山东2008年验证总计划--山东瑞博德制药有限公司

TRIPARDUS VALIDATION MASTER PLAN/瑞博德验证主计划

压缩机、除湿装置、除水装置、去杂装置、加热装置、后道过滤器的配置、终端过滤器及管道连接、电气等公用介质的连接。

——Carry out the pressure test to confirm that the leakage rate meets the specifications. 进行压力实验，确认泄漏率符合标准。

——Collect the information on equipments, filters and pips including the material report of critical parts, integrity report of filters and operation manual, and write the SOP.

收集各设备、过滤器、管道等证明材料，包括关键部位的材质报告、过滤器的完好性报告、操作手册，草拟SOP。 7.6.3 Operational Qualification/运行确认

Carry out the empty run for each piece of equipment according to the drafted SOP to test that whether the machine can operate in the specified range and meet the technical specifications. The tested items include the pressure, exhausting temperature, current, voltage, etc. 根据草拟的标准操作规程对设备的每一部分及整体进行足够的空载试验，证明该机是否能在要求范围内准确运行并达到规定的技术指标。运行测试项目有压缩机的压力、排温、电流、电压、产气能力。

7.6.4 Performance Qualification/性能确认

Test the outlet air quality during the normal operation to evaluate whether the air meet the process requirements. The tested items include waters, oil, air particles, microbes, etc. 压缩空气系统正常运行后，通过检测空气出口的质量评价是否符合工艺及产品的需要。主要检测项目有：水分、油分、尘埃粒子、微生物等指标。

7.7

Instruments and equipments validations/仪器设备验证

Including production equipments, test instruments, public supporting equipments 包括生产设备、检验设备、公用支持设备 7.7.1 Design Qualification/设计确认

Check whether the suppliers and design documentation including the drawings conform to URS and GMP requirements before the purchase. 在仪器设备购买前审核设备设计文件（包括图纸）、供应商等是否符合用户需求标准和GMP要求。

——Approval of suppliers: the supplier’s operational conditions and ability of delivery in time; training and technical support for installation, use and maintenance; manufacturing experiences of the equipments including the customers range, years of production, capacity, GMP familiarity; availability of field test.

供应商的选择情况：供应商的运营情况是否能保证及时供货；对安装使用及将来维修保养能提供的培训和技术支持能力；此类设备的生产经验，包括用户范围、生产年限、数量、GMP知识熟悉的程度；能否在供应商所在地进行现场测试。

——Documentation check: design drawings, test and review documents; bill of materials, components, instruments, material acceptance report; equipment parts, utility and standardization of measuring devices; suggested equipments and spare parts list; suggested lubricants list; supplied operation, cleaning, maintenance procedures as well as special requirements, such as the safety and protection cautions.

审查文件材料：设计制造图纸；工厂的测试和检查文件；材料清单、部件清单、仪器仪表清单、材料验收报告；设备的零件、计量仪表的通用性和标准化程度；建议的备品备件清单；推荐的润滑剂清单；推荐的运行、清洗、维护、保养程序并包括特殊要

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求如安全保护措施要求。

——FAT test: suppliers will be required to carry out the FAT test when necessary. 现场测试（FAT）：必要时，可以安排到供应商现场进行测试。 7.7.2 Installation Qualification/安装确认

Check the technical information from the supplier, equipments, spare parts and installation, to confirm whether they meet the DQ requirements

对供应商提供的技术资料的核查，对设备、备品备件检查及验收，以及设备的安装检查，以确认是否符合DQ的要求。

——Archive of technical information: check the effectiveness and accuracy of drawings, equipments list, certificates, instructions and operation manual from the suppliers. The supplier will be asked to supply any information that is found incomplete or with error during the installation.

技术资料的检查归档: 是指资料档案化管理工作。由有关人员检查审核供应商提供的图纸、设备清单、各类证书、说明书或操作手册的有效性和准确性。在安装确认过程中如发现供应商提供的资料有差错或不完善，应及时向供应商索取。 ——Acceptance testing of spare parts:

Acceptance testing of spare parts: the spare parts will be checked by referring to the supplier’s list and then warehoused. The warehoused spare parts should be recorded according to the equipments management requirements. 备品备件验收: 由备件验收人按照供应商提供的备品备件清单，检查实物，将实物验收入库。入库备件应按设备管理要求，做好台帐。

——Installation check and acceptance: the installation should be checked according to the process flow chart, installation drawings and recorded. The installation should conform to the design specifications. 安装的检查及验收: 由专人根据工艺流程、安装图检查设备实际安装情况，并做好安装检查记录，安装结果应符合安装设计要求。

——Evaluation and approval of IQ: the evaluation and approval or rejected conclusions should be made after the completion of installation. 安装确认的评价和批准: 设备安装确认结束后，应有专人做出评价，并做出是否合格的结论。 ——Draft the SOP. 草拟SOP。

7.7.3 Operational Qualification/运行确认

The OQ refers to the test run of individual equipment or system according to the drafted SOP; it is a series of activities to prove that the technical parameters of equipments or system conform to the specified requirements.

运行确认系指通过按草拟的标准操作规程（SOP）进行单机或系统运行试验。运行确认是证明设备或系统各项技术参数能否达到设定要求的一系列活动。

——Calibration of measuring instruments: check whether the instruments are calibrated and labeled with corresponding identity.

计量器具的校准： 检查设备上的仪器仪表是否检定/校准，并有相应的标志，如果没有则按要求进行检定和校准。

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——Function test: check the equipment function and safety by referring to the established specifications and technical information, such as the inter-lock, emergency stoop, surface anti-slip, working conditions that are hazardous to health and noise, make sure they all meet the specified standards.

