedures (SOPs) should be followed,describing actions to be taken during the technology transfer process.

应遵循描述在技术转移过程中应采取行动的标准操作规程(SOPs)。

7.3. Records should be maintained for the activities performedduring the technology transfer process (e.g. a technology transfer report). Thereport content should reflect the protocol and SOPs that were followed. Thereport should summarize the scope of the transfer, the critical parameters asobtained in the SU and RU, and the final conclusions of the transfer. The discrepanciesand appropriate actions taken to resolve them should be recorded. Supportive documentswith data, results and other relevant information should be referenced in thereport and be readily available.

技术转移过程中进行的活动应保持记录(如技术转移报告)。报告内容应反映所遵循的方案和SOP。报告应总结转移的范围，在转移方和接收方中获得的关键参数，以及转移的最终结论。应记录偏差和为解决偏差而采取的适当措施。数据、结果和其他相关信息的支持性文件应在报告中引用，并随时可用。

8. Premises

厂房

8.1. The RU should haveappropriate premises with the layout, construction and finishing to suit the intendedoperations. Utilities such as heating, ventilation and air conditioning, aswell as gas and water systems, should be appropriate for the intended process,product or procedure to be transferred.

接收方应该有适当的布局、建筑和修整，以适应预期的操作。公用设施，如暖通空调，以及气体和水系统，应该适合待转移的工艺，产品或程序。

8.2. The SU should provide the RU with information on relevant health,safety and environmental issues, including:

转移方应向接收方提供有关健康、安全和环境问题的信息，包括:

9. Equipment and instruments

设备和仪器

9.1. The SU should provide a list of equipment and instrumentsinvolved in the production, filling, packing and QC testing. The list shouldinclude the makes and models of the relevant equipment and instruments.

转移方应提供一份生产、分装、包装和QC测试所涉及的设备和仪器清单。清单应包括相关设备和仪器的制造商和型号。

9.2. Other relevant documentation may include, on a case-by-casebasis as required, drawings; manuals; maintenance procedures and records;calibration procedures and records; as well as procedures such as equipmentset-up, operation and cleaning.

其他相关文件可能包括图纸(视具体情况而定);手册;维护程序和记录;校正程序和记录;以及设备设置、操作和清洗等的程序。

9.3. A review and a side-by-side comparison of equipment andinstruments of the SU and RU should be carried out in terms of their workingprinciple, make and models.

对转移方和接收方的设备和仪器进行工作原理、制造、型号等方面的审查和平行对比。

9.4. Where the review and comparison identify any gaps ordifferences, appropriate action should be taken. This may include theadaptation of existing equipment or acquisition of newequipment. Such action should be taken by following a changemanagement procedure which should be documented.

当审查和比较发现任何差距或差异时，应采取适当的措施。可能包括改造现有设备或购置新设备。这些措施应通过变更管理程序来进行，并应形成文件。

9.5. Production volumes and batch sizes at the SU and RU should becompared. Where batch sizes are different, the impact should be assessed andthe appropriate action planned and taken. Other factors relating to equipmentto be reviewed may include:

转移方和接收方的生产量和批量大小应进行比较。当批量大小不同时，应评估其影响，计划并采取适当的措施。与待审查设备有关的其他因素可能包括:

9.6. The impact of the potential product to be transferred, on existingproducts manufactured on site, should be assessed.

应评估待转移产品对现场生产的现有产品的影响。

10. Qualification and validation

确认与验证

10.1. The extent of qualification and validation to be performedshould be determined on the basis of risk management principles.

应根据风险管理原则确定确认和验证的范围。

10.2. The qualification of premises, utilities and equipmentshould be done in accordance with a qualification master plan and protocols.

厂房、公用设施和设备的确认应按照确认主计划和方案进行。

10.3. Validation, such as process validation, should be done inaccordance with a validation master plan and protocols.

验证，例如工艺验证，应该按照验证主计划和方案进行。

10.4. Where technology is transferred to commercial sites, thequalification of equipment and instruments should be completed prior to theactual technology transfer.

