-
无源医疗器械技术文件和设计文档指南
Whereas the term “
Technical
File
“ is used for Medical Devices of
class I, class IIa
and class
IIb, the term “
Design
Dossier
“ is used for the class III
products.
标题中的“技术文件”适用于
I
类，
IIa
类
,IIb
类医疗器械，“设计文档”适用于
II
I
类医疗
器械。
Technical Files are retained in the
premises of the manufacturer or the Authorized
Representative for potential review of
Competent Authorities and Notified Body.
Part B of the Technical File may be
available at the manufacturer only.
技术文
件是保留在制造商或授权代表单位的主管部门和认证机构。部分技术文件
B
部分
只保留在制造商处。
Whereas Design Dossiers have to be
submitted to the Notified Body for review prior to
CE-Marking
of
the
product
(use
form
Application
for
CE
Conformity
Assessment
(Product)MED_F_03.03). We
will
assign
a
project
manager
who
will
entrust
one
or
more
further
experts
with
the
review
of
particular
modules.
All
experts
are
at
your
disposal
directly
or
indirectly
through
the
project
manager.
After
successful
review,
the Notified Body issues a design
examination certificate according to Annex II.4 of
the Council Directive certifying
compliance with the relevant provisions of Annex I
of
the MDD.
设计档案材料已被提交到公告机构用
于需要
CE
认证前的产品审查（用
CE
合格评定（产
品）
MED_F_03.
03
规定的格式）。我们将委派一个项目经理，他将委托一个或多个资
< br>深专家审查特定的模块。
所有专家会直接或通过项目经理间接与你接触，在成功的
审查
后，公告机构会按照
MDD
法规附
件
I
和附件
II.4
< br>相关规定签发检验证书。
Article 5 of
the Council Directive describes consideration of
the European harmonized
standards by
the manufacturer in order to demonstrate
compliance with the Essential
aspect
is
even
more
important
as
International
Standard
Organizations
have
adopted
European
Norms
(and
vice
versa)
and
demonstrating
compliance
with
these
standards
could
be
very
helpful
in
international
mutual
recognition of the
CE-Marking process.
理事会指令
5
描述了制造商要遵守的欧洲统一标准，以证明附合基本要求，这方面更重
要的是为国际标准组织已经通过了欧洲规范（反之亦然），并且遵守这些标准可能非常
有助于国际的相互承认在
CE
认证过程中。
< br>
It is not necessary to include all
documents in the Design Dossier which have already
been
subject
to
an
ISO
/
EN
/
MDD
Audit
by
the
Notified
Body.
Examples
of
documents not necessary to be included
are Quality Manuals and related lower level
documents.
设计档案材料不必一定包括那些已经提交给
ISO
/
EN
/
MDD
审查公告机构的所有的文
档，例如文档不必包括质量手
册和一些相关更下层文档。
If the
manufacturer of a class III device provides
detailed information according to the
checklist
described
below,
the
requirements
of
the
Directive
are
appropriately
addressed.
如果一个类
III
器件制造商提供详细的资料
按下述清单，该指令的要求得到适当处理
This is
even more important in case a Competent Authority
or another Notified Body
wishes to
review the documentation.
这样很重要如果主管部门或其他认证机构要审查文件
Generally,
the
information
should
be
provided
as
conclusions,
summaries,
reports,
tables
or
flow
charts
(with
reference
to
the
full
documentation
in
the
Essential
Requirement checklist).
一般的，
提供的信息应包括结论，摘要，报告，表或流程图（参照完整文档在基本要求
检查表中）
Special
care
should
be
taken
to
ensure
that
any
information
is
consistent
throughout
the
Design
Dossier
(e.g.
description
and
variants
of
the
device
in
different
documents;
adverse
events
as
stated
in
the
IFU
and
hazards
in
normal
condition as well as in fault condition
in the Risk Management).
特别应注意确保任何信息在整个
卷中是一致的
（例如：
在不同的文档中器械的规格描述；
说明书中不良事件的声明和在正常情况下的危害，以及在故障情况下的风险管理）
A complete pagination of the
Design Dossier or another type of control
mechanism is
necessary, e.g. revision
control of each section. Two copies of the
documentation and
an electronic
version, if possible are required to achieve an
appropriate review time.
设计档案材料必须有完整的页码
控制或者另外形式的控制机制，
例如，
每个章节的版本控制。<
/p>
两
份拷贝和一个电子版本，如果可能还需要一个审查时间。
In general, design changes
described in the MDD (93/42/EEC), Annex II.4.4
shall be
reported to the Notified Body
(use form Change Notification MED_F_09.04) in
order to
ensure conformity with the
requirements defined in the Annex II.4.4 and in
order to
ensure that the
Design Dossiers retained at the
Notified Body?s archive are complete
and up-to-date
.
一般来说，
设计更改在
MDD
(93/42/EEC),
附肵
II.4.4
有说明，
应向公告机构报告确保更
改合适（按
MED_F_09.04
更改通知书格式）。
Furthermore at least one
sample of the device
should
be provided.
此外，至少应提供一个设备样品
For
all data SI units of
measurement
shall be used.
对
于所有
SI
单位的测量数据应得到使用。
Important hint: Design Dossiers that
accurately conform to the below guidance
can be reviewed more efficiently!
重要提示：设计档案材料准确地符合以下指导可以更有效地进行审查
In
this
regard
it
is
recommended
to
compile
a
Design
Dossier
or
Technical
File
as
follows
在这方面，建议编制设计档案材料或技术文件如下
(
也可看
NB-MED/2.5.1
和
GHTF
文档
SG1
(PD)/N011R20: STED):
PART A: Technical File
A
部分
技术文件
1. Table of
Content
目录
2.
