瓶装线包装验证方案最终版.docx

BOTTLE PACKAGING LINE VALIDATION PROTOCOL OF CIPROFLOXACIN TABLES 250mg USP 环丙沙星片250mg瓶装线包装验证方案1.0 PURPOSE:目的To establish that the packaging process for Ciprofloxacin Tablets 250mg will meet the predetermined specifications and quality attributes consistently.保证异烟肼片100mg瓶装线的包装过程能够符合预定规范和质量品质。2.0 SCOPE:范围This protocol is applicable for Packaging validation of Ciprofloxacin Tablets 250mg at SHIJIAZHUANG YILING PHARMACEUTICAL Co., LTD.本方案适用于石家庄以岭药业有限公司环丙沙星片250mg瓶装线的包装验证。3.0 RESPONSIBILITIES OF VALIDATION TEAM:验证小组职责Certification Staff验证人员Responsible for preparation, issue of packaging validation protocol and execution of packaging validation.负责准备工作，编写与执行包装验证方案Equipment Manager设备部经理Responsible for check, check(review), approve packaging validation program and ensure verification scheme can achieve verify compliance with regulations standard负责核实、复核、批准包装验证方案，确保验证方案可以达到验证标准符合规定Head-Production Dept.生产部经理Responsible for verification of packaging validation protocol and to ensure operation of the packaging equipment & support systems in order to pack the product within its design limits /specifications/ requirement.负责核实包装验证方案，确保生产设备及维护系统运行生产的产品符合设计规格Head-Quality Control:QC经理Responsible for verification of packaging validation protocol and to ensure operation of lab activities to achieve optimum critical parameters负责核实包装验证方案，确保化验室的检验活动符合要求， 以确定和实现最佳关键参数Head-Quality Assurance:QA经理Review and approval plan, review the specific production processes comply with GMP regulations. Also responsible for result assessment, packing and packaging records of validation conclusions related to revise.复核与批准方案，审核具体生产流程符合GMP相关规定。同时负责结果评估，包装验证结论还有批包装记录相关修订。4.0 ACCEPTANCE CRITERIA:可接受标准All the product quality parameters must comply with the acceptance criteria as specified in this protocol consistently for three consecutive batches by optimizing the critical packaging parameters during the first batch.通过第一个批次确定关键包装参数及其范围，共进行三个连续批次，所有产品质量必须满足本方案确定的接受标准，通过第一个批次确定的合格的关键包装参数，共进行三个连续批次，所有产品质量必须满足本方案确定的标准5.0PROCEDURE:规程Execute three consecutive batches as per Batch Packaging Record. Record the critical parameters of the packaging unit operations as described in this protocol and compile subsequent test report. Optimize the critical parameters during validation of first batch and the optimized parameters to be verified in next two consecutive batches. Raise (Submit) Deviation Report as per YLS-SOP-QA002, if any abnormalities found during the entire packaging validation. If required(If necessary), Corrective actions and preventive actions to be taken as per SOP No.: YLS-SOP-QA033 before proceeding to next batch.