技术转移到商业化工厂的，应当在实际技术转移前完成设备、仪器的确认。

10.5. Process validation usually starts in research anddevelopment facilities either as prospective validation (traditional approach)or as stage I process validation (see references regarding the new approachesin process validation; and the life cycle approach). Note: Process validationshould be done according to current guidelines as published incurrent WHO Technical Report Series (3).

工艺验证通常从研发设施开始，或作为前瞻性验证(传统方法)，或作为第一阶段工艺验证(参见有关工艺验证新方法及生命周期方法的参考文献)。注:工艺验证应根据当前WHO技术报告系列(3)中发布的现行指南进行。

10.6. Procedures including processing and analytical procedures,should be appropriately validated at the SU and transferred to the RU followingdocumented procedures. Verification and validation, as appropriate, should becontinued at the RU as identified and documented in the technology transferprotocol.

程序，包括加工和分析程序，应在转移方进行适当的验证，并按照书面的程序移交给接收方。应在接收方继续进行确认和验证。

10.7. For cleaning procedures, development and validation shouldbe done in accordance with the guidelines as published in current WHO TechnicalReport Series (6). Points to consider when using HBEL in cleaning validation (14) should be taken into account in establishing cleaning procedures,cleanability studies and setting acceptance limits.

对于清洁程序，开发和验证应按照当前WHO技术报告系列(6)中发布的指南进行。在建立清洁程序、可清洁能力研究并设置可接受限度时，应考虑《在清洁验证中应用HBEL(14)的考量》。

10.8. Analytical procedures should be validated according to theguidelines as published in current WHO Technical Report Series (7).

分析程序应根据当前WHO技术报告系列(7)中发布的准则进行验证。

10.9. Qualification and validation procedures, protocols, data andresults should be appropriately recorded. The documents should be retained asdefined in procedures.

应适当地记录确认和验证程序、方案、数据和结果。文件应按照程序规定予以保存。

11. Product life cycle and project managementprinciples

产品生命周期和项目管理原则

11.1. The relevant stage of the life cycle of the facility,equipment, instrument, utility, product, process or procedure to be transferredshould be taken into consideration when the transfer is planned and executed.

在计划和实施转移时，应考虑转移的设施、设备、仪器、公用系统、产品、工艺或程序的生命周期的相关阶段。

12. Phases of a technology transfer project

技术转移项目阶段

12.1. The technology transfer project plan may be divided intodifferent phases. These may include, for example:

技术转移项目计划可以分为不同阶段。可能包括，例如：

Phase I: Project initiation

阶段1：项目启动

12.2. During the initiation phase of the project, a unit shouldnormally identify the need for the technology transfer. This may be because oflack of capacity, transfer from development to commercial site or transfer fromone company to another.

在项目的开始阶段，一个单位通常应查明技术转移的需求。这可能是由于缺乏能力、从开发现场转移到商业工厂或从一个公司转移到另一个公司。

12.3. The units should establish initial discussion and identifywhether or not there is any interest for such a project. (See also section ondue diligence above).

各单位应进行初步讨论，并确定是否有人对这一项目感兴趣。(另见上文尽职调查部分)。

12.4. The RU should be able to accommodate the intended activity.

接收方应能够适应预期的活动。

12.5. The RU should have the necessary technical expertise,technology and capability.

接收方应具备必要的技术知识、技术和能力。

12.6. A sufficient level and depth of detail to support theactivity, and any further development and optimization at the RU, should betransferred.

用以支持该活动的足够水平和深度的细节，以及任何需要在接收方进行的进一步开发和优化，也应进行转移。

Phase II: Project proposal

阶段2：项目计划

12.7. The SU and RU should jointly establish a team that will coordinateactivities and execute the technology transfer exercise.

转移方和接收方应该共同建立一个团队来协调活动并执行技术转移。

12.8. The team should perform a risk assessment based on theavailable data, information and knowledge of the premises, materials, products,procedures and other related information.