Introduction
介绍
3.
Design Dossier/Technical File Summary Information<
/p>
设计档案材料
/
技术文件摘要信
息
PART B:
Annexes
B
部分
附件
1. Essential
Requirements
Checklist
基本要求检查表
2. Risk
Analysis
风险分析
3.
Drawings, Design -, Product -
Specifications
图纸，设计
-
产品
-
规格
4. Chemical,
Physical and Biological
Tests
化学，物理和生物测试
4.1 In Vitro Testing - Preclinical
Studies
体外试验
-
临床前研究
4.2 In Vivo
Testing - Preclinical
Studies
体内试验
-
临床前研究
4.3
Biocompatibility
Tests
生物相容性测试
4.4
Bio-stability Tests
生物稳定性试验
4.5 Microbiological Safety, Animal
Origin Tissue
微生物安全，动物保护组织
4.6 Drug / medical device combination
药物
/
医疗设备组合
4.7 Blood Derivates, Human Tissue /
medical device combination
血液衍生物，人
体组织
/
医疗设备组合
4.8 Coated Medical
Devices
涂层医疗器械
5.
Clinical Data
临床资料
6. Labels and Instructions for
Use
标签和使用说明
7.
Manufacturing
制造
8. Package Qualification and Shelf
life
包装和保质期
9.
Sterilization
灭菌
10. Conclusion
结论
11. Declaration of Conformity
(Draft)
符合性声明（草稿）
PART A: Technical
File
A
部分
技术文件
1. Table of
Content
目录
Content of both Parts A and B
目录包括
A
部分和
B
部分
2. Introduction
介绍
??
Revision
history
of
Design
Dossier:
change
notifications,
revision
numbers
and
approvals of all documents including
all amendments.
设计文档案修订历史：更改通知，版本号和
批准的所有文件，包括所有的修订
??
Regulatory
Information
法规信息
o
Name, postal address,
Notified Body, certifications (valid copies
attached!) of:
以下机构的名称，通讯地址，公告机构，证书（有效的
复的复印件）
??
the
manufacturer (incl. contact
person)
制造商（包括联系人）
??
OEM, critical suppliers,
subcontractors (e.g. contract sterilizer) OEM
，关键供应
商，外协商（例如：合同灭菌商）
??
European Representative
(if applicable)
欧盟代表（如果适用）
o
Product
and
accessory
classification,
rule
according
to
MDD,
Annex
IX
and
according to ISO 10993-1
Table 1 and 2
产品及配件分类：按照
MDD<
/p>
规定的附录
9
和
ISO10993-1
表
1
和表
2
o
Conformity
Assessment Route
合格评定路径
Annex II.3+II.4
o
UMDNS-/GMDS-code UMDNS-/GMDS
编号
o
Product History: approvals (e.g. FDA
510(k) or PMA clearance), market release,
status of any pending request for
market clearance; items sold
上市销售历史，证书，
时间，数量
??
Brief description of the
product
产品简要描述
o
Intended use, model names,
configurations, variants
产品预期用途，
< br>型号规格名称，
配置和规格表
o
Accessories for the
product, integral parts of package
产品的附件
,
同一包装的部件
o
Applied standards (list or
table including the full title, identifying
numbers, date, and
the organization
that created the standard)
适用标准（全名的列标，包括
编号，日期
和该标准的编制机构）特别协调标准
Note: Please make sure to use current
standards only or provide a gap analysis
and rationale
注：
请务
必使用唯一最新标准或提供差距分析和理由
o
Rationale if applicable standards or
parts thereof have not been considered
如为何没有采用当前标准或部分标准的理由
3. Design Dossier / Technical File
Summary Information (reference to
supporting documents filed in Part B) <
/p>
设计档案材料
/
技术文件摘要信息（参照
B
部分支持文档）
??
Comprehensive
description
of
the
system
and
each
functional
component
of
the
device
and
the
related
accessories
including
utilized
material
or
ingredient
(animal/human
origin, drug device combination?), packaging,
method of sterilization,
shelf
life,
combination
with
active
medical
devices.
The
description
should
be
supported by diagrams, photographs or
drawings, as appropriate.
综合描述：整个系统的（包括
包装），产品的每个功能部件和相关的附件包括关键材料
或组成部分
（动物
/
人类
,
< br>
药物组合装置
）
,
包装
,
灭菌方法
,
有效期
,
配合使用的有源医疗器械
,
描述应有适用的简图
,
照片或工程图
.
??
Basic scientific concepts
that form the fundamentals for the device
including medical,
biological,
chemical, and physical background information
产品依据的基本的科学概念
,
包括材料
,
生物
,
化学和物理背
景资料
.
??
In case of
a Change Notification: description of all changes
in comparison with the
previous design
or manufacturing process (e.g. tabular format)
更改通知
:
所有的变化描述与先前的设计或制造过程中的比较
(
例如
:
列表的格式
)
??
Summary of the essential
data and results as detailed in Part B
B
部分中关键数据和结果摘要
??
Information as provided in
the Instructions / Directions for Use (detailed in
section B):
Intended
Use,
Indication,
Contraindications,
Warnings,
Adverse
events,
Operation
and use of
accessories
使用说明提供的信息
:
使用指导
(
详细见
B
部分
),
用途
,
标志
,
禁忌
,
警告
,
不良反应
,
操作和使
用的配件
??
Planned
changes
计划中的改变（规格型号）
??
Summary description of
manufacturing
process
简要介绍制造过程
??
