产品技术转移.doc

精品文档Product Technical Transfer产品技术转移1Objective 目的This procedure defines the procedure for the product technical transfer from the transferor to transferee. Make sure the technical transfer follows a standard procedure, to ensure that products are produced and stored according to appropriate documentation in order to obtain the required quality.本规程规定了产品技术由转出方转移到接收方的标准操作流程，使产品引入过程规范地运作，有效地评估和控制新产品引入的风险，找出产品工艺和质量控制的关键控制点，确保产品能顺利稳定地转移至生产线进行投产，稳定高效地生产出符合产品质量标准的产品。2Scope范围This SOP applies to the technical transfer of all the products from different resources including research institutes and companies cooperation with SLP.本规程适用于所有来源的产品，包括由研发机构或其它公司向生产线技术转移的所有产品。3Responsibilities 职责3.1TD is responsible for drafting, reviewing, revising, training and implementing this SOP.技术部负责本规程的起草、审核、修订、培训和执行。3.2QA, QC, production, logistic department is responsible for reviewing and supervising the implementation of this procedure.QA、QC、生产及物控部门负责审核并监督本规程的执行 。3.3Quality director is responsible for approving this procedure.质量总监负责本规程的批准。3.4Technical transfer staff should understand and implement this procedure.技术转移相关人员理解并执行本规程。4Definitions 定义4.1Technical transferor refers to the original manufacture or institutes who keep the technical data.技术转出方是指持有产品技术资料的原生产商或研究单位。4.2Technical transferee refers to the team that consist of TD, PD, QC, QA, etc.技术接收方是指由技术部、生产部、QC部、QA部等部门成员组成的项目组。5Procedures 程序5.1Classification by product source 产品来源分类5.1.1Domestic contract processing product 国内委托加工产品Domestic contract processing refers to the processing producing products basing on the drug regulations of China and the target market will be the Chinese mainland. 国内委托加工是指协助国内企业按照中国法规要求生产且最终产品在中国境内上市销售的产品。5.1.2Overseas contract processing product境外委托加工产品Overseas contract processing refers to contract processing producing products basing on EP, USP, JP, BP ect. and the target market will be the overseas.境外代加工是指协助其它企业按照国外法规要求生产且最终产品在境外上市销售的产品。5.1.3Registry product 公司注册产品Other companies or institutes transfer their technical achievement, technology and information to our company by various means, and we will have the all or part of the ownership of the product. For example, ANDA, NDA and new product which will be declared in domestic.外部企业或研究单位通过各种方式将科学技术成果、技术、信息转让给我公司，最终我公司拥有该技术的全部或部分所有权的产品，如ANDA、NDA、国内新药申报产品等。 5.2Procedure of product technical transfer产品技术转移程序5.2.1Establish the project of product technical transfer 建立产品技术转移项目5.2.1.1Confirm the development status of process and analytical methods of transfer project.确定产品技术转移项目的产品的处方和工艺研发的状态。5.2.1.2Designate the responsible person of the transferor and the transferee, establish technical transfer team.确定转出方和接收方项目负责人，组建技术转移小组。5.2.1.3The transferee team review the technical documents referred by transferor, according to . Sign on to confirm they comply with requirement. Copy or scan reference documents used in test methods transfer.技术转移小组审核技术转出方提交的转移资料，审核工作参见通用产品技术转移检查表。核对文件清单，确认符合要求和法规规定后在技术转移记录上签字确认。相关文件复印一份或扫描一份用于分析方法转移工作。5.2.2Risk assessment and change control of the product technical transfer 转入产品技术转移风险评估和变更控制5.2.2.1Risk assessment should follow as the two ways:新产品引入的风险评估分为下列两个方面进行：l TD manager should organize the risk assessment regarding to the interaction from the new product and current products .Assess the affect to current materials, premises, facilities, equipments, personnel, documentation, regulations, production, lab control, packaging, labeling. Identify the feasibility of the transfer and the following work. Refer to .技术部经理应组织对引入的新产品可能对现有生产线的物料、厂房、设施、设备、人员、文件、法规、生产、实验室控制、包装与标签等相关方面产生的影响和生产线现有产品对新引入产品的影响进行风险评估，确定转移的可行性和需要开展的工作。参见新产品引入风险分析表。l Project manager should organize the risk assessment of the process and quality control for the new product. Identify the optimization and validation activities against the problems and potential risks. Refer to .项目负责人应组织质量研究和工艺研究人员对引入的新产品的工艺研究和质量研究的情况进行风险分析，针对存在的问题和风险制订相应的优化措施和验证措施。参见新产品工艺和质量风险分析表。5.2.2.2Change control变更控制A new product transfer into plant is in the range of change control, Basing on the result of risk assessment, supervise the process according to the manage procedure of if the project is feasible, take correspondence measures combine with the product transfer protocol, avoid the influence between original products and the new introduced product.