根据批包装记录进行三个连续批次。记录本方案所描述的包装机的关键运行参数。在第一批次验证时找到最佳关键参数，应用在最后的两个连续批次当中。如在整个包装验证过程中出现任何异常，根据YLS-SOP-QA002提交偏差报告。如果必要，在下一批次进行前根据操作规程YLS-SOP-QA033进行纠正及相关预防措施。6.0 产品详细Brand Name:产品名称：Ciproflxacin Tablets 250mg环丙沙星片250mgB. Size:批量：150万片Shelf Life:有效期：Dosage Forms:剂型：片剂Generic Name仿制药名称：Ciproflxacin Tablets 250mg环丙沙星片250mgContract Giver：合同方：Ascend Laboratories LLC 阿森达Product Code:产品代码：FP00003Pack Size 包装规格：30片/瓶Label Claim:标签声明：Average weight:平均片重：185.0-215.0mg7.0REFERENCE DOCUMENTS FOR METHOD OF PACKAGINGAND TESTING:包裝与测试方法参考文件S/No序号NAME OF THE DOCUMENT文件名称Document Number文件编号1Picklist 包装指令PP*2Batch Packaging Record 批包装记录BPR-0153Product specifications and Test Procedure 产品标准和检验方法YLS-QS-FP003；YLS-QTM-FP0014 Test method of leakage test 密封试验测试方法YLS-QTM-GR095Note: All approved current version of relevant SOPs and documents must be referred.注: 必须列出所有涉及到的现行SOP和文件8.0 REASON FOR VALIDATION:验证原因Reasons原因Tick in the appropriate row在相应项目上划Commercial Manufacturing of pre-approved product 注册批准产品商业生产9.0 包装材料列表S. No.序号Item Code物料代码Name of the Packing Material包材名称Description描述Quantity数量Units单位1P00013120ml HDPE Bottle120ml HDPE瓶120ml2P00114120ml HDPE Bottle Cap120ml HDPE瓶盖17.15mm*43.80mm3P00041Shrinkfilm热收缩膜245mm18m4P00272Shipper 大箱338mm240mm220mm5P00067Shipper Cardboard 大箱垫板328mm230mm6L00003Pallet label货盘签NA7L00005Bottle Label异烟肼瓶签NA10.0 EQUIPMENT DETAILS:设备详细资料10.1 PACKAGING EQUIPMENT DETAILS:包装设备详细资料S. No.序号Packing Material Name包装设备名称Equipment ID设备编号Supplier供应商Description描述1PU-25FC high speed bottle unscramblePU-25FC高速理瓶机PBM-01Pharmapack Packaging equipment co., LTD珐玛珈（广州）包装设备有限公司Bottle unscramble理瓶机2PP-08 table/capsule counterPP-08全自动电子数粒机Pharmapack Packaging equipment co., LTD珐玛珈（广州）包装设备有限公司Table/capsule counter自动电子数粒机3PCI-18 inline screw-on caperPCI-18直线式旋盖机Pharmapack Packaging equipment co., LTD珐玛珈（广州）包装设备有限公司Inline screw-on caper直线式旋盖机4PS-20 induction cap sealerPS-20铝箔封口机Pharmapack Packaging equipment co., LTD珐玛珈（广州）包装设备有限公司Induction cap sealer铝箔封口机5PLB-1020 wrap-around labelerPLB-1020立式圆瓶贴标机Pharmapack Packaging equipment co., LTD珐玛珈（广州）包装设备有限公司Wrap-around labeler圆瓶贴标机6Leak tester 检漏测试仪PLT-03Jinan blue light mechanical and electrical co., LTD济南蓝光机电有限公司Leak tester 检漏测试Sr. No.序号Utility Name公用工程名称Equipment Code设备编号Validation Certificate No.验证证书编号1HVAC 空调净化系统PHV-01CF-PHV-012Purified water system 纯化水系统PPW-01CF-PPW-013Compressed Air system 压缩空气系统PCA-01CF-PCA-01S. No.序号Area Name房间名称Area Code房间编号AHU Number空调机组编号Validation Certificate No.