该团队应根据厂房、物料、产品、程序和其他相关信息的可用数据、信息和知识进行风险评估。

12.9. The team should prepare the technology transfer document.

该团队应准备技术转移文件。

12.10. The team should develop a control strategy which includes,for example:

团队应制定一个控制策略，其中包括，例如:

Phase III: Project transfer

阶段3：项目转移

12.11. The team should execute the project in accordance with theprocedures and agreed plan.

团队应按照程序和商定的计划执行项目。

Production: Starting materials

生产:起始物料

12.12. The specifications and relevant functional characteristicsof the starting materials (APIs and excipients) to be used at the RU should beconsistent with those materials used at the SU. Any properties which are likelyto influence the process or product should be identified and/or characterized.

Active pharmaceutical ingredients

活性药物成分

12.13. The SU should provide the RU with the open part of the DrugMaster File (API master file), or equivalent information, as well as anyrelevant additional information on the API of importance for the manufacture ofthe pharmaceutical product. The following are examples of the information whichmay typically be provided; however the information needed in each specific caseshould be assessed using the principles of QRM:

转移方应向接收方提供药物主文件(API主文件)的开放部分，或同等信息，以及对药品生产具有重要意义的API的任何相关额外信息。以下是通常情况下提供的资料的例子;然而，每个具体情况所需的信息应使用QRM原则进行评估:

Excipients

辅料

12.14. The specifications and relevant functional characteristicsof excipients should be made available by the SU for transfer to the RU site.The following are examples of the information which may typically be provided;however, the information needed in each specific case should be assessed usingthe principles of QRM:

转移方应提供辅料的标准和相关功能特性，以转移到接收方。以下是通常情况下提供的资料示例;然而，每个具体情况所需的信息应使用QRM原则进行评估:

Information on process and finishedpharmaceutical product information

工艺信息和成品信息

Processing, packaging

工艺、包装

12.15. Product, process and procedure knowledge should be anessential part of the transfer process from SU to RU.

产品、工艺和方法知识应该是从 SU 转移至RU 的重要部分。

12.16. The quality target product profile, critical qualityattributes, critical process parameters, material attributes, control strategyand any other impacting elements on the quality of the product should beavailable. (See also ICH guidelines.)

质量目标产品概况、关键质量属性、关键工艺参数、原料属性、控制策略和所有其它影响产品质量的要素均应可提供（亦参见 ICH指南）。

12.17. The SU should provide the total product quality profilewith its qualitative and quantitative composition, physical deion, methodof manufacture, in-process controls, control method and specifications,packaging components and configurations, and any safety and handling considerationsto the RU. SU 应提交所有的产品质量概况及产品成分名称和各成分比例、物理状态、生产方法、中控、控制方法和标准、包装材料和参数，以及 RU的所有安全和处置考量。

12.18. The SU should provide any information on the history ofprocess development which may be required to enable the RU to perform anyfurther development and or process optimization after successful transfer.

SU 应提交工艺开发的所有历史信息，这些信息可让 RU 在转移成功之后进行更深入的开发工作或工艺优化。

12.19. Such information may include the following:

此类信息可包括以下内容：

12.20. The SU should provide to the RU information on any health,safety and environmental issues associated with the manufacturing processes tobe transferred, and the implications thereof (e.g. need for gowning or protectiveclothing).

SU 应向 RU 提供与转让的生产过程相关的任何健康、安全和环境问题的信息，以及由此产生的影响(例如，是否需要服装或防护服)。

12.21. The SU should provide to the RU information on currentprocessing and testing, including but not limited to:

SU 应向 RU 提交当前工艺和检测方面的资料，包括但不仅限于：

12.22. During the transfer process, the RU should identify anydifferences in facilities, systems and capabilities and discuss these with theSU. The potential impact should be understood and satisfactorily addressed inorder to assure equivalent product quality. Based on the information receivedfrom the SU, the RU should consider its own capability to manufacture and packthe product to the required standards and should develop the relevant siteoperating procedures and documentation before the start of routine production.