Any other important
safety/performance related information.
任何其他重要的安全特性
:
性
能相关的信息
This structure
enables efficient project planning and management.
Part A can be used
for a pre-review in
order to instantly notify the manufacturer of open
issues or in case
particular aspects
are not covered in the Design Dossier.
这种结构应该能够有效的项目规划和管理。
< br>A
部分可用于预先审查，以便即时通知制造商显尔易见的问题
或某些具体方面没有包括在设计开发资料中的问题
PART B: Annexes
B
部分
附件
1. Essential Requirements
Checklist
基本要求检查表
Example:
例
:
E.R.
applicability
standards (with
compliance
基本要求
all applied
date of issue)
demonstrated
by
是否适用
标准
(
带有效发布时
(referenced
间
)
documents)
证明材料
(
参考文档
)
7.1
Yes
ENISO10993-1:2003
laboratory
test reports:
(text)
是
/
否
-5:1999
-
cytotoxicity
(report
内容
等
number and date)
EN62336=IEC62336
实验室测试报告
-
细胞毒性
(
报告
编号和日期
)
location
–
section
所在章节
Section
a)
b) c)
6.1
节
See
also
Attachment
I:
European
Norms
and
Standards
and
other
Documents
supporting Technical Files and Design
Dossiers.
另见附件
I:
欧洲的规范和标准及配套技术文件和其他设计档案材料
2. Risk
Analysis
风险分析
The
document
(Risk
Management
File)
which
describes
the
result
of
the
risk
management (including risk analysis,
evaluation, mitigation and overall residual risk
evaluation and production/post
production information see ISO 14971 fig. B1 for
an
overview) process should contain at
least the following information:
风险管理文档
描述了风险管理的结果
(
包括风险分析
,
风险评估
,
风险降低和剩余风险评<
/p>
价以及按照
ISO 14971 fig. B1
进行的生产
/
生产后信息评价
),
风险分析程序到少包括下面
和信息
;
??
General
information
简要信息
o
Summary
概要
o
Purpose of the document
including project phase(s) / life cycle phase(s)
for which
the
risk
analysis
was
performed
and
reviewed
Scope
(e.g.
design/product,
manufacturing
process,
user/operation);
product
identification
and
description;
intended use,
shelf life.
文件的目的包括项目阶段（第）
/<
/p>
风险分析进行的生命周期阶段（
s
）和审
查范围
(
例
:
设计／生产制造程序，
使用者／操作
)
；产品标识和说明，用途，有效期。
o
Reference
to:
Risk
Management
SOP
and
Plan,
Risk
Management
Policy,
standards
(EN
ISO
14971,
ISO
22442
part
1
-3
and
MEDDEV
2.5-8
strongly
recommended),
specification documents, design documents,
procedures, protocols,
reports,
manufacturing and production process information <
/p>
参考：
风险管理标准操作程序和计划，
风
险管理政策，
标准
（
EN ISO
14971, ISO 22442
第
1 -3
和
MEDDEV 2.5-8
强制执行），
规范文件，设计文档，规程，协议，报告，制造和生产过
程的信息
o
Definition
of terms, abbreviations and acronyms
术语定义，缩略语
o
Participants
of
the
risk
analysis
team
(persons
and
organisations),
their
qualification,responsibility and
authority.
风险分析团队（个人和组织），他们的证书，职责和权力。
o
Note: the Risk Analysis
shall include a medical knowledgeable and
experienced
expert in the corresponding
field of application.
注：风险分析应有一个具有医疗知识和相关领域应用经验的专家
o
Note: The Risk Management
Plan according to ISO 14971 -especially in
relation to
risk
acceptance
criteria-
has
to
be
defined
by
the
top
management
under
consideration
of
the
estimated
production
volume
to
be
sold
per
year
and
under
consideration of
regulatory requirements.
注：
风险管理计划根据
ISO 149
71
－尤其是有关风险接受准则－已被高层管理人员定义（考虑预计每年的
产量和销售量以及监管规定）
o
Identification
of
medical
device
characteristics
that
could
impact
on
safety,
e.g.
according to ISO 14971.
识别可能影响安全的医疗设备的特征，例：参照
ISO
14971
o
If
applicable consideration of data obtained from
literature review, usability testing,
market surveillance of similar devices,
post market surveillance or post market
clinical follow-up (also related to
e.g. change notifications, predicate or otherwise
comparable devices): complaint history,
incidents per number of devices sold,
analysis of underlying causes and final
outcome, corrective and preventive action
including proof of effectiveness
如果适用性审议的数据来自文献回顾，
可用性测试，
市场类似产品对比，
产品售后信息和售后临床随访
（其
他相关的如：更改通知，其他方式类似装置
）
投
诉历史，事故占销售设备的数量，分析事故原因及最终结
果，纠正和预防措施，包括有效
的证明。
o
Revision
history
修订历史
??
Methodology
评估方法
o
Hazards / hazardous
situations in normal condition
: Hazard
Analysis; patient/
user related (top-
down approach), e.g. Fault Tree Analysis, table
format
在正常状态下的危害
/
危害性情况
;
危害分析
;
病人
/
相关使用者
(
自上而下方法
),
例如
:
失效
的树形分析
,
表格格式
??
Clinical experience and
clinical risks
临床经验和临床风险
??
Method for identification
of applicable hazards; sources of information used
识别可适用性危害的方法
;
所用信息的
来源
??
Method
for
determination
of
the
potential
causes
of
hazards;
sources
of
information used
< br>判定危害的潜在原因的方法
;
所用信息的来源
??