在生产线上引入新的产品属于变更控制范围，基于风险评估的结果，对于可执行的项目根据变更控制管理程序进行过程的监控，与产品转移方案相结合采取相应措施，避免原有产品和新引入的产品的相互影响。5.2.3Prepare technical transfer plan编写技术转移计划5.2.3.1Write technical transfer plan according to the process flow and the companys technical transfer strategy.根据新引入产品的工艺流程和公司技术转移策略等编写技术转移计划。5.2.3.2Technical transfer protocol and technical transfer list should be written by personnel assigned by the responsible person from the transferee. And it should be approved by the quality director.技术转移计划由接收方项目负责人指定专人编写，经转移小组审核后由质量总监批准。5.2.3.3The transferees responsible person should organize the maintenance and amendment of the technical transfer plan.技术转移计划由接收方负责人负责组织进行维护和修订。5.2.4The transferees responsible person should organize drafting the product validation master plan and make it a guide to the validation work when a new product is introduced. Make sure the introduction process is effectively controlled and verified. 接收方负责人负责组织编写产品验证主计划，为新产品的引入所产生的验证工作提供文件指导和规划，保证产品引入过程中相关工作得到有效的控制和确认。5.2.4.1Numbering of the product validation master plan: PVMP-Project code-Serial No., refer to . 产品验证主计划的编号原则：PVMP项目编号版本号，参见验证的组织和实施。5.2.4.2Product validation master plan should include but not limited to:l Product introduction and product-related validation plan introductionl Responsibilities of relevant departments l Acceptance criteria of the process development, analytical development and cleaning residue at different stages of the product transferl Validation list of relevant equipment, utilities and facilitiesl Validation list of the method validation, cleaning validation, process validation and packaging validation.l Validation documentation list产品验证主计划应该包括但是不限于下列内容：l 产品概述和产品相关验证的总体计划简介。l 产品引入相关部门的职责和分工。l 从产品转移开始各阶段的工艺研究、质量研究和清洁残留的接受标准。l 引入产品相关的设备、设施和公用系统的验证清单。l 引入产品的分析方法验证、清洁验证、工艺验证和包装验证清单。l 相关验证文件列表。5.2.5Analytical test methods transfer 分析方法转移5.2.5.1Establish a quality development team who is responsible for the analytical method transfer. Assign responsibilities for the team leader and every team member. 成立负责分析方法转移工作的质量研究小组，确定项目质量研究负责人，明确项目组成员工作职责分工。5.2.5.2Quality development team implements the analytical method transfer according to technical transfer plan and SOP .质量研究小组根据技术转移项目计划和标准操作程序分析方法转移的要求执行分析方法转移工作。5.2.5.3Quality development team leader should draft an analytical method transfer plan as well as an analytical method training plan. The analytical method training plan should include the explaining and site operation. Quality development team leader organize the training of the analysts and QA personnel, to ensure that trainees understand the procedures correctly, and implement the key points of the new method in an accurate way.项目质量研究负责人在制定分析方法转移计划的同时应制定分析方法培训计划，包括新产品分析方法讲析和实际操作两个方面。对负责转移和接受分析方法操作的QC分析人员和相关QA人员进行有效的培训，确保相关分析人员能正确理解分析程序，准确无误地执行新产品分析方法的操作要领。5.2.6Pharmaceutical technology transfer 工艺技术转移5.2.6.1Establish a process development team who is responsible for the product process transfer. Assign responsibilities for the team leader and every team member.成立负责工艺技术转移工作的项目工艺研究小组，确定项目工艺研究负责人，明确项目组成员工作职责分工。5.2.6.2Process development team leader organize the reviewing of the product formulation and process documents provided by the transferor, including:l Feasibility of the processl Rationale of the quality specificationl Current production capacity against the production demand项目工艺研究负责人组织相关人员对产品转出方提供的产品处方和工艺资料进行审核：l 产品工艺的可行性。l 质量标准设置的合理性。l 公司现有生产工艺条件是否满足产品生产需求。5.2.6.3Process development team leader should discuss the problems discovered and questions with the transferor, and confirm the solutions.项目工艺研究负责人将发现的问题或存在的疑问与产品转出方相关人员进行讨论，确认问题的处理措施。5.2.6.4Process development team leader organize the team to draft a process technical transfer protocol basing on the risk assessment results. The format of the protocol refers to the process technical transfer protocol template. Process technical transfer protocol should be drafted according to the technical transfer agreement, could include but not limited to:l List of the required material, equipment, instrument and spare partsl List of the process development Triall Evaluation of cleaning method for chemical residue l Product process transfer plan项目工艺研究负责人根据风险分析的结果，组织项目工艺研究小组起草工艺技术转移方案，文件格式参照工艺技术转移方案的模版。