验证证书编号1Bottle packing line 瓶装线P3037AHU-302CF-PHV-012Secondary Packing 外包装P3122AHU-301CF-PHV-0111.0 PACKAGING FLOW CHART:包装流程图Bottled line validation check project:瓶装线验证检查项目：1、Counter effectiveness数粒计数有效性2、Cap screwing machine test旋盖机测试3、Power experiment功率挑战实验4、Electromagnetic induction sealing machine rate challenge test电磁感应封口机速度挑战实验5、Label detection 标签检测 Bulk tablets桶装片Blister packaging瓶装线包装Manual packing手工装箱Shrinking packaging热收缩包装12.0 CRITICAL PROCESS PARAMETERS TO BE VALIDATED 关键工艺参数验证12.1Counter effectiveness计数有效性12.1.1 Counting system testing计数系统检测B. No.批号S. No.序号MEASURED PARAMETERS测试项目ACCEPTANCE CRITERIA检测标准TEST RESULTS测试结果Done by: Sign & date操作人签名/日期Checked by: Sign & date检查人签名/日期1From the triple shock plate into the bottle药粒经三级震荡盘落入药瓶Medicine flow is smooth tablets without damage phenomenon药粒流动正常、无堵塞、无破损、破碎现象合格不合格2The effectiveness of entrance electric eye入口电眼的有效性Electric eye detection failure stop running电眼被遮住时数粒机自动停止运行合格不合格3The effectiveness of export of electric eye出口电眼的有效性Electric eye detection failure stop running电眼光线被遮住时数粒机自动停止运行合格不合格4Reject剔废Bottle will be reject when the pill is not accurate当数粒不准确该药瓶会被剔除（数粒不准确的情况？）合格不合格1From the triple shock plate into the bottle药粒经三级震荡盘落入药瓶Medicine flow is smooth tablets without damage phenomenon药粒流动正常、无堵塞、无破损、破碎现象合格不合格2The effectiveness of entrance electric eye入口电眼的有效性Electric eye detection failure stop running电眼被遮住时数粒机自动停止运行合格不合格3The effectiveness of export of electric eye出口电眼的有效性Electric eye detection failure stop running电眼光线被遮住时数粒机 自动停止运行合格不合格4Reject剔废Bottle will be reject when the pill is not accurate当数粒不准确该药瓶会被剔除合格不合格1From the triple shock plate into the bottle药粒经三级震荡盘落入药瓶Medicine flow is smooth tablets without damage phenomenon药粒流动正常、无堵塞、无破损、破碎现象合格不合格2The effectiveness of entrance electric eye入口电眼的有效性Electric eye detection failure stop running电眼被遮住时数粒机自动停止运行合格不合格3The effectiveness of export of electric eye出口电眼的有效性Electric eye detection failure stop running电眼光线被遮住时数粒机 自动停止运行合格不合格4Reject剔废Bottle will be reject when the pill is not accurate当数粒不准确该药瓶会被剔除合格不合格12.1.2 Counter effectiveness下料计数准确性测试Test method测试方法Base on YLS - SOP - QA065 acceptable quality level (AQL) sampling test for automatic number machine accuracy. According to the AQL requirements and production batch sample quantity and quality determination of eligibility criteria, and then take samples by artificial to examine, to determine whether accurately the load依据 “YLS-SOP-QA065合格质量水平（AQL）”对自动数粒机准确性进行抽检测试。根据AQL要求和生产批量进行取样量和质量合格标准的确定，然后由人工对所取样品进行逐一检查，确定是否进行精确装量。 Allow more a grain or less a grain规定计数不准确的药瓶为设定值的1片Sample number（Unit：bottle）取样数量（单位：瓶）1250瓶Acceptance standard接受标准（AQL%）Unqualified number cannot exceed 2.5%不合格数量不能超过取样量的2.5%B. No.批次B. No.