12.23. Process development at the RU should address the followingtasks:

RU 的工艺开发应完成以下任务：

Packaging

包装

12.24. The transfer of packaging operations should follow the sameprocedural principles as those of the product processing.

包装操作的转移应遵循与产品工艺相同的程序原则。

12.25. Information on packaging to be transferred from the SU tothe RU should include specifications for a suitable container and closuresystem, as well as any relevant additional information on design, packing, processingor labelling requirements and tamper-evident and anti- counterfeiting measures.

从 SU 转移到 RU的包装信息应包括合适容器和封闭系统的规格，以及设计、包装、加工或标签要求、防拆封和防伪措施等相关附加信息。

12.26. For QC testing of packaging components, specificationsshould be provided including drawings, artwork and material.

对于包装部件的质量控制测试，应提供包括图纸、图纸和材料在内的标准。

12.27. Based on the information provided, the RU should perform asuitability study for the initial qualification of the packaging components.

根据所提供的信息， RU 应该对包装部件的初始确认进行适用性研究。

12.28. Packaging is considered suitable if it provides adequateprotection (preventing degradation of the medicine due to environmentalinfluences), safety (absence of undesirable substances released into theproduct), compatibility (absence of interaction possibly affecting medicine quality)and performance (functionality in terms of drug delivery).

如果包装能提供足够的保护（防止药物因环境影响而降解） 、安全性(不产生不良物质进入产品)、相容性（不产生可能影响药物质量的相互作用)和性能(药物传递的功能性)，即认为包装是合适的。

Quality control: analytical method transfer

质量控制：分析方法转移

12.29. Analytical methods used to test pharmaceutical products,starting materials, packaging components and cleaning (residue) samples, ifapplicable, should be implemented at the testing laboratory before the testingof samples for process validation studies is performed by the RU.

在 RU 开始对工艺验证研究样品进行检测之前，应在检测实验室执行检测药品、起始物料、包装材料和清洁（残留）样品（如适用）所用的分析方法；

12.30. A protocol defining the steps should be prepared fortransfer of analytical methods. The analytical methods transfer protocol shouldinclude:

应起草方案规定分析方法转移的步骤。分析方法转移方案应包括：

12.31. The SU’s responsibilities for the transfer of analyticalprocedures are to:

SU 在分析方法转移过程中的职责：

12.32. The RU should exercise its responsibility to:

RU 应履行其义务：

12.33. The appropriate training should be provided and alltraining activities and outcomes should be documented.

应提供适当的培训，并记录培训活动和培训结果。

12.34. Reference should be made to compendial monographs such asThe International Pharmacopoeia, European Pharmacopoeia, British Pharmacopoeiaand United States Pharmacopeia), where these are available.

应参考药典各论（如有）如国际药典、欧洲药典、英国药典、美国药典。

12.35. An experimental design should be prepared which includesacceptance criteria for the main analytical testing procedures. (See Appendix2.)

应对实验进行设计，其中包括主要分析方法的可接受标准（参见附录 2）。

12.36. Where products are transferred from one unit to another,the applicable analytical procedures should also be transferred.

如果产品是从一个部门转移至另一个部门，亦应转移相关的分析方法。

12.37. All relevant analytical procedure development andvalidation documentation should be made available by the SU to the RU.

SU 应向 RU 提供所有相关的分析方法开发和验证文件。

12.38. The appropriate transfer protocols and procedures should befollowed when analytical procedures are transferred.

在分析方法转移过程中应遵守适当的转移方案和程序。

12.39. The number of analysts involved in the transfer, from bothSU and RU, should be defined and justified.

从 SU 转移至 RU过程中所涉及的化验员的数量应予以规定和论证。

12.40. The parameters of the analytical procedure to be includedin the validation should be defined and justified.

应规定验证中需包括的分析方法的参数并说明原因。

12.41. Acceptance criteria should be set to determine the successof the transfer. Statistical trending of results should be considered in orderto show capability of the procedure.