System used for
categorization of severity levels (e.g. examples);
description
of consequences to
patients, users and other persons
严重程度的
分类系统
(
例如
:
举例
);
对病人
,
用户和其它人产生的后果描述
??
System used for
categorization of occurrence of each hazard cause
(probability
estimate, frequency
expressed as e.g. ?events per device and
time?)
每种危害原因产生的分类系统
< br>(
可能性估计
,
频率表述为
”
根据器械和次数的事件
”
)
??
Method for
combination of severity and occurrence to risk
level (e.g. diagram,
graph, formula)
风险水平的严重和发生的组合方法
(
例如<
/p>
:
图表
,
图形<
/p>
,
公式
)
??
Criteria for risk
acceptance (e.g. acceptable, ALARP, unacceptable)
under
consideration of the risk
management plan and accumulated risks
考
虑到风险管理计划和累计风险情况下的风险可接受性标准
(
例如
:
可接受
,
可操作又合
理的最低情况
,
不可接受
)
??
Note: If residual risks
remain in ALARP region a rational should be ready
to
substantiate that no further
mitigation was possible according to risk control
option analysis.
注意
:
如果剩余风险是在
”
可操作又合
理的最低情况
”
的范围内
,
应该根据风险控制选择分
析合理地证实没有其它的缓解措施
.
o
Hazards / hazardous
situations in fault condition
: e.g.
FMEA; device related
(bottom-up
approach)
在失效状况下的危害
/
< br>危害性情况
:
例如
:
潜在失效模式及后果分析
;
相关器械
(
自下而上
方法
)
??
Method for
identification of applicable failure modes;
sources of information
Used
适用的失效模式识别方法
;
所用信息来源
??
Method for determination
of the potential causes of failure modes; sources
of
information used
失效模式的潜在原
因的判定方法
;
所用信息来源
??
System used for
categorization of severity levels; description of
consequences
to patients, users and
other persons
严重程度分类系统
;
对病人
,
用户和其它人所产生的后果描述
??
System used for
categorization of occurrence of each failure mode
(probability
estimate, frequency
expressed as e.g. ?events per device and
time?)
每种失效模式发生的分类系统
< br>(
可能性估计
,
频率表述为
”
根据器械和次数的事件
”
)
??
System used for
categorization of detectability of each failure
mode (criteria
for detectability,
frequency of in-process testing: 100%, sampling,
or no testing
i.e. validated process) <
/p>
每种失效模式的可检测性分类系统
(
可检
测性标准
,
进程内测试频率
:100%
,
抽样
,
或者无
测试
,
也就是经验证的过程
)
??
Method for combination of
severity, occurrence and detectability to risk
level
under consideration of the risk
definition (see ISO 14971 2.16) (e.g. diagram,
graph, formula)
在考虑风险定义
(
参见
ISO
14971
2.16)(
例如
:
图表
,
图形
,
公式
)
情况下
,
风险程度的严重
,
发生和可检测的组合方法
??
Criteria for risk
acceptability (e.g. acceptable, ALARP,
unacceptable) under
consideration of
the risk management plan and under consideration
of accumulated
risks
在考虑风险管理
计划和累计风险情况下
,
风险可接受性的标准
< br>(
例如
:
可接受
,
可操作又合
理的最低情况
,
不可接受
)
??
Note: If residual risks
remain in ALARP region a rational should be ready
to
substantiate that no further
mitigation was possible according to risk control
option analysis.
注意
:
如果剩余风险是在
”
可操作又合
理的最低情况
”
的范围内
,
应该根据风险控制选择分
析合理地证实没有其它的缓解措施
.
??
Result
(signed and dated documents): Risk
Management Report
结果
(
< br>文件上有签字
和日期
):
风险管
理报告
o
Hazards /
hazardous situations in normal condition
正常状态下的危害
/
危害性状
况
: list of applicable
hazards
列出适用危害
;
for each hazard (table format in
hierarchical structure, if applicable)
对于每一种危害
(
层级结构的表格形式
,
如果适用的话
)
??
List of potential worst
case effects (description of consequences to
patients,
users
and
other
persons
列出潜在
的最坏情况的影响
(
对病人
,
使用者和其他人所产生的
后果描述
)
??
List of potential causes
of hazards as
appropriate
适当列出危害的可能原因
??
Estimation of risk before
mitigation (severity, occurrence, risk) including
decision
on acceptability
缓解措
施前的风险评估
(
严重
,
发生
,
危险
),
包括可接受性的判定
??
Definition of risk
reduction measures including reference to
methods
(e.g.
design,
testing,
manufacturing)
and
results
of
verification
(implementation
and effectiveness)
风险降低措施的定义
,
包括方法
(
例如
:
设计
,
测试
,
制造
),
确认结果
(
实施和有效性
)
??
Estimation of risk after
mitigation (severity, occurrence, risk) including
decision
on acceptability under
consideration of the risk management plan and
under
consideration of accumulated
risks
在考虑风险管理计划和累计风险情况下
,
缓解措施后的风险评估
((
严重
,
发生
,
危险
),
包
括可接受性的判定
??
Risk / benefit weighting
under consideration of the state of the art
在考虑工艺状态情况下的风险
/
获益权衡
o
Hazards / hazardous
situations in fault condition
: list of
applicable failure
modes; for each
failure mode (table format in hierarchical
structure, if applicable):
在失效情况下的危害
/
危害性情况
:
列出
适用的实失效模式
;
对于每种失效模式
(
层级结构
的表格形式
,
如果适用的话
):
??
List of potential failure
modes
列出可能的失效模式
??
