变更控制管理规程-中英文

2021年1月26日发(作者：冰橇)


文件名称
File
Name

变更控制管理规程

Change Control
Procedure

审核人
/
日期
Checked

By/Date
批准人
/
日期
Approved

By/Date

文件编号


SOP-Q00011.05
File No.
执行日期

Effective Date

起草人
/
日期

Prepared By/Date






1
目的

建立正式的变更控制系统，以评估可能影响中间体或成品生产和控制的所有变更。

PURPOSE
To establish an official change control system to evaluate all changes that may
affect the production and control of the intermediates or final product.
2
范围

本标准适用于公司生产品种变更的评价和变更过程的控制和管理。

SCOPE
It applies to evaluate the changes of products and to control and manage the change
process.
3
责任

RESPONSIBILITY

QA
部负责变更的管理和复审，
QA
部经理负责变更的批准；


QA Department should manage and review the changes; QA Manager is responsible for approving
the changes.

生产部门负责生产变更的申请及实施和管理；

Production department should apply, implement and manage the changes of production.
QA
负责质量标准变更的申请及实施和管理；


QA should apply, implement and manage the quality specifications changes.
QC
负责分析方法变更的申请及实施和管理；


QC should apply, implement and manage the changes for analysis methods.
设备部
/
工程部负责设备与设施的变更管理与申请；


Equipment/Engineering department should apply and manage the changes for facilities, support
systems and equipments.


采购部负责物料变更管理与申请；

Purchase department should apply and manage the changes for materials.
质量管理部负责向国内药政机构如
SFDA
传递相关信息；

QA department should report the relevant information to domestic authorities (such as SFDA).
外贸注
册部负责向国外药政机构如
FDA
、
EDQM
及持有
DMF
资料的客户传递相关信息；

Regulatory Affairs Department should report the relevant information to the oversea
authorities (such as FDA
、
EDQM) and DMF related customers.
销售部门负责向其他客户提供变更的有关信息。

Sales Department should report the relevant information to other customers.

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4
定义

DEFINITION

变更是指药品生产质量系统各要素的改变。


Change means any alteration occurred in the production and quality system.
5
引用标准

REFERENCE
ICH
Q7a 13


6
适用范围
PLICABLE SCOPE

6.1
原料变更
(
包括供应变更
)
Changes of raw materials (including the supplier changes);
6.2
质量规格变更

Changes of specifications
6.3
分析方法变更（包括检测条件，法定对照品批号的变更）


Changes of analysis methods;(including the changes of either test conditions or batch No. of
primary reference standards obtained from an officially recognized source)
6.4
设备与设施的变更


Changes of facilities, supporting systems and equipments;
6.5
工艺变更


Changes of the manufacturing processes;
6.6
包装材料与标签的变更


Changes of labeling and packaging materials;
6.7
计算机软件的变更


Changes of computer softwares.
6.8
COS
或其他证书持有人改变


Changes of holders of COS or other certificates
6.9
生产场地的改变


Manufacturing site Changes
6.10
产品批量增大与缩小

Increasing and decreasing for the batch size.

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6.11
化学纯度和微生物质量证书的变更


Changes of certificates for chemical purity and microbiological quality.
6.12
TSE
证书的变更


Changes of TSE certificates.


7
变更的类型
CLASSES OF CHANGES

根据变更的对生产工艺和产品质量
(
中间体
)
的影响程度，变更可分为关键、一般和

微小变更三类。

According to the influence extent to the manufacturing process and product (intermediate) quality,
the changes is classified as critical change, major change and minor change.
7.1
关键变更：对中间体或成品质量有影响的变更，对质量影响分为降低，等同，提高。


Critical changes: the changes which will impact the intermediates or final product
’
s quality. The

impact to quality may be classified to reducing, equivalent, improving.
7.1.1
主要工艺路线及原料、辅料成份
(
处方
)
的改变。


Changes of the major synthesis process and ingredients of raw materials and excipients, such
as formula.
7.1.2
化学合成、精制所使用的起始物料和关键原料的改变。


Changes of the starting materials and critical materials used for chemical synthesis and
purification
。

7.1.3
厂房或生产地址的变更。


Changes of buildings or manufacturing sites.

