3_变更控制管理规程

变更控制管理规程Change Control Management1 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/Scope2.1 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 Site2.2 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 “SupplierEvaluation 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/Responsibilities3.1 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 schedule3.2 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 documentation3.3 国际部/International Dept.a) 评估对国外客户的影响Evaluate the impact on foreign customersb) 评估对国外注册资料的影响Evaluate the impact on the foreign registrationfile3.4 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 documentation3.5 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 applicable3.6 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 documentation3.7 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 label3.8 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 change3.9 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 plan3.10 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 not3.11 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 change3.12 质量负责人/Head of Quality批准/拒绝关键变更Approve/Reject the critical change4 定义/Definition4.1 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 formula4.2 重大变更：对产品质量、性能可能产生较大风险的变更。