List of potential worst
case effects (description of consequences to
patients,
users
and
other)
列出潜在的最坏情况的影响对病人
,
使用者和其他人所产生的后果描
述
)
??
List of potential
causes of failures (as appropriate)
适当列出危害的可能原因
??
Estimation
of
risk
before
mitigation
(severity,
occurrence,
detectability,
risk)
including decision on
acceptability
缓解措施前的风险评估
(
严重
,
发生
,
可接受性
,
危险
),
包括可接受性的判定
??
Definition of risk
reduction measures including reference to methods
(e.g. design,
testing, manufacturing)
and results of verification (implementation and
effectiveness)
风险降低措施的定义
,
包括方法
(
例如
:<
/p>
设计
,
测试
,<
/p>
制造
)
和验证结果
(
实施和有效性
)
??
Estimation of risk after
mitigation (severity, occurrence, detectability,
risk) including
decision on
acceptability
缓解措施之后的风险估计
(
严重
,
发生
,
可检测
,
危险<
/p>
),
包括有关于可接受性的决定
.
??
Risk / benefit weighting
under consideration of the state of the art
在考虑工艺水平
情况下的风险
/
获益权衡
o
New
hazards:
Assessment of risks associated
with new hazards in normal and
fault
condition generated by risk mitigation measures.
Corresponding risk reduction,
if
applicable
新危害
:
评估
与在正常和失效状态下由风险缓解措施所产生的新危害有关联的危害
.
相
应的风险降低
,
如果适用的
话
.
??
Final
judgment, statement of
对以下内容的最终判断
,
陈述
:
o
Completeness of risk
evaluation
风险分析的完整性
o
Effectiveness of
mitigation measures including a link to the
verification documents
缓解措施的有效性
,
包括连接到验证文件
o
Overall acceptability of residual
risk
剩余风险的整体可接受性
o
Signed and dated by the team leader or
responsible person
团队领导或负责人签字
并署上日期
3. Drawings, Design-,
Product-Specifications
图纸
,
设计和产品规格
??
Comprehensive description
of the product
产品的综合描述
??
Components
and
materials:
complete
chemical,
biological
and
physical
char
acterization
部件和材料
:
完整的化学
,
生物和物理性特性描述
??
Photographs, Blueprints
照片
,
图纸
??
Functional
characteristics
and
technical
performance
specifications
such
as
mechanical,
physical,
electrical,
biological,
chemical,
sterility,
stability,
packaging,
transport,
storage,combination
with
other
medical
devices,
accuracy,
sensitivity,
specificity
of
measuring and diagnostic
devices, reliability
功能性特征和技术性能指标
,
例如机械的
,
物理性的<
/p>
,
电气的
,
生物
的
,
化学的
,
无菌性
,
稳定
性
,
包装
,
运输
,
存储
,
也其他医疗器械的组合
,
精确性
,
敏感性
,
测量和诊断器械的特异性
,
可
靠性
.
??
Other important
descriptive characteristics not detailed above
以上未详述的其他重要
的描述性特征
??
Design Control (brief
description)
设计控制
(
简单描述
)
??
QM (ISO 13485) Certificate
of design facility
质量管理
(ISO
13485)
设计设施证书
??
Final product release
criteria including reference to verification test
/ validation
4. Chemical,
Physical and Biological Tests
化学
< br>,
物理和生物测试
4.1
In Vitro Testing - Preclinical Studies
体
内测试
-
临床前研究
??
In general testing must be
conducted to predict the adequacy of device
response to
physiological and
pathological stresses, undesirable conditions and
forces, long-term
use and all known and
possible or foreseeable failure modes
一
般来说
,
测试必须能预测器械应对生理和病理应力
,
不利因素和外力
,
长期使
用和所有
已知的和可能的或可预见的失效模式的妥善性
??
Testing: e.g. visual,
chemical, biological, physical/mechanical testing
(i.e. tensile
strength,
durability,
corrosion,
fatigue,
long
term
stability),
efficacy
/
performance
testing,
simulated use
测试
:
例如视觉性
,
化学性的
,
生物性的
,
物理性的
/
机械性的测试
(
也就是拉力
,
持久性
,
腐蚀
性
,
疲劳
,
长期稳定性
),
效能
/
性能测试
,
模拟使用
.
??
Finite
Element Analysis if applicable
如果适用的话
,
有限元分析
??
Testing
shall
be
performed
on
finished
product
(devices
from
the
normal
manufacturing and
after sterilization)
应对成品进行测试
(
成品指正常生产的并经过灭菌的
)
??
Otherwise,
use
of
semi-finished
devices,
components,
or
raw
materials
must
be
characterized and justified
否则
,
使用半成品
,
< br>部件或原材料必须是并合法化的
.
??
Drug Compatibility:
Interaction between drug and device (e.g.
adsorption)
药物相容性
;
药物和器械之间的交互作用
(
例如
:
吸附作用
)
??
Test
protocols
测试协议
o
Purpose and objective of
testing
测试实物和目的
o
Standard applicability
matrix
标准适用性模型
??
List or table including
the full title, identifying numbers, date, and the
organization
that created the standard<
/p>
包括全称
,
识别号
,
日期和编制标准的机构的清单或表格
??
List of all
sections
列出所有的章节
??
Justification if
particular sections are not applicable
如
果特殊章节不适用的话
,
进行
证实
??
Reference to
verification test / validation
参考验证测试
/
确认
o
Justification if applicable standards
or parts thereof are not considered
如果可适
用
标准或部分标准没被考虑的话
,
进行
证实
??
