-
STANDARD OPERATING PROCEDURE
标准操作规程
Title : QUALITY DEVIATION
MANAGEMENT
题目：质量偏差管理
Effective
Date:
生效日期
:
Prepared by
准备
QA
Documentation that may be
affected:
其他可能受到影响的文件
:
Out of Specification
Results
“OOS”
超出质量
标准的实验结果
Quality
Alert Management
质量警戒的管理
Change control
改变控制
Quality risk
assessment
质量风险管理
Reviewed
by
审阅
QA
Procedure:
编号
:
Review
Date:
复审日期：
Supersedes:
替代
:
Approved
by
批准
IQC Manager
质量部经理
Review of
Corrective and Preventive Action (CAPA) Programs
纠正及预防措施的回顾
Unmodified Review History:
无变更的复审记录
:
Reviewed By/ Date
复审
/
日期
Affected
Department / Area
:
Approved by IQC Manager/
Date
质量部经理批准
/
日期
Next Review Date
下次复审日期
受影响的部门
/
区域
:
1.
PURPOSE
目的
Whenever a
product, material or system fails to meet the
specifications or in the event of a failure to
comply with relevant documentation or
regulatory requirements, an appropriate
investigation must be
undertaken, the
cause(s) identified and the necessary corrective
actions taken
当产品、
物料或系统不符合质量
标准要求或某事件不符合相关文件或法规要求时，
必须进行适当
的调查，查明原因并采取必要的改正措施。
2.
SCOPE
范围
This
SOP
covers
all
failures
and
unplanned
incidents
related
to
Chemical
components,
Packaging
materials, Drug
Products, Processes, Systems, Equipments,
Utilities and Facilities used to produce and
control them.
本
SO
P
适用于处理所有失误及非计划性故障事件，含概用于产品并控制产品的化学成分、
包装材料、药品、工艺、系统、设备、公共设施和厂房等。
3.
DEFINITIONS/ABBREVIATIONS
定义
/
缩写
during
manufacturing
or
testing
or
a
non-conformance
to
approved
specifications
or
any
failure on GMP-related
systems. Deviations are assessed according to
compliance and /or
the risk they
present to patient health and/or with regulatory
requirements. Deviations are
to be
classified as
“
critical or
major or minor
”
Deviation
（
also
known
as
anomaly<
/p>
）
：
Any
unplanned
change
from
a
written
procedure/document,
偏差（通常也称为
异常）
：
在药品生产过程中，任何与既定的程序、文件不符的非
计划的变更或
与批准的质量标准不符，或与
GMP
相关的系统失败。偏差按照对患者造成的风险何
国家法规的符合性进行评估。
偏差可分为三类“严重偏差、主要偏差、微小偏差”
Critical Deviations:
严重偏差：
Critical
deviations
require
immediate
investigation,
root
cause
analysis
and
corrective-preventive action.
严重偏差需要立即进行调查，查找问题的根本原因并制定纠正预防措施。
A
deficiency
in
material,
drug
product,
medical
device,
system
or
service
that
can
affect
significantly the
quality, purity, safety or efficacy of a
product/medical device or can lead
to
health
threatening
conditions
in
drug
product,
or
medical
device.
Alternatively,
any
deficiency that can lead to a non-
compliant drug product/medical device or to a
situation
that may be cited by
regulatory authorities as critical.
存在物
料、
产品、
医疗器械或任何系统、
维护
方面能严重影响产品质量、
纯度、
安全、
功效，
能对产品或身体健康产生危害的缺陷；
或者会导致产品
质量不符合，
或可能被
法规部门视为严重缺陷项的缺陷；
Major Deviation:
主要偏差：
Major
deviations
require
investigations,
root
cause
analysis
and
corrective-preventive
action.
主要偏差需要进行调查，查找问题的根本原因
并制定纠正预防措施。
A non-critical
deviation which potentially affects the quality,
purity, safety or efficacy of a
product/medical device or ability to
meet GMP requirements.