应设定可接受标准，从而确定转移是否成功。应考虑结果的统计学趋势，以显示工艺能力。

Cleaning

清洁

12.42. To minimize the risk of contamination and cross-contamination,adequate cleaning procedures should be followed.

为尽可能降低污染和交叉污染的风险，应严格遵守清洁程序。

12.43. Cleaning procedures and their validation should normally besite-specific. In order for the RU to define its cleaning strategy, the SUshould provide information on cleaning at the SU to minimize cross-contaminationdue to residues from previous manufacturing steps, operator exposure andenvironmental impact, including:

清洁程序及其验证通常为场所专用。为了让 RU 制订其清洁策略，SU 应暖手袋在 SU 的清洁信息，以尽可能减少由于之前生产步骤残留、操作工暴露和环境影响带来的交叉污染，其中包括：

12.44. Additional applicable information should be provided, suchas:

应提供其它相关信息如：

12.45. Before the transfer, the SU should provide information onlimits for product residues and the rationale for limit selection.

在转移之前， SU 应该提供关于产品残留限量和限量选择的基本原理的信息。

12.46. Based on the information provided by the SU, cleaningprocedures should be designed at the RU, taking into account relevantcharacteristics of the starting materials (e.g. potency, toxicity, solubility,corrosiveness and temperature sensitivity), manufacturing equipment design andconfiguration, cleaning agent and product residue.

根据 SU 提供的信息，应在 RU处设计清洗程序，考虑起始物料的相关特性(例如，效力、毒性、溶解度、腐蚀性和温度敏感性)、制造设备的设计和配置、清洗剂和产品残留物。

Phase IV: Project review

第四阶段：项目审核

12.47. The progress and success of the transfer of technologyshould be monitored and reviewed during and after completion of the project.

在项目完成期间和之后，应监测和审核技术转让的进展和是否成功。

12.48. Compliance with the procedures and protocols should beverified. Deviations and changes should be documented and investigated whereappropriate.

应核查对程序和规程的遵守情况。偏差和变更应记录在案， 适当时应进行调查。

12.49. Where possible, data and results should be subjected toappropriate statistical calculation and evaluation to determine trends,compliance with control limits and capability studies.

在可能的情况下，应对数据和结果进行适当的统计计算和评价，以确定趋势、 与控制限度的符合情况和能力研究。

12.50. A technology transfer report should be prepared, based onthe data and information obtained during the project. The supportive datashould be kept and be accessible.

应根据项目期间获得的数据和资料编写一份技术转让报告。支持性数据应保存并便于查阅。

12.51. The report, which should include a conclusion, should beauthorized by the persons responsible to do so.

该报告应有结论并由相应人员批准。

Appendix 1 Example of documentation commonlyrequired for the transfer of technology

附录1技术转移通常需要的文件示例

* Thetable below provides an example of documentation commonly required for thetransfer of technology.

下表提供了技术转移通常需要的文件示例。

*Note: These are examples. All therequired documents should be identified for the different tasks.

Appendix 2 Exampleof possible experimental designs and acceptance criteria for analytical testing

附录2. 分析测试可能的实验设计和接受标准示例

The table below provides an example of possible experimental designs andacceptance criteria for analytical testing. The numbers in the table are givenas examples only and should not be considered as recommendations. Methodtransfers should account for the variability and sensitivity of the method andthe specifications for the quality parameter. Alternative procedures andacceptance criteria may be applied based on science and the characteristics ofthe analytical method and the analyte.

下表提供了分析测试可能的实验设计和接受标准的示例。表内的数字只是举例，不应视为建议。方法转移应该考虑方法的可变性和灵敏度以及质量参数的标准。基于科学和分析方法、被分析物的特点，可以采用其他的程序和接受标准。

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