If other
methods, such as internal standards are used,
these methods shall be
described in det
ail
如果使用其他的方法
,
例如内部
标准
,
这些方法要详细的进行描述
.
o
Accelerated and real time
ageing and simulated distribution (package
testing) prior
to testing. Otherwise a
justification is required
测试前的加速和实时老化以及
模拟分配
(
包装测试
).
另外需要证实
o
Conditions of accelerated
ageing
加速老化的条件
o
For each
test
对于每个测试
:
??
Parameters to be measured
and test description including reference to test
procedure if applicable
测量参数和
测试描述
,
如适用的话
,
包括测试程序
??
Measuring and testing
equipment
测量和测试设备
??
Calibration
arrangements
校准安排
??
Acceptance
criteria
验收准则
??
Number of test samples
including sample size rationale
被测样品数量
,
包括样品尺
寸基本原理
< br>
??
Test
reports
测试报告
o
Deviations and amendments to the
protocols and justification
偏差
,
协议和证实的修
正
o
Reference to raw data
including date, laboratory, location, engineer,
testing
equipment (device number and
calibration date)
参考原始数据
,
包括日期
,
实验室
,<
/p>
位置
,
工程师
,
测试设备
(
设备号和效准日期
)
o
Statistical
analysis
统计分析
o
Interpretation of data and
conclusion(s)
数据和结论阐述
o
Approval
signature(s)
批准签字
4.2 In Vivo Testing - Preclinical Studi
es
体外测试
-
临床前研究
Pre-clinical
animal
studies
used to support the probability
of effectiveness in humans
用于支持对人体的有效性的概率的临床前动物研究
??
Good laboratory
practice
良好实验室研究规范
??
Objectives,
methodology,
rationale
for
selecting
the
particular
animal
model
including
transferability to humans and limitations
< br>用于选择特殊的动物模型包括对人类的转移性和局限性的目的
,
< br>方法和基本原理
??
Results,
analysis
(also
statistical)
of
the
functional
effectiveness
and
the
device's
interactions with animal fluids and
tissues
功能性效果的结果和分析
,
< br>器械与动物流体和组织之间的交互作用的结果和分析
(
也
是统
计性的
)
??
Pharmacological
/
pharmacokinetical
/
toxicological
studies
i.e.
purity,
toxicity,
ADME (adsorption, distribution,
metabolism, elimination studies,
LD
50
)
药理学
< br>/
药动学
/
毒理学研究
,
也就是纯度
,
毒性<
/p>
,
ADME
(
即吸收、分布、代谢、排泄研究
,<
/p>
LD
50
)
??
Manufacturer's
conclusions
生产商的结论
4.3 Biocompatibility
Tests
生物相容性测试
The
documentation in support of biocompatibility shall
comprise the following:
??
Biocompatibility testing
plan
生物相容性测试计划
o
Purpose of the document, all applied st
andards
文件的目的
,
所有适用
的标准
o
Scope,
Description of the medical device
适用范围
,
医疗器械的描述
??
Intended
use
预期用途
??
List of
components/materials having direct or indirect
body contact
列出有直接或间
接的人体接触的部件
/
材料
??
Properties and
characteristics of the finished
product
成品的性能和特性
??
All materials used in the
manufacture, including auxiliary materials,
additives,
process contaminants and
residues, leachables, degradation products,
other components that do interact with
the final product, etc., or refer to the
applicable
section of the Design
Dossier
在生产中使用的所有的材料
,
包括辅助材料
,
添加剂
,
过程污染和残留物
,
滤除物
,
降解产物
,
其它与成品有交
互作用的部件等等
,
或者参见设计档案材料的适用章节
.
??
Where appropriate
define total surface area contacting the body or
body
Fluids
在适用的地方定义出与人体或人体流体
有接触的整个表面区域
??
Categorization of the
medical device based on ISO 10993-1: Tables 1 and
2
according to:
根据以下内容以
ISO 10993-1
为基础的医疗器械分类
::
表
1
和表
2:
??
Nature of body
contact
人体接触的性质
??
Contact
duration
接触持续时间
??
The category defines which
effects need to be considered at least
分
类定义至少哪些
效果需要考虑
o
Description of tested item(s) (finished
device, part of device, raw material)
测
试项目描述
(
成品
,
< br>器械部件
,
原材料
)
??
Testing shall be performed
on the final product or representative samples
taken from the final product or from
materials processed in the same manner
as the final product (if applicable
provide LOT/REF. No., etc.)
对从成品中或从以同样的
方式进行处理的材料中抽出的成品或代表性样品惊醒测试
(
如<
/p>
果适用
,
提供批号
/
参考编号等等
)
??
Rationale for the
selection of the sample
tested
被测样品选择的基本原理
??
Statement on the sterile
state of the test sample. If the test sample was
not
sterilized,
a
rationale
shall
be
given
why
sterilization
has
no
influence
on
biocompatibility of the final device
关于被测样品无菌状态的陈述．
如果测试样品不是无菌，
应给出灭菌对成品的生物相容
性不起作用的原因的基本原理．
??
Assign
appropriate
tests
to
the
biological
effects.
(Only
such
tests
shall
be
performed which lead to
evident results)
指定适当的测试来测试生物性效应（只进行此
类能产生明显结果的测试）
o
Overview of tests to be performed in
biological evaluation
在生物学评价中所进行的
测试的概观
??
The
selection and evaluation of any material or device
intended for use in humans
requires a
structured programme of assessment (refer to ISO
10993-1
Annex B)
用于人体的任何材料或器
械的选择和评估需要结构化的评估程序（参见
ISO
10993-1
中
附录Ｂ）
o
Justification for tests
not performed
未进行的测试的证实
??