非严重偏差可能潜在影响产品的质量
、纯度、安全、功效或
GMP
法规的依从性。
< br>
Minor
Deviation
：
微小偏差：
Minor
deviation require investigation, root cause
analysis and corrective-preventive action.
微小偏差需要调查，查找问题的根本原因并制定纠正预防措施。
A
deviation
not
classified
as
critical
or
major,
which
potentially
impacts
a
GMP
system,
utility, equipment, material,
component, environment or documentation, but does
not affect
product/medial device
quality, purity, safety, or efficacy.
潜
在影响
GMP
系统，公用设施，设备、物料、成分、环境或文件
，但不影响产品的质
量、纯度、安全、功效，不属于严重及主要偏差的缺陷。
Deviations will typically, but not
exclusively, fall into one of the following
categories:
?
Confirmed Out of Specification (OOS)
test results
?
Controlled Zone Environmental results
outside of limits
?
Failure to comply with instructions in
standard documents (Deviation from Standard
Operating Procedures, Deviation from
Batch processing parameters during
Manufacture, Packaging, labelling or
Testing)
?
Process or equipment failure which
affects product quality
?
Reconciliation
or yield outside Specification
?
Failure to
comply with established program (calibration,
preventive maintenance and
stability
test, etc)
?
Material damage or contamination in
storage or handling
偏差通常，但不绝对，发生在以下几个类别中
:
?
确认的超出标准的测试结果
?
受控区域环境超标
?
不符合标准文件规定的操作（不符
合标准操作规程的操作，生产、包装、贴标
签或测试过程中操作参数的错误等）
?
影响产品质量的操作失误或设备故障
?
物料平衡或产率超过限度
?
物料在储存或处理过程中出现的损坏和污染情况。
?
活动未能按照计划进行（校准，预防性维护及稳定性试验等）
4.
SAFETY
安全
N.A.
无
5.
PROCEDURE
程序
5.1
RESPONSIBILITIES
责任
5.1.1
Manufacturing,
Logistic, Engineering,QC,HR
Managers
生产、物流、工程部、
QC
、
HR
经理
?
It is their responsibility to
immediately notify to QA of the occurrence of any
event that
could
lead to a potential failure event and
to actively participate in investigation process
其职责为当那些可能导致潜在失误事件发生时，立即通知
QA
，并积极参与调查
活动。
?
?
Initiate the Quality Deviation Report.
起草质量偏差报告
Implementing corrective
action resulting from deviation reports when
approved by the Head
of Quality .
执行质量部经理批准的偏差改正措施。
?
Ensuring all
personnel in their Department are trained in the
content of this SOP and know
that all
quality deviations are to be reported.
确保本部门人员接受本
SOP
的培训并清楚所有需要报告的偏差
。
5.1.2
?
?
?
?
Site
IQC manager
is responsible for
质量部经理负责
Ensuring
that this SOP is maintained and complies with
corporate and local GMP standards.
确保本<
/p>
SOP
始终符合集团及中国
GMP
的要求。
Approval of
corrective action resulting from deviation
reports.
批准偏差的改正措施。
Approval the disposition of the batch
in case of Batch deviations.
当发生批生产偏差时决定批次的处理。
Site IQC Manager is responsible for
further communication to the impacted unit and to
the
respective Operational Industrial
Quality and Compliance (IQC) management If the
failure or
deviation is critical or if
other sites/sub-contractors are potentially
impacted.
如异常事件或偏差程度严重或其他工厂或下级合同商可能受到影响
，工厂质量部经理负
责与受影响的单位以及相关区域质量运营部进一步沟通。
?
For
critical deviations affecting product on the
market, please follow the SOP
“
Quanlity Alert
Management
”
,site
IQC Management is responsible to involve
Industrial Quality and
Compliance/Risk
Management to ensure the consistent handling of
such critical deviations.