功能测试：按照确定的标准以及设备技术资料说明书所列标准，检查设备的每项功能及安全性，如内部锁定、紧急制动键、表面防滑、有碍健康的工作条件及噪音，确证其符合标准。

——SOP training: the relevant SOPs of operation, cleaning, maintenance should be established during the OQ, and the training and assessment should be carried out for the operators and engineers.

操作规程培训：设备运行确认中应制订相应的操作规程、清洗规程、维护保养规程，并对设备的操作及维修人员进行培训和考核。

——Evaluation and approval of OQ the evaluation and approval or rejected conclusions should be made after the completion of installation.

运行确认的评价和批准：设备运行确认结束后，应有专人做出评价，并做出是否合格的结论。

7.7.4 Performance Qualification/性能确认

It is the systematic check and test that the equipments and system meet the design specifications and GMP requirements. The PQ can be carried out according to the equipments actual conditions, with OQ or Process Validation simultaneously. 证明设备、系统是否达到设计标准和GMP有关规范要求而进行的系统性检查和试验，本部分可根据设备的具体情况进行，某些设备可以将运行和性能一起确认，某些设备可以将性能确认与工艺验证一起。

——Production simulation or load run: the operation conditions can be designed according to the product characteristics, with empty run or load run. Test the reliability and stability of running parameters of equipments in empty run, and confirm whether the equipments meet the process requirements by referring to the test results. 模拟生产状态或有负荷状态下的运行状况： 应根据产品的特点设计工艺运行条件，可用空白物料或产品进行测试。在负载运行中考察设备运行的可靠性、运行参数的稳定性，并通过产品进行测试的结果确证设备是否符合生产工艺要求。

——Three batches should be simulated at least to prove the reproducibility of running results. 为了证实运行结果具有重现性，模拟生产至少三批。

——Evaluation and approval of PQ the evaluation and approval or rejected conclusions should be made after the completion of installation.

性能确认的评价和批准：设备性能确认结束后，应有专人作出评价，并作出是否合格的结论。

7.8

Equipment cleaning validation/设备清洁验证

Cleaning validation is to testify that the residues (visible an invisible, including the reagent residue or residue from last product) meet the cleaning limit requirements, and will not bring the cross-contamination. Three batches will be validated generally. The confirmation of chemical residue and process validation can be conducted simultaneously.

是证明经过清洁程序清洁后，设备上残留物（可见的和不可见的：包括前一产品的残留物或清洗过程中洗涤剂的残留物）达到了规定的清洁限度要求，不会对将生产的产品造成交叉污染。清洁验证一般为三个生产批次，活性物质的化学残留量确认可以与工艺验证同时

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进行。

7.8.1 Establishment of cleaning procedure/建立清洁规程

The cleaning procedure should be established prior to the validation according to the product and equipment characteristics, process requirements. The training should be carried out for the cleaners.

在清洁验证之前应根据产品的性质、设备特点、生产工艺等因素拟定清洁方法并制定清洁规程，对清洁人员进行培训。

7.8.2 Evaluation of effectiveness and risk assessment for cleaning procedure

对待验证的清洗程序的有效性、风险性进行评估

——Clean the reference according to the product characteristics. The hardest cleaning substance or most active substance will be chosen as the reference. Consideration should be made for the residue if the cleaning or disinfection agent is used.

应根据生产设备所生产的产品性质清洁验证的参照物制。参照物的选定依据为应是用该清洗程序所清洗得所有物质中最难清洁的物质或活性最强的物质。若清洗程序中选用了清洁剂或消毒剂，应考虑清洁剂和消毒剂的残留。

——The hardest cleaning parts should be determined according to the equipments and cleaning procedure. The sampling points are generally the equipment dead leg, inaccessible part for cleaning agent, such as the branch pipe, Y-type pipe, places with diameters becoming large, and non-smooth parts in the internal surface. 应根据设备和清洁程序确定最难清洁的部位，作为取样点，一般为设备的死角、清洁剂不易接触部位、支管、岔管处、管径由小变大处、内表面不光滑处等应为最难清洁部位。

7.8.3 Validation of sampling method/验证取样方法

Suitable sampling method should be adopted according to equipment structure and cleaning method, including the swab sampling and rinsing sampling. The sampling method must be validated prior to the cleaning validation to testify the suitability of cleaning method and dissolution process. The sampling recovery test will be carried out in the sampling method validation, and the obtained recovery rate will be cited in the final calculation. 应根据设备的清洁方法和结构特点，合理的选择取样方法，取样方法一般包括擦拭取样和淋洗水取样。在设备的清洁验证前，应对取样方法进行验证，以证实方法及所选用的溶剂、取样人员操作、残留物转移到药签或淋水中、样品的溶出过程的适用性，取样方法的验证一般为取样回收率试验，将测得的取样回收率代入到最终的验证计算中。

7.8.4 Confirmation of Chemical Residue/确定化学残留量

The hardest cleaning substance with largest batch size will be manufactured before the product-change, and the product with smallest batch size will be manufactured after the product-change. The permitted residue carryover of a product into the next product will be 1/1000th of the minimum daily dose (or 10ppm) of the former product

以确定的最难清洗物质的最大批量作为换线前生产产品，所有生产产品中的最小批量的产品作为换线后产品，换线前的活性物质在换线后产品中的残留量不超过该物质日服用剂量的1/1000或换线后产品单位剂量中所含残留不超过10PPM。 7.8.5 Confirmation of microbes residue/确定微生物残留量

The products manufactured in Tripardus are non-sterile products, and the cleaning results should not be more than the microbes limits of worst case product.

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