批号B. Size:批量Unqualified number（Unit：bottle）不合格数量（单位：瓶）TEST RESULTS测试结果The first batch 第一批150万片合格 不合格The second batch第二批150万片合格 不合格The three groups第三批150万片合格 不合格Done by: Sign & date:操作人员签名/日期Checked by: Sign &date:检查人签名/日期12.2 Cap screwing machine test旋盖机测试1 12.2.1 Electric eye test检测剔除电眼组测试B. No.批号S. No.序号MEASURED PARAMETER测试项目ACCEPTANCE CRITERIA检测标准RESULT测试结果DONE BY Sign & Date操作人签名/日期CHECKED BY Sign & Date检查人签名/日期1No cap will be reject无盖自动剔除No lid on the bottle will be rejected药瓶上没有被旋上瓶盖时，剔除气缸会有动作，剔除该不合格瓶合格 不合格2No cap will be reject无盖自动剔除No lid on the bottle will be rejected药瓶上没有被旋上瓶盖时，剔除气缸会有动作，剔除该不合格瓶合格 不合格3No cap will be reject无盖自动剔除No lid on the bottle will be rejected药瓶上没有被旋上瓶盖时，剔除气缸会有动作，剔除该不合格瓶合格 不合格1No cap will be reject无盖自动剔除No lid on the bottle will be rejected药瓶上没有被旋上瓶盖时，剔除气缸会有动作，剔除该不合格瓶合格 不合格2No cap will be reject无盖自动剔除No lid on the bottle will be rejected药瓶上没有被旋上瓶盖时，剔除气缸会有动作，剔除该不合格瓶合格 不合格3No cap will be reject无盖自动剔除No lid on the bottle will be rejected药瓶上没有被旋上瓶盖时，剔除气缸会有动作，剔除该不合格瓶合格 不合格1No cap will be reject无盖自动剔除No lid on the bottle will be rejected药瓶上没有被旋上瓶盖时，剔除气缸会有动作，剔除该不合格瓶合格 不合格2No cap will be reject无盖自动剔除No lid on the bottle will be rejected药瓶上没有被旋上瓶盖时，剔除气缸会有动作，剔除该不合格瓶合格 不合格3No cap will be reject无盖自动剔除No lid on the bottle will be rejected药瓶上没有被旋上瓶盖时，剔除气缸会有动作，剔除该不合格瓶合格 不合格12.2.2 No aluminum foil will be reject瓶盖无铝箔剔除检测B. No.批号S. No.序号MEASURED PARAMETER测试项目ACCEPTANCE CRITERIA检测标准RESULT测试结果DONE BY Sign & Date操作人签名/日期CHECKED BY Sign & Date检查人签名/日期1No aluminum foil will be reject瓶盖无铝箔剔除Lid no aluminum foil will be reject瓶盖上没有铝箔时，剔除气缸，剔除该不合格药瓶合格 不合格2No aluminum foil will be reject瓶盖无铝箔剔除Lid no aluminum foil will be reject药瓶旋上没有铝箔的瓶盖时，剔除气缸会有动作，剔除该不合格药瓶合格 不合格3No aluminum foil will be reject瓶盖无铝箔剔除Lid no aluminum foil will be reject药瓶旋上没有铝箔的瓶盖时，剔除气缸会有动作，剔除该不合格药瓶合格 不合格1No aluminum foil will be reject瓶盖无铝箔剔除Lid no aluminum foil will be reject药瓶旋上没有铝箔的瓶盖时，剔除气缸会有动作，剔除该不合格药瓶合格 不合格2No aluminum foil will be reject瓶盖无铝箔剔除Lid no aluminum foil will be reject药瓶旋上没有铝箔的瓶盖时，剔除气缸会有动作，剔除该不合格药瓶合格 不合格3No aluminum foil will be reject瓶盖无铝箔剔除Lid no aluminum foil will be reject药瓶旋上没有铝箔的瓶盖时，剔除气缸会有动作，剔除该不合格药瓶合格 不合格1No aluminum foil will be reject瓶盖无铝箔剔除Lid no aluminum foil will be reject药瓶旋上没有铝箔的瓶盖时，剔除气缸会有动作，剔除该不合格药瓶合格 不合格2No aluminum foil will be reject瓶盖无铝箔剔除Lid no aluminum foil will be reject药瓶旋上没有铝箔的瓶盖时，剔除气缸会有动作，剔除该不合格药瓶合格 不合格3No aluminum foil will be reject瓶盖无铝箔剔除Lid no aluminum foil will be reject药瓶旋上没有铝箔的瓶盖时，剔除气缸会有动作，剔除该不合格药瓶合格 不合格12.2.3 The rotate lid is not qualified and need to be removed 旋盖不良剔除B. No.批号S. No.