变更控制管理规程
Change Control Management
1 目的/Purpose
建立变更控制管理体系，对与产品质量有关的变更进行控制、评估和管理，从而保证产品的质量、有效性和安全性。
This document describes the procedure to control, evaluate and manage the changes that have an impact on product quality in order to assure the quality, efficacy and safety product.
2 范围/Scope
2.1 本规程适用于可能影响产品质量的所有变更，但不仅限于：
This procedure applies to all changes that may affect product quality, including but not limited to the following:
●主要原辅材料Key Raw Materials.
●设备和分析仪器Equipment and Analytical Equipment.
●设施Facilities.
●公用系统（如水系统、压缩空气系统等）
Utilities (e.g. water system, compressed air system, etc.)
●产品生产工艺Manufacturing Processes
●清洁工艺Cleaning Methods
●质量标准Specifications
●检验方法Analytical Test Methods
●计算机硬件和软件Computer Hardware and Software
●生产地址Manufacturing Site
2.2 本规程不包括文件变更。文件变更按照《文件管理规程》执行。
This procedure excludes the Change Control of documents which is described in “Document Management”.
2.3 本规程不包括供应商变更。供应商变更按照《供应商评估与选择管理规程》执行。This procedure excludes the changes in suppliers which is governed under “Supplier
Evaluation and Selection”.
2.4 本规程不包括标签和包装材料变更。标签和包装材料变更按照《产品包装设计、印刷管理规程》执行。
This procedure excludes the changes in labels and packaging materials which are governed under “Management of Packaging Material Design & Printing”.
3 职责/Responsibilities
3.1 变更申请人/Applicant of Change
●提出变更申请Raise the change application
●提供变更申请和变更实施所需的支持性材料
Provide supporting materials for application and implementation of change.
●拟定变更的实施日期Propose the implementation date
●参加与所提交变更相关的评估会议
Participate in the assessment meeting regarding the change
●编写风险评估报告（如需要）Generate a risk assessment report if required
●制定变更实施计划，跟踪变更进度
Establish the change implementation plan, track change schedule
3.2 生产车间/Workshop
●评估变更对产品质量的影响Evaluate the impact on product quality
●评估变更对本部门GMP文件的影响
Evaluate the impact on the associated department’s GMP documentation
3.3 国际部/International Dept.
a) 评估对国外客户的影响Evaluate the impact on foreign customers
b) 评估对国外注册资料的影响Evaluate the impact on the foreign registration
file
3.4 物流部/Logistics Department
●评估对物料/产品存储、发运的影响
Evaluate the impact on storage and distribution of Material/product
●评估变更对本部门GMP文件的影响
Evaluate the impact on the associated department’s GMP documentation
3.5 研发中心/Research& Development Center
●评估对注册资料的影响Evaluate the impact on the registration file
●执行注册补充申请工作（如需要）
Prepare and submit the supplementary registration document to the competent authority where applicable
3.6 公共支持部/Utilities Support
●评估对变更设备运营和维护保养的影响
Evaluate the impact on the operation and maintenance of equipment to be changed
●评估变更对本部门GMP文件的影响
Evaluate the impact on the associated department’s GMP documentation
3.7 销售中心、销售部/Sales Center& Sales Dept.
评估包装变更带来的市场影响性
Evaluate the impact on the market caused by the change of packaging material or label
3.8 安全环保部/EHS Department
评估安全隐患和废弃物带来的环境污染的影响性
Evaluate the potential safety risk and impact on the environment caused by wastage resulting from change
3.9 生产运营部/Production Department
评估对产品的工艺规程和生产计划的影响
Evaluate the impact of the change on the process instruction and production plan
3.10 质量控制部/Quality Control
●评估变更后的检验方法、质量标准的适用性
Evaluate the suitability of analytical test methods and specification if the change is implemented
●评估是否需要附加的试验
Evaluate whether need additional experiment or not
3.11 质量管理部/Quality Management
●发放变更编号Issue an official number for the change
●评估对验证状态的影响，决定是否需要验证
Evaluate the impact on the validation status and determine whether validation is required or not
●评估对产品质量的潜在影响
Evaluate the potential impact on the product quality
●评估变更对地方药监局和客户的影响
Evaluate the impact on the local authorities or local customers
●对变更进行分级Classify the changes
●决定是否对变更进行风险评估
Determine whether there is a need to perform a risk assessment for the proposed change
●审核质量风险评估Review quality risk assessment
●保证变更流程符合此规程
Ensure that the process of change is in compliance with this procedure
●批准/拒绝变更Approve/Reject the change
3.12 质量负责人/Head of Quality
批准/拒绝关键变更
Approve/Reject the critical change
4 定义/Definition
4.1 关键变更：对中间体或产品有潜在重大质量风险的变更。通常需要进行生产试验、确认、验证及必要的质量研究。关键变更包括但不仅限于：
Critical changes: Refer to changes that have significant potential quality risk on the intermediate or the product. A production trial, qualification, validation or necessary quality studies will be required for this type of change. Critical changes include but are not limited to:
●改变工艺路线或者关键工艺参数
Change of process route or critical process parameters
●工艺中引入新的溶媒、溶剂、物料Addition of new solvents and materials
●改变关键的中间控制参数Change of key in process control parameters
●改变起始物料、中间体或者成品质量标准的限度
Change in specification for starting materials, intermediates or finished products
●改变分析方法Change of analytical methods
●生产及质量管理用计算机系统变更
Change of computerized system used in production & quality management
●改变灭菌工艺Modification of sterilization process
●改变发酵用生产菌种（指主细胞库）
Modification of strain used in fermentation process (i.e. master cell bank)
●变更药品生产场地Change of manufacturing site
●关键设备的变更Change of key equipment
●重要公用系统（如水系统、空调系统等）的变更
Change of critical utilities (e.g. water system, HVAC system)
●内包装材料材质的变更Change of primary packaging materials
●变更药品处方中辅料品种或调整用量
Change of excipient or its quantities in the manufacturing formula
4.2 重大变更：对产品质量、性能可能产生较大风险的变更。依据评估结果决定是否进行验证或质量研究。重大变更包括但不仅限于：
Major Changes: Refer to changes that may have major risk on product quality and property. The determination of requirement of validation or quality study will be based on the evaluation result. Major changes include but not are limited to:
●同类型/型号的关键设备的更新
Replacement of key equipment with the same type
●产品包装形式的变更，包括标签、瓦楞纸箱等的变更
Change of packaging specification (change of label and cartons, etc.)
●变更法规中没有明确规定的分析方法
Change of non-compendial analytical method
●设备清洁程序的变更Change of cleaning method
●重要公用系统（如水系统、空调系统）的维修
Repair of critical utilities system (e.g. water system, HVAC system)
4.3 微小变更：对中间体或产品质量没有影响或者有潜在较小影响的变更。通常不进行验证、必要时可以采用同期验证的方法。微小变更包括但不仅限于：
Minor Changes: Refer to changes that have no or minor impact on the quality of the intermediate or the product. Validation is not required for this type of change. However, concurrent validation may be needed when necessary. Minor changes include but are not limited to:
●对中间体和产品质量没有影响的非关键生产工艺参数的变更
Change of non-critical process parameters which have no impact on the quality of intermediates and finished products
●外包装材料材质的变更Change of secondary packaging material
●包装材料规格尺寸的变更Change in dimension of packaging material
●产品包装装量的变更Change of quantities packed
●同类型/型号的非关键设备的更新
Replacement of non-critical equipment with the same type
4.4 IPC：中间工艺控制In-Process Control
5 程序/Procedure
变更控制流程图参加附录1
The flow chart for Change Control procedure is indicated in Appendix 1.
5.1 变更申请人填写《变更控制表》，完成章节A中的内容
The applicant of change raises a “Change Control Form” and completes section A with the following information:
a) 变更名称Name of Change
b) 变更类别Type of Change
c) 变更描述，包括变更方案
Description of the change, including the plan of change
d) 变更原因/理由Reason/Justification of the change
e) 偏差或纠正预防行动的相关编号（如有）Related deviation or CAPA NO.(if any)
f) 受影响文件的文件名称和文件编号
Document title and document number of all affected documents
5.2 质量管理部变更管理员接收到变更控制表章节A内容后，完成下述内容：
After receiving the Change Control form, QM Change Control Officer should complete the following:
a) 在《变更登记台帐》上对变更进行登记，按评估需求打印变更控制表，并按照以下
原则发放变更编号：
Register the change on the “Change Log Sheet” and according to the needs assessment print the “Change Control Form” and issue the change number according to the numbering procedure below:
CHTT-UYYAA
TT：工厂代号由两位数字组成，详见《文件编号规程》
Plant code consists of two digits as detailed in “Document Numbering”
U：部门或车间代码由一位字母或车间代号组成，分列如下：
Department or workshop code which consists of one letter or workshop number as below:
YY：年，后2位。The last two digits of year
AAA：年度顺序号，由三位数组成，从001开始。
Three digit sequential number starting from 001 every year
b) 根据质量风险管理规程》决定是否进行风险评估。若需要编写风险评估报告，通知
变更申请人编写；否则由变更申请人填写风险评估简述。
Determine whether to perform the risk assessment using the “Quality Risk Management”. If necessary, inform the applicant of change to generate a risk assessment report. Otherwise, the applicant of change shall complete the brief risk assessment part.
c) 根据变更类别及附录2《变更评估部门表》，确定参与评估的部门，并据此打印适用
的变更控制表，如果变更的内容可能会引起歧义，可决定组织变更评估小组成员（包括主题专家）进行会议评估。
Determine which department is to evaluate the change depending on the type of change, and Appendix 2 “Department to Evaluate the Changes Proposed ” , and then print the applicable record. Where there may be dissidence encountered, a meeting should be organized in which all department leads and subject matter exports (if necessary) shall participate.