The quality and the extent
of documentation as well as the assessment
in regard to the intended use determine
whether or not biological
tests shall
be performed with the final product and to what
extent
关于预期用途的文件材料的质量和范围以及评估决定了是否对成品进行生
物测试，
以及
进行到什么程度．
??
Biological evaluation may
include both a study of relevant experience and
actual
testing. Such an evaluation may
result in the conclusion that no testing is
needed if the material has a documented
history of use in a specified role that
is equivalent to that of the device
under design
生物评估包括相关经验和实际测试的研究．这样的评估可能
导致以下的结论：
如果材料有文件化的使用历史并在指定的作
用方面等同于正在设计中的器械的使用历
史，那么不需要测试．
??
Each device
should be examined on its own features. Data may
be available
from suppliers or in the
literature. In this case full transferability is
to be demonstrated.
Test systems, test
sensitivity and concentrations used should be
taken into consideration
每种器
械应根据其自身的特征进行检查．
可从供应商或文献中获得数据．
在此种情况下，
将展示完全的可转移性．应考虑到用过的测试系统，测试敏感性和浓度
．
??
Waiving of
tests shall be
recorded
弃权的测试应记录
??
Biocompatibility test
protocols
(copies)
生物相容性测试协议
(
复印件
)
o
Qualification of the test
laboratory, i.e.
accreditation
测试实验室的资格验证，即认证
o
Testing should be
conducted according to appropriate good laboratory
practices
followed by evaluation by
competent informed persons
测试应按照适当的良好实验
室规范进行，然后由权威的知情人士进行评估
o
For qualitative data: acceptance
criteria
对于定性数据：验收准则
??
Biocompatibility test
reports
(copies)
生物相容性测试报告（复印件）
o
For qualitative data/results:
interpretation
对于定性数据／结果：阐述
o
Positive results
–
What to
do?
阳性反应－要做什么？
??
Verification of
results
结果的确认
??
Chemical characterization
of leachables
滤出物的化学特性
??
Overall interpretation of
the biological evaluation of the device
器械的生物学评价的
总体阐述
??
Relevance of clinical
use
临床使用的相关性
??
Biocompatibility
evaluation and summary
report
生物相容性评价和总结报告
o
Compilation of tests
performed in tabular
form
以表格的形式编制测试
Example
例如
:
Test
测试
Protocol No.
协议号
Project No./
产品编号
Laboratory
No.
实验室编号
Report
date
报告日期
Result
结果
Conclusion
结论
Cytotoxicity
细胞毒性
Cytotoxicity test
/
细胞毒性测试
L
929-proliferation L 929-
扩散
XY yyyy-mm-
dd
年－月－日
Growth
analysis of cells cultured
with the test extract
showed no
relevant growth inhibition of
L929 cells.
测试提取的培养细胞的生长分析未显
示相关的
L929
细胞的生长抑制
Sensitization
致敏性
Murine Local
Lymph
鼠性局部淋巴
Node
Assay
节点化验
YZ
yyyy-mm-dd
年－月－日
The stimulation indices were
calculated to be less than
3.0.
刺激指数要少于
3.0.
o
Further relevant
information on the
tests
有关测试的更多相关信息
??
Test sample (part tested)
e.g. catheter shaft or tip, balloon, whole device
试样（部分测试）例如：管杆或
导管尖端，气囊，整个器械
??
Specification
(polymer type, supplier, trade name, additives)
e.g. PUR, Pellethane
2363-90A, 20%
Ba
2
SO
4
规格（聚合物类型，供应商，商品名，添加剂）例如：
PUR,
Pellethane
2363-90A, 20%
Ba
2
SO
4
??
Status of test
material (final product, sterile)
测试材料状态（成品，无菌）
??
Type of body contact e.g.
circulating blood
身体接触类型
例如：
血液循环
??
Contact duration e.g.
limited contact duration (< 24 h)
接触持续时间
例如：限定的接触持续
时间（＜
24
小时
)
??
Standard/norm e.g. EN ISO
10993-5: 1999
标准／规范
例如：
EN ISO 10993-5: 1999
??
Extract preparation
(medium, surface/mass to volume ratio,
temperature, time)
提取准备（媒介，表面／质量体积比，温度，时间）
??
Test lab qualification
e.g. competence under DIN EN ISO/IEC 17025,
certification
acc. to GLP
测试实验室资格
例如：
DIN EN
ISO/IEC 17025
的资格认证，依据
GLP
的认证
??
Action taken on positive
results as described above
上述的对阳性反应采取的措施
o
Conclusion
结论
??
Biological evaluation
shall be part of the risk management process
生物学评价应是风险管理过程的一部分．
??
A final statement of the
manufacturer is necessary. The manufacturer might
conclude that in his opinion, based on
the submitted documentation, the product
safety is ensured
生产商的最终陈述是必
要的．
生产商可能根据自己的意见，在所提交的文件材料基础上
得出产品安全是受到保障的结论．
4.4 Bio-
stability Tests
生物稳定性测试
Influence of the biological matrix on
the device, i.e.
生物基质对器械的影响，即
??
Surface Stress Cracking on
Polymers
高分子材料的表面应力断裂
??
Corrosion of load-bearing
metal screws
承重金属螺丝的腐蚀性
??
Coating
Stability
涂层稳定性
4.5 Microbiological Safety, Animal
Origin tissue
微生物安全
,
动物源性的组织
??
Geographical origin and
boarding of animals: Species, Country, Herd,
Feeding, Age
动物的地理来源：物种，国家，兽群，
饲养，年龄
??
Origin
of material used/nature of starting tissue:
所用材料来源／组织的性质
??
