-
精品
WHO
第
961
号技术报告
附件
7
药物生产技术
转移指南（中英文
1/4
）
2013-09-29 14:16:27|
分类：
WHO
|
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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
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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.
< br>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
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between
manu
facture 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关其文
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。
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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、
和平和质量控制各方面。
一般会有一个
转出
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方
(S
U)
，
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
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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。
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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
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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）
，
< br>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。
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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<
/p>
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<
/p>
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.
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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。
W
HO
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.
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—
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,
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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。<
/p>
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。
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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。
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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。
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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
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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
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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.)
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证明设备或系统能持续运行，<
/p>
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.
< br>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
）。
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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)
.
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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
）。<
/p>
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。
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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.
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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 overall
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.
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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.
< br>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。
< br>
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.
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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<
/p>
可进入下一步骤
—
identification of critical control
points;
关键控制点的识别
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—
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，<
/p>
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
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transferred,
to serve as a basis for a quality risk management
(QRM)
exercise at the RU (
7<
/p>
–
10
).
<
/p>
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
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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。
< br>
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
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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.
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要考虑能支持接收方的生产、<
/p>
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.
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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<
/p>
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
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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;
溶解性概况
if relevant, pH in solution;
必要时，溶液的
pH
值
partition coefficient, including
the method of determination;
分配比例，包括所用的检测方法
intrinsic dissolution rate, including
the method of determination;
特性溶出速率，包括所用的检测方法
particle size and distribution,
including the method of
determination;
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粒径分布，包括所用的检测方法
bulk physical properties, including
data on bulk and tap density,
surface area and porosity as
appropriate;
散装物理特性，包括松密度和紧密度，表面积和孔隙度（适用时）
water content and determination of
hygroscopicity, including water
activity data and special handling
requirements;
水份，吸湿性测试，包括水活性数据和特殊的处置要求
microbiological considerations
(including sterility, bacterial
endotoxins and bioburden levels where
the API supports
microbiological
growth) in accordance with national, regional or
international pharmacopoeial
requirements;
微生物（包括无菌性、细菌内毒素，如果辅料支持微生物生长的话，还包
括
生物负载水平）符合国家、地区或国际药典要求
specifications and justification for
release and end-of-life limits;
放行标准和论证，生命终结期时的限度
summary of stability studies conducted
in conformity with current
guidelines, including conclusions and
recommendations on retest
date;
根据现行指南已进行的稳定性研究的总结，包括复验期的结论和建议
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list of potential and observed
synthetic impurities, with data to
support proposed specifications and
typically observed levels;
潜在的和已观察到的合成杂质清单，满足所提议的质量标准的数据和代表
性观察水平
information on degradants, with a list
of potential and observed
degradation
products and data to support proposed
specifications
and typically observed
levels;
降解物信息，潜在的和已观察到的降解产物和满足所提议的限度的数据及
典型水平
potency
factor, indicating observed purity and
justification for any
recommended
adjustment to the input quantity of API for
product
manufacturing, providing
example calculations; and
效价因子，包括观察到的纯度，生产过程中原料药加入调整量的推荐值的
论述，举例说明计算方式，以及
special considerations with
implications for storage and or
handling, including but not limited to
safety and environmental
factors (e.g.
as specified in material safety data sheets) and
sensitivity
to heat, light or
moisture.
关于存贮和处置的特殊考虑内容，包括但不限于安全和环境因素（例如，
在
MSDS
中说明）和对热、光、湿的敏感性
Excipients
辅料
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5.7 The
excipients (
11
) to be used
have a potential impact on the final
product. Their specifications and
relevant functional characteristics
should, therefore, 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 using the principles of
QRM:
用于生产的辅料（
11
）如果对成品有潜在影响，其质量标准和相关的功能性特
性应由转出
方转移给接收方。
以下为代表性信息样例，
特殊情况下所需要的
信息
应采用风险管理方法原则进行评估
manufacturer and
associated supply chain;
生产商和相关的供应链
description of functionality, with
justification for inclusion of any
antioxidant,
preservative or any excipient;
如有添加抗氧剂、防腐剂或辅料，应有其功能描述及论证
definitive form (particularly for solid
and inhaled dosage forms);
最终的剂型（尤其是固体和吸入剂型）
solubility profile (particularly for
inhaled and transdermal dosage
forms);
溶解性概况（尤其是对吸入和透皮剂型）
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partition coefficient, including the
method of determination (for
transdermal dosage forms);
分配比例，包括所用的测试方法（透皮剂型）
intrinsic dissolution rate, including
the method of determination
(for transdermal dosage
forms);
特性溶出速率，包括所用的检测方法（透皮剂型）
particle size and distribution,
including the method of
determination (for solid, inhaled and
transdermal dosage forms);
粒径分布，包括所用的测试方法（固体、吸入剂和透皮剂型）
bulk physical properties, including
data on bulk and tap density,
surface area and porosity as
appropriate (for solid and inhaled
dosage forms);
散装物理特性，包括松密度和紧密度，适当时还包括表面积和孔隙度（固
体和吸入剂型）
compaction properties (for solid dosage
forms);
压制特性（固体剂型）
melting point range (for semi-solid or
topical dosage forms);
熔点范围（半固体或局部用药）
pH
range (for parenteral, semi-solid or topical,
liquid and
transdermal dosage
forms);
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pH
范围（注射剂、半固体剂、局部用药、液体和透皮剂型）
ionic strength (for parenteral
dosage forms);
离子化强度（注射剂型）
specific density or gravity (for
parenteral, semi-solid or topical,
liquid and transdermal dosage
forms);
密度或比重（注射剂、半固体或局部用药、液体和透皮剂型）
viscosity and or viscoelasticity (for
parenteral, semi-solid or topical,
liquid and transdermal dosage
forms);
粘性和粒弹性（注射剂、半固体剂或局部用药、液体、透皮剂型）
osmolarity (for parenteral dosage
forms);
摩尔浓度（注射剂型）
water
content and determination of hygroscopicity,
including water
activity data and
special handling requirements (for solid and
inhaled
dosage forms);
水分和吸湿性测试，包括水的活性数据和特
殊的处置要求（固体和吸入剂
型）
moisture content range (for parenteral,
semisolid or topical, liquid
and
transdermal dosage forms);
水分控制范围（注射剂、固体或局部用药、液体和透皮吸收剂型）
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microbiological considerations
(including sterility, bacterial
endotoxins and bioburden levels where
the excipient supports
microbiological
growth) in accordance with national, regional or
international pharmacopoeial
requirements, as applicable (for
general and specific
monographs);
微生物特性（包括无菌性、细菌内毒素，如果辅料支持微生物生长的话，
还包
括生物负载水平）应符合国家的、地区的或国际药典要求，适用时（通
论和各论）
specifications and justification for
release and end-of-life limits;
放行和生命终结时间点质量标准和论述
information on adhesives supporting
compliance with peel, sheer
and adhesion design criteria (for
transdermal dosage forms);
贴剂符合剥离性、透明和粘性设计要求的信息（经皮给药剂型）
special considerations with
implications for storage and or
handling, including but not limited to
safety and environmental
factors (e.g.
as specified in material safety data sheets
(MSDS)) and
sensitivity to heat, light
or moisture; and
关于存贮和处置时的特殊考虑，包括但不仅限于安全和环境因素（例如，
MSDS
），和热敏性、光敏性、吸湿性，以及
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