5.3 所有相关部门进行变更评估，并完成章节D。
All associated departments shall perform the evaluation and complete section D.
5.4 驻厂质量经理对变更进行分级，完成章节F。
The plant Quality Manager shall classify the changes and complete section E.
5.5 变更批准Approval of Change
5.5.1微小变更由驻厂质量经理批准。
Minor changes shall be approved by the plant Quality Manager.
5.5.2重大变更由质量管理部部长批准。
Major changes shall be approved by the QM director.
5.5.3关键变更由公司质量负责人批准。
Critical changes shall be approved by the company Head of Quality.
5.5.4如果变更未得到批准，变更申请结束，变更控制表由质量管理部变更管理员存档。If a proposed change is rejected, it shall be cancelled and the Change Control form raised shall be submitted to QM Change Control Officer for arhival.
5.6 变更批准后，变更申请部门协调实施行动，完成后，填写章节G并附上所有的实施支持文件。
After approval of a change, the department requesting the change will coordinate to implement the change and complete section G with supporting documents upon completion.
5.7 所有相关部门进行变更实施结果审核，并完成章节H，如有意见，变更申请部门进行改进，直至满意。
All associated departments shall review the change results after implementation and complete section H. Any comments raised by the reviewing department shall be solved satisfactorily by the department requesting the change.
5.8 批准变更关闭Closure of Change
变更实施批准人对变更结果进行最后审核，如结果满意，则批准关闭，否则，变更申请部门需要进行改进，直至批准。
The approver who approves the change to proceed shall perform the final review and approve for closure if satisfied with the results. Otherwise, the department requesting the change shall take necessary actions until the change gets approved.
5.9 文件保管/Archival of Document
5.9.1所有的变更记录由质量管理部变更管理员进行保管。
All change records shall be filed by the QM Change Control Officer.
5.9.2质量管理部变更管理员每季度最后一个月末进行一次汇总，向质量负责人汇报，如果没有按时完成的变更，需要说明延迟或取消的原因。
The change summary shall be prepared by QM change Control Officer at the end of each quarter and submitted to the head of Quality. The reasons for delay or cancellation(if any)shall be included for those changes which are not completed as per
plan.
5.9.3每年在产品年度回顾中对年度发生的变更进行汇总分析。
All changes encountered in a year shall be summarized and analyzed in the Annual Product Review.
6 参考资料及相关SOP/References and Related SOPs.
6.1 中华人民共和国药品生产质量管理规范（2010年修订）
The People’s Republic of China Good Manufacturing Practice – Medicinal Products (Revision 2010)
6.2 欧盟药品管理通则第4卷– 欧盟人用/兽用药品生产质量管理规范
EudrsLexthe Rules Governing Medicinal Products in the European Union, Volume 4 EU Guidelines to Good Manufacturing Practice – Medicinal Products for Human and Veterinary Use.
6.3 文件编号规程Document Numbering
6.4 文件管理规程Document Management
6.5 供应商评估与选择管理规程Supplier Evaluation and Selection
6.6 产品包装设计、印刷管理规程
Management of Packaging Material Design & Printing
6.7 质量风险管理规程Quality Risk Management
7 附录/Appendices
7.1 附录1规程流程图
Appendix 1Flow Chart of Procedure
7.2 附录2变更评估部门表
Appendix 2Department to Evaluate the Changes Proposed
8 附件/Attachment
无None
9 记录/Records
9.1 变更控制表Change Control Form
9.2 变更登记台帐Change Log Sheet
10 颁发部门、分发部门/Issuing Department and Distribution Department
10.1 颁发部门Issuing Department：质量管理部QM
10.2 分发部门Distribution Department：
质量管理部QM、质量控制部QC、生产运营部Production、公共支持部Utility、物流部Logistic、安全环保部EHS、综合管理部Administration、研发中心R&D、销售中心Sales Center、销售部Sales Dept.、各工厂All plants和各生产车间All workshops.
11 培训要求/Training requirements
培训对象Trainee：全体员工All employees。
12 修订历史/History of Revisions
附录Appendix 1
（第1页共1页）
规程流程图
Flow Chart of Procedure
申请人Applicant of Change 质量管理部变更管理员
QM Change Control
Officer
评估部门
Evaluation Dept.
批准人
Approver
App
endi
x 2
（第
1页
共1
页）
变更
评估
部门
表
Dep
artm
ent
to
Eval
uate
the
Cha
nge
s
Pro
pos
ed