对
于影响到市场产品的严重偏差，按照“质量警戒的管理”，由质量部经理负责利用风
险评
估系统向
IQC
通报以确保类似严重偏差处理的一致性。
5.1.3
?
QA is
responsible for QA
负责
Assure that the appropriate
investigation is conducted
into any failure and that an
investigative report is
issued to document the situation according to the
requirements of this
SOP
确保每个偏差都进行了适当的调查，并按本
SOP
< br>要求发放偏差报告。
?
?
?
?
5.1.4
?
QC
manager is responsible for
QC
经理负责
Ensuring
all test result deviations are reported according
to SOP S-QC035, Out of Specification
Results “OOS”.
确保按照
SOP
S-QC035
报告实验结果发生的偏差。
?
Perform all the
tests requested by the investigation report to
investigate the cause of the deviation
and/or the quality of the product.
进行调查所需的测试以配合查明原因或确定产品质量。
?
5.1.5
?
?
All Department Personnel are
responsible for
所有人员负有如下责任
Reporting all quality deviations to
their Department Supervisor or Department Head.
向部门主管或部门经理报告所有质量偏差。
Ensure communication to
Health, Safety and Environment (HSE) if the
deviation may have an
impact on HSE
matters.
如果偏差可能影响到
HSE
确保通知健康、安全、环境部门。
Reviewing all OOS of the year at least
annually and producing a report showing trends
etc.
至少每年进行一次当年所有
OOS
< br>的审阅并作趋势分析等。
Maintaining a
log of all deviation reports.
保管登记所有偏差报告的日志。
Filing a copy of all deviation reports.
将偏差报告存档
Following
up reports ensuring that they are closed out in a
timely manner.
跟踪偏差报告确保它们及时结束。
Reviewing all deviations of this year
at least annually etc.
至少每年进行一次当年所有偏差的审阅等。
5.2
Reporting of
Quality Deviations
质量偏差的报告
5.2.1
Planned
Deviations
计划性偏差
Planed Deviation must not be done on an
ongoing basis but exceptional use only.
计划性的偏差只能作为非常规的特例使用。
Planed Deviation must be
pre-authorized by QO Manager.
计划性的偏差一定要被质量部经理预先授权认可。
Documentation of the
purpose of the deviation and approval by QO
Manager is required.
要求书面记录偏差的目的以及经质量部经理批准。
5.2.2
Unplanned Deviations
非计划性偏差
All
instances
of
quality
deviations
must
be
reported
immediately
to
the
relevant
area
Department
Manager or
Supervisor.
所有质量偏差
必须
< br>立即向相关的部门主管或经理报告。
The
area
Department
is
to
initiate
the
Quality
Deviation
Report
using
the
form
shown
in
the
Attachments section of
this SOP.
偏差发生部门负责起草质量偏差报告（
见本
SOP
附件）
5.2.3
Principles
and methods
偏差处理的原则及方法
5.2.3.1
Deviation
initial
偏差发起
The following guidelines are given to
assist completion of the report.
以下方针用以协助报告的完成
1.
The
Manager/Supervisor or the operator of the
Department where the deviation occurred is to
complete the following details in the
sections 1, 2,3
：
发生偏差的部门的经理
/
主管或发现偏差的操作人员应填写第<
/p>
1
、
2
、
3
、部分：
In the section 1:
第
1
部分
-
-
-
In
the section
2:
第
2
部分
-
Product name
and batch number if it is a Product failure,
Equipment name if one
equipment failure
or Utility name if the failure affected one
utility.
若是产品偏差，记录发生的产品名称和批
号；如果是设备误差，记录设备名称；如
果是影响到公共设施的偏差，记录受影响的公共
设施的名称。
In the
section 3:
第
3
部分
-
Detailed
explanation of the incident and the other
products/batches can be affected in their
quality.