序号MEASURED PARAMETER测试项目ACCEPTANCE CRITERIA检测标准RESULT测试结果DONE BY Sign & Date操作人签名/日期CHECKED BY Sign & Date检查人签名/日期1The rotate lid is not qualified and need to be removed旋盖不良剔除The rotate lid is not qualified and need to be removed药瓶上旋盖没有旋紧时，剔除气缸会有动作，剔除该不合格药瓶合格不合格2The rotate lid is not qualified and need to be removed旋盖不良剔除The rotate lid is not qualified and need to be removed药瓶上旋盖没有旋紧时，剔除气缸会有动作，剔除该不合格药瓶合格不合格3The rotate lid is not qualified and need to be removed旋盖不良剔除The rotate lid is not qualified and need to be removed药瓶上旋盖没有旋紧时，剔除气缸会有动作，剔除该不合格药瓶合格不合格1The rotate lid is not qualified and need to be removed旋盖不良剔除The rotate lid is not qualified and need to be removed药瓶上旋盖没有旋紧时，剔除气缸会有动作，剔除该不合格药瓶合格不合格2The rotate lid is not qualified and need to be removed旋盖不良剔除The rotate lid is not qualified and need to be removed药瓶上旋盖没有旋紧时，剔除气缸会有动作，剔除该不合格药瓶合格不合格3The rotate lid is not qualified and need to be removed旋盖不良剔除The rotate lid is not qualified and need to be removed药瓶上旋盖没有旋紧时，剔除气缸会有动作，剔除该不合格药瓶合格不合格1The rotate lid is not qualified and need to be removed旋盖不良剔除The rotate lid is not qualified and need to be removed药瓶上旋盖没有旋紧时，剔除气缸会有动作，剔除该不合格药瓶合格不合格2The rotate lid is not qualified and need to be removed旋盖不良剔除The rotate lid is not qualified and need to be removed药瓶上旋盖没有旋紧时，剔除气缸会有动作，剔除该不合格药瓶合格不合格3The rotate lid is not qualified and need to be removed旋盖不良剔除The rotate lid is not qualified and need to be removed药瓶上旋盖没有旋紧时，剔除气缸会有动作，剔除该不合格药瓶合格不合格12.2.4 Torsion test瓶盖扭力测试（异烟肼片17-26N/m）B. No.批号S. No.序号MEASURED PARAMETER测试项目ACCEPTANCE CRITERIA检测标准RESULT测试结果DONE BY Sign & Date操作人签名/日期CHECKED BY Sign & Date检查人签名/日期1Use torsion test machine ten bottles用瓶盖扭力测试仪连续检测检测10个药瓶的瓶盖扭力Torque values between 17 and 26 and numerical stability瓶盖扭力在17-26N/m之间并且数值稳定合格不合格2Use torsion test machine ten bottles用瓶盖扭力测试仪连续检测检测10个药瓶的瓶盖扭力Torque values between 17 and 26 and numerical stability瓶盖扭力在17-26N/m之间并且数值稳定合格不合格3Use torsion test machine ten bottles用瓶盖扭力测试仪连续检测检测10个药瓶的瓶盖扭力Torque values between 17 and 26 and numerical stability瓶盖扭力在17-26N/m之间并且数值稳定合格不合格1Use torsion test machine ten bottles用瓶盖扭力测试仪连续检测检测10个药瓶的瓶盖扭力Torque values between 17 and 26 and numerical stability瓶盖扭力在17-26N/m之间并且数值稳定合格不合格2Use torsion test machine ten bottles用瓶盖扭力测试仪连续检测检测10个药瓶的瓶盖扭力Torque values between 17 and 26 and numerical stability瓶盖扭力在17-26N/m之间并且数值稳定合格不合格3Use torsion test machine ten bottles用瓶盖扭力测试仪连续检测检测10个药瓶的瓶盖扭力Torque values between 17 and 26 and numerical stability瓶盖扭力在17-26N/m之间并且数值稳定合格不合格1Use torsion test machine ten bottles用瓶盖扭力测试仪连续检测检测10个药瓶的瓶盖扭力Torque values between 17 and 26 and numerical stability瓶盖扭力在17-26N/m之间并且数值稳定合格不合格2Use torsion test machine ten bottles用瓶盖扭力测试仪连续检测检测10个药瓶的瓶盖扭力Torque values between 17 and 26 and numerical stability瓶盖扭力在17-26N/m之间并且数值稳定合格不合格3Use torsion test machine ten bottles用瓶盖扭力测试仪连续检测检测10个药瓶的瓶盖扭力Torque values between 17 and 26 and numerical stability瓶盖扭力在17-26N/m之间并且数值稳定合格不合格S. No.