7.1.4
生产设施和设备的更新或扩容。


Changing or extending the capacity of the manufacturing facilities and equipments.

7.1.5
产品内包材的变更。



Changes of product
’
s primary packaging materials.
7.1.6
关键工艺条件和参数的改变，例如：消毒工艺、温度、压力、通气量、时间等。

Changes of the critical process conditions and parameters, such as: disinfective method,
temperature, pressure, ventilation volume, time etc.
7.1.7
关键原材料、中间体、成品以及过程分析的分析方法的删除。


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Deleting the analysis procedure for the critical raw materials, intermediates, and final products.
7.1.8
产品质量标准的变更

(
不包括限度标准的提高
)
。


Changes of the product
’
s specifications.(excluded the tightening of limits)

7.1.9
精烘包工艺路线的变更。


Changes of the purification, drying and packaging process.

7.1.10
对药典已收载的分析方法的改变。


Changes of the analytical methods which has been adopted in the pharmacopoeia.

7.1.11
对成品标签内容大幅度的改变。


Greatly changes of the label content for finished products.
7.1.12
非关键工艺条件和参数的变更，如合成、提取精制用原料、溶媒的调整以及加料顺

序的改变等。

Changes of non-critical process conditions and parameters, such as: the adjustment of raw
material and solvent in the synthesis and extraction, the changes of material loading
sequence.
7.1.13
在工艺规程范围内改变控制参数至更严格的范围或采用新的准确度更高的中间体检

验方法。


Changes to stricter control parameters but still within the range of established process
procedures, or changes of adoption new and more accurate testing method for intermediates.

7.1.14
最终制造中使用的物质来源由植物或合成物变为
TSE
风险物质的变更。

Changes of the sources of materials used in the final manufacturing process, but turn from
plants or compounds sources into TSE risk substances


7.1.15
化学纯度和微生物质量风险提高原因对证书的变更。

COS changes caused by rising quality risk of chemical purity or microbiological quality.
7.2
一般变更：对中间体或成品质量没有影响的变更。


Major changes: the changes which will not impact the intermediate or API
’
s quality.

7.2.1

原料药精烘包工序生产线使用同类型或相似的设备，或产品批量变更< br>(
数量级内
)
。

Changes of product batch size(within the order of magnitude), or changes that use the same or
similar equipment in the process of purification, drying and packaging.

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7.2.2
产品外包材的变更。

Changes of the secondary packaging materials.
7.2.3
标签小幅度的变更。


Small changes of labels.

7.2.4
生产辅助设备（动力中心、计量器械）的变更。


Changes of manufacturing support systems (power center, calibration instruments).

7.2.5
生产及质量管理用的计算机软件的变更。


Changes of computer software which are used for manufacturing and quality managing.

7.2.6
产品的仓储条件及运送方法等的变更等。

Changes of storage condition and shipping ways.

7.2.7
同一生产线增加品种，经验证对原产品质量无影响。

Add another new product in a manufacturing line, which has been proved to be no effect on the
original product after validation.
7.2.8
有效期
/< br>复检期已在适应性证书中提及，或要求在适用性证书中包含有效期
/
复检期时，

对最终产品的有效期
/
复检期或贮存条件进行变更；


Changes of the product expiry period/retest date or store conditions on the COS, which may
have already stated on the certificate, or ask for adding these items on it.
7.2.9
适用性“
双重
”
证书
（化学纯度和微生物质量适用性证书及
TSE
风险适用性证书）
产品

制造中使用的物质来源由
TSE
风险物质变为植物或合成物；


The sources of materials involved in manufacturing the APIs referred in the double COS (COS
of both chemical and TSE risk type), changed from TSE risk materials to plant or compound
materials.
7.2.10
生产过程中使用的起始物料、关键物料或中间体的制造商的变更或新的制造商的增加；

Changes of the suppliers of starting materials, critical materials or intermediates for the
manufacturing or adding a new supplier.
7.2.11
用于合成最终产品的非关键物料、中间体
/
试剂的质量标准： 新检验参数的增加或检

验程序的变更；

Changes of quality specifications for the non-critical materials, intermediates or solvents for
synthesizing the APIs, such as adding new test items or changing test procedure.