Department name
部门名称
Date raised
发现日期
Raised by
(name)
发现者（姓名）
<
/p>
误差事故的详细描述及可能影响到质量的其他产品
/
批次。
-
Report every
immediate action which is approved by department
manager or supervisor
after deviation
found.
报告偏差发现后采取的每一个部门经理或主管批准的紧急措施。
5.2.3.2
Deviation Evaluation
偏差的评估
After completion of these steps the
Quality Deviation Form has to be given to QA to: <
/p>
在这些质量偏差报告步骤完成后交给
QA
以进行：
-
QA should make
a decision whether it is
necessary to quarantine product or
materials if
the deviation is product
or material related. The decision shall be filled
in section 3 as an
immediate action.
如果偏差与产品或物料有关，
发生后
QA
应立即决定是否需要立即将产品或物料
“待
检”起来。决定应被记录在第
3
部分作为一项紧急措施。
-
-
Call and
organize a meeting with the involved Department
Manager / Supervisor and all
other
functions that can help in discussing and set the
investigation to find the cause(s) of
the failure/deviation
召集所有相关部门的经理
/
主管以及其他对于讨论
并找出偏差的原因有帮助的职能
部门人员开会。
-
During the investigation the extent of
the problem, for example, implications for
previous
or subsequent batches of the
same/other product(s) should be taken into
consideration, as
well as, depending on
the nature of the deviation, it may be necessary
to execute
additional stability studies
and so on.
Report the
investigation observation in the section
5 of the form Quality Deviation Report.
Attach to the form all the memos, e-mails and so
on related to the problem.
在
调查过程中，要考虑问题的扩展程度，比如是否牵涉相同
/
不同
产品的前几批或后
几批；还有，依据偏差的性质，可能需要进行额外的稳定性试验等。在
质量偏差报
告的第
5
部分报告调查的发
现。将所有与调查有关的备忘、电子邮件等等附在报告
上。
The
deviation
evaluation
is
based
on
the
comparison
to
the
safty
risk
evaluation
and
capability to detect the
defect
偏差评估应基于对质量安全风险的评估及缺陷被
发现的可能性的综合评价。
The
severity of the impact is defined as per below
descriptions:
严重性等级分类描述如下：
Fill the section 4 and
record in the Deviations logbook.
填写第
4
部分并在日志中登记。
Rating
Classification
等级
分类
1
Minor
微小
2
Moderate
一般
4
Major
关键
5
Severe
严重
Description
描述
Compliance
with
dossier/cGMP
but
increase
risk
for
complaints
符合注册文件及现行
< br>GMP
的要求，但增加投诉的风险
Or/and
defect
leading
to
products
that
do
not
cause
any
adverse
health
reaction.
They
may
pose
a
constraint
for
the
user or may impair the
market imagine of the products.
和
/
或缺陷导致产品不会对健康产生任何不良影响，但可能
致产品使用受到限制或影响产品形象。
Non
compliance
with dossier /cGMP no or
minor influence
on product
quality(safety ,
efficiency)
；
不符合注
册文件或现行
GMP
要求，
对产品质量
无影响或微
小影响；
Or
and
defects
,which
may
not
pose
a
significant
hazard
to
health
but
where
a
recall
could
be
initiated
(perhaps
not
required by the
competent authority) for other reasons, but are
not class 1 or 2;
和
/
或缺陷，不会对健康产生严重影响但可能会因其他原因
发
起召回（可能不会被法规部门要求）
，但不属于
1
、
2
类
缺陷；
A
situation
in
which
use
of
or
exposure
to
a
compromised
product is not likely to cause adverse
health consequences
；
使用或让步使用的情形不会对公众健康产生不良影响；
Non
compliance
with
dossier
/cGMP
;
major
influence
on
product quality(safety ,
efficiency)
；
不符合注
册文件或现行
GMP
要求，
对产品质量
（安全、
功
效）产生重大影响；
Or and defects ,which could
cause illness or mistreatment, but
are
not class 1;
和
/
或缺
陷，
可能导致疾病或错误治疗，
但不属于一类缺陷；
A
situation
in
which
use
of
or
exposure
to
a
compromised
product may cause temporary or
medically reversible adverse
health
consequences is remote
；
使用或让步使用的情形对患者健康产生临时或可逆的治疗
不利影响的可能
极小；
Non
compliance
with
dossier
/cGMP
;
critical
influence
on
product quality(safety ,
efficiency)
；
不符合注
册文件或现行
GMP
要求，
对产品质量
（安全、
功
效）产生严重影响；
Or/ and defects ,which are
potentially life
threading or could
cause serious risk to health;
和
/
或缺陷，对生命存在潜在威胁或可能导致对健康产生严
重风险；
A situation
in which there is a reasonable probability that
the
use
of
or
exposure
to
a
compromised
product
will
cause
serious adverse health consequences or
death.