序号Electromagnetic sealer power challenge experiment电磁封口机功率挑战实验MEASURED PARAMETERS测试参数ACCEPTANCE CRITERIA检测标准Record记录12.3Electromagnetic sealer power challenge experiment: only corresponds to the first time, with the maximum speed of 50 start conveyor, sealing machine power from the highest set as the same, 18 , 20 , 22 , 24 set minimum sealing power: the power at the same, for the sealing parameters of the initial inspection, if the parameters meet the standard, will be the same as the minimum sealing power. If you have any parameter under the power does not meet the standard for the next 18 for the same test, sealing power in ascending way for the above mentioned all the sealing power repeated the process, set the minimum sealing power. Maximum sealing power: power detection in 24 , sealing parameters, if all the parameters meet the standard, is set as the highest seal power 24 , such as more power under this parameter does not meet the standard for the next test may be repeated sealing power 22 , in descending order of the all the sealing capacity of the above mentioned repeatability test, determine the highest seal power. Corresponding to two consecutive batches then: for the first time to get qualified for packaging sealing power range, In the following review for the first time in two batches of the sealing power range.电磁封口机功率挑战实验:只对应于第一批次，以最大速度的50启动输送带，封口机功率从最高设为16、18、20、22、24设定最低封口功率：检查功率为16此时如果参数满足标准，则将16设为最低封口功率。如果在该功率下有参数未满足标准则对下一个封口功率18进行同样的测试，以升序方式对以上提到的所有封口功率重复进行此过程，设定最低封口功率。设定最高封口功率：检测功率为24此时如果所有参数满足标准，则将24设为最高封口功率，如再此功率下参数未满足标准则对下一封口功率22进行重复测试，以降序方式对以上提到的所有封口功率进行重复性测试，确定最高封口功率。对应于随后两个连续批次：以第一批次得到的合格封口功率范围进行包装，在随后的两个批次中复核第一批次中得到的封口功率范围。Appearance: visual inspection through electromagnetic induction sealing machine bottle neck appearance.外观：目检经过电磁感应封口机药瓶的瓶口外观。Sealing test: check 10 bottle sealing effect密封性测试：检查10瓶的密封效果。Appearance: all bottles 100% seal completely sealed, no defects or seal leakage phenomenon.外观：所有药瓶均100%密封完全、无封口缺陷或漏封现象。Sealing test: all test bottle to be 100% no leakage and seal well.密封性测试：所有检测的药瓶需100%无泄漏、密封完好。Comments: based on the first batch of test results, confirm and record all meet the requirements of minimum and maximum power parameters. Confirm the minimum and maximum sealing power, and set to the qualified sealing, upper and lower limit on the power. (in the packaging process implementation and undergo the same record in packaging batch records).注释：基于第一批测试结果，确认与记录所有满足要求的最低和最高功率参数。确认最低和最高封口功率，并设定为合格的封口功率上、下限。（在包装过程中实施并在包装批记录中进行相同记录）。12.3.1 TEST DATA FOR BLISTER PACKING STAGE: BATCH-1第一批次瓶装线包装验证测试数据