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7.3
微小变更：对中间体或成品质量没有影响。

Minor changes: the changes which will not impact the intermediat
es’ or
APIs
’
quality.

7.3.1
新增生产工艺过程中的检测。

Adding new testing items in the process control.

7.3.2
由于药品各药典或国家标准升级改版而进行的更改。

Changes due to pharmacopoeia version upgrade or national standards upgrade.

7.3.3
修改非关键原料的分析方法。

Modifying analysis methods of non-critical raw materials.
7.3.4
公司机构和人员的变化。


Changes on company
’
s organization and personnel.

7.3.5
TSE
风险证书，来源国删除或对将最终产品制造中使用的物质的来源由
TSE
风险物

质变为植物或合成物质；

For the TSE risk type COS, the original country was deleted or the source of materials used in
the manufacturing of the APIs was changed from TSE risk material into plant or synthesis
material.


7.3.6
证书持有人或最终产品制造商的名称和
/
或地址的变更。

Changes of holders of the COS or manufacturers
’
name and/or address.
7.3.7
生产地点的名称和
/
或地址名称的变更。


Changes of the name or address of manufacturing sites.

7.3.8
非关键原料供应商的改变


Changes of non- critical raw material
s’ s
upplier.

7.3.9
产品或最终产品生产过程中使用的起始物料
/
中间体
/
试剂的检验程序的次要变更

（如柱子长度，标准品批号变更等）；


Subsidiary changes of the test procedure of starting material or intermediate or solvent
introduced in the manufacturing. (Such as column length, batch No. of reference standard)


7.3.10
最终产品、及最终产品生产中使用的起始物料
/
中间体
/
试剂的质量标准限度的加强；

Changes of tightening of the acceptance criteria limits of APIs and the starting material
/intermediate/solvent in the process of the APIs.

7.3.11
最终产品或在最终产品合成中使用的任何物料的产品< br>/
对照品代码和
/
或商标名的变更；


Changes of the product code No., RS code No. or trade name of products or any material

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used in the process of the APIs.
7.3.12
适用性证书批准时对稳定性数据及承诺进行的修改；


Changes of modifying the stability data and stability commitment when the COS is under
approving.
7.4
其他未包括在以上范围内的变更，根据评审结果确定，由
QA
部经理批准变更类型并实

施相应的管理。



For the changes out of the above scope, QA Manager should approve change
’
s classes and
implement the relevant managements according to result of the review.


8
变更流程
Change Procedure

8.1
变更控制的总体要求：所有变更均应按相应的管理规程进行，作有计划的变更，防止对

已验证的系统设备、工艺和主要原料进行未批准的自行变更。

General requirements for change control: all changes should be proceeded according to the
relevant management procedures. Planned changes should be dealt to avoid any self-change to
validated system equipment, process and critical raw materials without authority.


8.2
变更管理的程序：

Change management procedure
见《变更流程图》。


See .

8.3
变更申请表的起草、审核及批准


Preparing, reviewing and approving of the change application table


8.3.1
生产变更由生产部起草
“
变更申请表
”
提交变更方案。

Manufacturing Department should draft
“
change application tabl
e”
and submit change
protocol for manufacturing changes.

8.3.2
质量标准的变更由
QA
起草
“
变更申请表
”
，提交变更方案。


QA
should
draft
“
change
application
tabl
e”

and
submit
change
protocol
for
specification

changes.

8.3.3
分析方法的变更由
QC
起草
“
变更申请表
”
，提交变更方案。


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