工艺技术转移方案内容可以根据合作协议的要求编写，可以参考但不仅限于下列内容：l 新引入的产品所需的物料、设备、仪器和耗材清单l 工艺研究实验清单l 化学残留清洁方法评估l 工艺技术转移工作计划5.2.6.5Process development team leader should draft a technology transfer plan as well as a technology training plan. The technology training plan should include the explaining and site operation. Process development team leader organize the training of production operator and QA personnel, to ensure that trainees could to understand the procedures correctly, and implement the key points of the new process in an accurate way. 项目工艺研究负责人在制定工艺技术转移计划的同时应制定工艺技术培训计划，包括新产品工艺技术的讲析和实际操作两个方面。对负责转移和接受工艺技术操作的生产一线人员和生产现场QA人员进行有效的培训，确保相关人员能正确理解工艺步骤，熟悉新产品的关键工艺参数和关键控制点，准确无误地执行新产品工艺技术的操作要领。5.2.6.6Process development team submits requests for required materials, equipments, instruments and spare parts according to the approved process technical transfer protocol.项目工艺研究组按照批准的工艺技术转移方案，申请采购需要补充的物料、设备、仪器和耗材。5.2.6.7Process development team performs formulation and process feasibility trial according to approved process development protocol, and prepares process feasibility trial reports 项目工艺研究组按照批准的工艺研究方案对产品处方和工艺适应性进行确认，编写相应的工艺适应性研究报告。5.2.6.8After process feasibility trial, the project team prepares process optimization, process scale-up and process qualification protocol basing on the critical quality attributes and process design requirements, then implement to investigate and determine the critical process parameters and equipment operation parameters. Refer to , , .工艺适应性研究结束，项目组根据产品的关键质量属性和工艺设计要求，编写工艺优化、工艺放大和工艺确认方案，进行产品工艺优化、工艺放大和工艺确认工作，考察和确定关键工艺参数和设备运行参数。参见工艺优化、工艺放大和工艺确认。5.2.6.9After the process qualification batch, if the quality control items are comply with quality specifications, critical process parameters and equipment operation parameters are consistent, and the report of the process qualification batch is approved, then the process technical transfer is completed. The transferred product could be put into production of process performance qualification batches.工艺确认批生产结束，若产品的各项质量控制项目均符合质量标准，关键工艺控制参数和设备运行参数稳定，工艺确认批生产报告批准后，转移产品可以进入工艺性能确认阶段。5.2.6.10Production manager organize relevant personnel to establish a process validation team to execute process performance qualification. Refer to .生产经理组织相关人员成立验证小组组织实施产品的工艺性能确认，参见工艺验证。5.2.7Cleaning method development and verification产品清洁方法开发和确认5.2.7.1Newly introduced product will have an impact on the validation status of cleaning method for existing products. Process development team should calculate the maximum acceptable residue level of each active ingredient on unit area of common equipment and check solubility in the detergent of newly introduced active ingredient. 新产品的引入将会对生产线原有产品的清洁方法验证状态产生影响， 项目工艺研究组应计算新引入产品与其它现有产品共用设备上单位面积表面允许的所有活性成份的最大允许残留限度值，并确认新产品的活性成份在现用清洁溶剂中的溶解度。5.2.7.2Analytical development team should prepare the assay method and validation protocol according to the content of the active ingredient, and verify the chemical residue testing method.项目质量研究组参考新产品活性成份含量检测方法开发和编写确认方案，对新产品活性成份的化学残留检测方法进行确认。5.2.7.3Compare the maximum acceptable residue level and solubility in the detergent of the active ingredients in the newly introduced products and existing products. Based on the comparison, three different measures are as follow:综合比较生产线现有产品和新产品处方中活性成份的最大允许残留限度值和活性成份在现用清洁溶剂中的溶解度。根据比较结果可以分下列三种情况处理：l Class I: if the maximum acceptable residue level or solubility in the current detergent of the active ingredient in the newly introduced product is lower than that of the existing products, or there is ingredient in the product formula difficult to clean, the efficiency of the cleaning method should be verified using the equipment in pilot plant.I类：若新产品活性成份的最大允许残留限度值或在现用清洁溶剂中的溶解度最低，或者新产品处方成份中有难以清洁的成份，应在中试车间的工艺设备对清洁方法的清洁效果进行确认。l Class II: if the maximum acceptable residue level and solubility in the current detergent of the active ingredient in the newly introduced product is higher than that of the existing products, the efficiency of the cleaning method is not necessary to be verified using the equipment in pilot plant.II类：若新产品活性成份的最大允许残留限度值和在现用清洁溶剂中的溶解度比现有产品的都大，则不需要在中试车间的工艺设备上对清洁方法的清洁效果进行确认。