Specified risk material:
organ, tissue, body fluid
指定危险物质：器官，组织，人体流体
??
For TSE-relevant species:
If available certificate of suitability of
starting materials
with respect to TSE
issued by EDQM
对于与传染性海绵状脑病相关的物种：
如果可获得与由
EDQM
签发的传染性海绵状脑病
相关的原材料的适用性证书
??
Veterinary
controls
动物控制
??
Certificate demonstrating
conformance with veterinary inspection criteria
indicating
that the raw material was
fit for human consumption.
符合指示原材料适合人类消费的兽医学检测标准的证明证书
??
Certificate documenting
that the applied techniques for stunning and
slaughtering
were suitable to avoid
cross contamination with specified risk
material.(References:
EN 12442-2/SSC
guidelines/EC decisions.)
适用技术适合避免与规定的危
险物质交叉污染的证书记录
.
（参见：
EN
12442-2/SSC
向导
/EC
决定）
Risk analysis
风险分析
??
Risk
analysis
performed
according
to
EN
14971
and
EN
12442-1,
including
immunological,
toxicological, and liquid sterilization
risks.
按照
EN
14971
和
EN
< br>12442-1
所进行的风险分析
,
包括免疫学的
,
毒物学的
,
液体杀菌风
险
.
??
Sum of Category Numbers
(SCN) for TSE-relevant material only obtained
according
to
the following
scheme
与传染性海绵状脑病相关的物质的类别编号总概仅根据以下的模式包含在
内
:
Parameter Numbers of Risk
categories
风险类别的参数编号
1 2 3 4 CN
GBR IV
Incidence
发生率
< 1:10000
GBR III
Incidence
发生率
< 1:1 million
百万
GBR II
Others
其它
GBR I
No BSE, no
Risk
风险
Geographical
Origin
地理来源
Specified risk
High risk
Medium risk Low risk No
risk
规定的风险
高风险
中等风险
低风险
无
风险
Material
物质
Inactivation
钝化
None
无
2-4 log
4-6 log
> 6 log
Quantity/dose
> 100 g 1-100
g 10 mg
–
1 g < 10 mg
of raw material
原材料的数量
/
剂量
> 100 g
1-100 g 10 mg
–
1 g < 10 mg
Intracerebral
大脑内的
Other parenteral
其它肠胃外的
Mucous
membrane
黏膜
Route of
administration
给药途径
External
skin
外部皮肤
Sum of
Category Numbers (SCN)
类别编号汇总
:
Sum of
Category Numbers (SCN) Significance and Consequenc
es
类别编号汇总意义和
后果
20 Highest possible score, virtually no
risk
20
最高的可能得分
,
最终无风险
> 12
Acceptable risk, that is lower than the risk of
acquiring the sporadic form of human TSE
(CJD) >12
可接受风险
,
比获得人类
TSE (CJD)
零星形式的风险要低
10-12
Risk is acceptable only if the disease is serious
and
the benefit of the medical device
is high and scientifically
well-
established
10-12
只要疾病是严重的并且医疗器械的受益高且是科学确认的
,
那么风险是
可接受的
6-9
Unacceptably high risk
6-9
不可接受的
高风险
west possibly
score, unacceptably high risk
可能得分
,
不可接受的高风险
Documentation of significant processing
steps
重要工序的文件材料
??
A flowchart including the
starting material and all intermediate and
relevant process
parameters
such as temperature, duration, and pH
are required.
需要一个包含原材料和所有中介和相关的过程参数例如温
度
,
持续时间和
PH
< br>值的流程图
??
A
detailed description of the manufacturing process
including in-process controls
包括进程内控制的制造过程的详细描述
Procedure for reduction or inactivation
of potentially existing infectious agents
Documents
on
the
systematic
approach
to
gather
information
on
new
relevant
zoonoses and infectious agents:
减少或钝化可能存在的感染性因素的程序
系统方法来收集关于新的人畜共患病和感染性因素的信息的文件
:
< br>
??
A validation study on
virus inactivation / elimination including:
关于病毒钝化
/
消除的效度研究
??
A current literature
survey on relevant zoonoses
关于人畜共患病的现有文献调查
??
Information on the
production step with potential for inactivation
带潜在钝化的生产步骤信息
??
The study protocol
(including information on the test article, test
organism, rational
for the choice of
relevant or model organism, indicator cell, virus
titer, test method,
controls,
methods
for
calculating
the
results,
scaling
down,
interference
and
cytotoxicity tests)
研究协议
(
包括关于测试物体
< br>,
测试有机体
,
合理选择相关或生物模型
,
细胞的指标
,
病毒值
,
测试方法
,
控制
,
计算结
果
,
按比例缩小
,
干扰和细胞毒性测试
)
??
The final test
report
最终测试报告
??
The raw
data
原始数据
??
Such a study is
dispensable if the inactivation potential of the
processing step under
consideration is
well established in the scientific literature.
如果潜在的处理步骤钝化在科学的文献中很好地建立
,
这样的研究并不是必要的
.
Slaughtering, transport, and handling
屠宰
,
运输和处理
??
Include a statement and
respective certificates that requirements of
Regulation
1774/2002/EC are met, that
is: A certificate is required that the animals
have received
ante and post mortem
inspection by a veterinarian and were deemed fit
for human
consumption.
包括满足规
章
1774/2002/EC
要求的陈述和证书
,
即需要一个证书证明动物已经受到兽医
宰后检验
,
认为适合人类消耗
.
??
Traceability, e.g. a
lot-wise documentation of individual animals
可追溯性
,
例如
:
个别
动物的文件资料
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