有依据可证明使用或让步使用的情形对健康产生严重不良
影响或致死；
The occurrence definitions are
proposed:
可能性分类如下：
Rating
等级
Occurrence
可能性
Extremely
rare/very
1
unlikely
极少
/
几乎不可能
Very unlikely
几乎不可能
First time
that the event is observed
第一次发现此事件
Rare
2
Remote/rare
微乎其
微
/
很少
很少
Isolated in
the concerned batch
在相关的批次中独立
Possible, do not expect reoccurrence
可能，不希望再次发生
3
Occasional
偶尔
Event
observed
0
to
1
time
a
month/a
campaign
or/and
isolated
cluster
in
the
concerned
batch
在一个月内或一个批组内内发生
0-1
次的事
件，或在不连续的批次内发生。
Probable, possible reoccurrence
很可能，可能再次发生
4
Likely
可能
Event
observed
2
to
3
times
a
month/a
campaign
or/and
Unpredictable
number
of
units impacted in the
concerned batch
在一个月内或一个批组内内发生
2-3
次的事
件，
或在相关的批次
内不可预知发生的次数。
Frequent to
permanent, or unknown occurrence
Almost
certain or unknown
5
几乎肯定会发生
/
不能确
定
频繁固定的发生，或不可知发生性
Event
observed
4
to
5
times
a
month/a
campaign
or/and
previous
and/or
following
batches also
impacted.
在一个月内或一个批组内内发生
4-5<
/p>
次的事
Description
描述
件，或在后续的批次也深受影响的。
The safety risk level is
given by multiplying the severity of impact and
the likelihood of occurrence.
The
result is compared to the following chart:
质量风险严重等级来自于缺陷的严重性及发生的可能性的乘积，结论见下表：
Likelihood of
Occurrence
Almost
certain
or
even
5
10
20
25
unknown
5
Likely
4
Occasional
3
Remote
2
Extremely
rare
1
4
3
2
1
Based on the results given in the above
chart, the safety risk level is evaluated:
Low if the number is
＜
4
（
green
area
）
Moderate if
the number is
＞
3 and
＜
10 (orange
area)
High if the number is
＞
8 (red area)
根据上表，质量风险严重等级为：
如
果乘积小于
4
（绿色区域）为低；
<
/p>
如果乘积大于
3
而小于
< br>10
（黄色区域）为中；
如果
乘积大于
8
（红色区域）为高；
The Detection definitions are proposed:
可发现性分类如下：
Rating
等级
Detection
可发现性
100%;
100%
控制性能指标，
检查接近
100%
High probability to
detect and reject the defect
发现并剔除缺陷产品的可能性很高；
100%c control with a performance
significantly
2
moderate
different
to
100%
or
partial
control
(e.g.
IPC,
statistical);
100%
控制性能指标，大量检查但不能
100%
Description
描述
100%
control
with
a
performance
close
to
1
High
高
8
6
4
2
16
12
8
4
20
15
10
5
Minor 1
Severity of impact
Moderate
2
Major 4
Sever
5