l Class III: if the maximum acceptable residue level of current products will have negative impact on the newly introduced product, a revised maximum acceptable residue level should be established for current products and perform re-validation.III类：如果现有产品活性成份的最大允许残留限度值不符合新产品要求，应对现有产品进行限度修订和清洁再验证。5.2.7.4l For the Class I product, if current cleaning method has been verified on the pilot plant equipment and the result shows that it is suitable for the new product , then , the scale-up production as well as the cleaning validation can be enforced on the commercial production line . 对于I类中经中试车间工艺设备确认采用现有清洁方可以清洁干净的产品， 新产品可以正式转入生产线进行放大生产，同时进行清洁验证。l For Class I product for which current cleaning method could not be verified using pilot plant equipment, a new cleaning method should be developed and verified using pilot plant equipment before scale-up in production plant. After verification, scale-up production and cleaning validation in the commercial production line could be started. 对于I类中经中试车间工艺设备确认采用生产线现有清洁方法难以清洁干净的产品，应开发针对该产品的清洁方法，并应在进入生产线进行放大生产前，在中试车间对新开发清洁方法的清洁效果进行确认。确认合格后，新产品可以正式转入生产线进行放大生产，同时进行清洁验证。l For Class II product, the efficiency of cleaning method should be further verified during scale-up production. Cleaning validation report should be approved by Quality Director, that indicates the introduction of new product will not have negative impact on the cleaning validation status of the production line.II类产品，在生产线进行放大批生产的同时，应对使用现有清洁方法的清洁效果进行确认，清洁确认报告经质量总监批准后，标志着新产品的引入不会影响生产线清洁方法的验证状态。5.2.7.5The procedures of establishment of residual limits, microbial acceptance criteria, detergent residual limits and sampling method should be referring to .关于残留物、微生物、清洁剂残留的可接受限度建立和取样方法等程序参见清洁验证。5.2.8Product technical transfer report产品技术转移报告When the transfer of test methods and pharmaceutical technology are finished, A technical transfer report should be drafted by personnel from transferee and reviewed by the transferor as well as the transferee. It should be approved by the quality director finally, that means the technical transfer successful. Refer to annex 2 Product Transfer Report Outline.分析方法和工艺技术转移成功完成之后，技术接收方负责编写技术转移报告，由技术转出和接收方负责人审核后交质量总监批准确认产品技术转移工作完毕。参见附录2产品转移报告提纲。5.3Management of project documents产品技术转移的项目文件管理All the documents generated during the technical transfer process should be numbered, archived and retrieved according to .The document administrator should check and sorting all the documents and make sure they are put away at the end of a work stage . 技术转移过程中产生的所有文件应按研发项目文件管理的要求分阶段进行整理，每一个工作结束，技术部文件管理人员应对文件整理工作进行检查，确认所有相关文件已经按照要求整理好。5.3.1Before the scale-up and process qualification batch, the protocol of scale-up and process qualification, analytical method standard operation procedures and product specification should be approved by the quality director. The copies of analytical method standard operation procedures and product specifications should be sent to QA and QC, the original should be archived in project document folder.产品进行工艺放大和工艺确认前，工艺放大（确认）方案、分析方法操作规程和质量标准草案应经过质量总监批准。分析方法操作规程和质量标准草案的复印件两份分别转移给QC和QA，原件存在产品转移项目文件夹内。5.3.2After process qualification, project team leader should organize the team members, production supervisor, QC supervisor and QA personnel to review the analytical method standard operation procedures and the specifications of API, excipients, intermediate products and finish product, identify problems and determine the corresponding measures.工艺确认结束后，产品转移项目负责人应召集项目组成员、生产主管、QC主管、QA等相关人员对新产品分析方法操作规程和原料、辅料、中间产品、成品的质量标准草案进行审核，找出文件中存在的问题确定修改方案。5.3.3Before the process performance qualification batches, QC and QA department should prepare the SOPs of analytical method and specifications according to the revised proposal and document format special for our company. .工艺验证批（生物批）生产前，QC和QA部门负责按照确定的修改方案和公司的文件格式要求起草商业生产用的产品分析方法标准操作规程和原料、辅料、中间产品、成品的质量标准。5.3.4Production manager organize relevant personnel to prepare master formula, batch processing record, batch packaging record, process validation protocol and other production standard operation procedures needed. 生产经理组织相关人员编写工艺规程、批生产记录、批包装记录、工艺性能确认方案或其他需要增加的生产标准操作规程。5.3.5When process performance qualification batches are finished, project t