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产品工艺验证利巴韦林注射液（1ml：100mg）第1页共42页长治市三宝生化药业有限公司编号SBB2.8.5.6利巴韦林注射液生产工艺验证方案长治市三宝生化药业有限公司产品工艺验证利巴韦林注射液（1ml：100mg）第2页共42页方案制订签名日期方案会签签名日期生产技术部签名日期验证小组签名日期方案批准质量保证部日期产品工艺验证利巴韦林注射液（1ml：100mg）第3页共42页目录1.概述`````````````````````````````````````````````````````````````````````````````````````````````````````````````````````````````4`1.1.产品简述``````````````````````````````````````````````````````````````````````````````````````````````````````````````41.2.处方及依据``````````````````````````````````````````````````````````````````````````````````````````````````````````41.3.生产工艺流``````````````````````````````````````````````````````````````````````````````````````````````````````````5`2.验证目的````````````````````````````````````````````````````````````````````````````````````````````````````````````````````53.验证的范围```````````````````````````````````````````````````````````````````````````````````````````````````````````````64.验证各部门职责及组织结构```````````````````````````````````````````````````````````````````````````````65.验证准备````````````````````````````````````````````````````````````````````````````````````````````````````````````````````76.验证内容及实施``````````````````````````````````````````````````````````````````````````````````````````````````````8`6.1.洗瓶工序````````````````````````````````````````````````````````````````````````````````````````````````````````````86.2.配制工序```````````````````````````````````````````````````````````````````````````````````````````````````````````126.3.灌封工序```````````````````````````````````````````````````````````````````````````````````````````````````````````156.4.灭菌工序```````````````````````````````````````````````````````````````````````````````````````````````````````````206.5.灯检工序```````````````````````````````````````````````````````````````````````````````````````````````````````````246.6.包装工序```````````````````````````````````````````````````````````````````````````````````````````````````````````266.7.成品检验结果``````````````````````````````````````````````````````````````````````````````````````````````````287.偏差分析``````````````````````````````````````````````````````````````````````````````````````````````````````````````````298.验证结论``````````````````````````````````````````````````````````````````````````````````````````````````````````````````299.附表````````````````````````````````````````````````````````````````````````````````````````````````````````````````````````````299.1.设备一览表及生产能力```````````````````````````````````````````````````````````````````````````````309.2.设备性能验证确认及检查情况表```````````````````````````````````````````````````````````````319.3参加验证人员培训情况检查表````````````````````````````````````````````````````````````````````329.4.厂房与公用设施验证的确认和检查情况表`````````````````````````````````````````````349.5.空气净化系统、工艺用水系统验证的确认和检查情况表`````````````````359.6.计量器具检查情况表```````````````````````````````````````````````````````````````````````````````````````369.7.三批（按四批准备）验证使用的原料、辅料和安瓿供应商确认及检查情况表`````````````````````````````````````````````````````````````````````````````379.8.质量检验系统验证和准备情况表```````````````````````````````````````````````````````````````389.9.检验仪器检查情况表``````````````````````````````````````````````````````````````````````````````````````399.10检验试剂检查情况表````````````````````````````````````````````````````````````````````````````````````409.11质量监控点、监控内容、监控方法、监控频次表`````````````````````````````41产品工艺验证利巴韦林注射液（1ml：100mg）第4页共42页1.概述1.1.利巴韦林注射液（1ml：100mg）常温状态下是无色的澄明液体，属抗病毒药，用于呼吸道合胞病毒引起的病毒性肺炎与支气管炎。1.2.利巴韦林注射液组方较为简单，具体工艺处方如下：处方：物料名称1ml：100mg利巴韦林1000g氯化钠87g药用炭20g共制成10000支处方依据：中国药典2010年版二部批准文号：国药准字H19999232批准机构：国家药品监督管理局1.3.生产工艺流程：产品工艺验证利巴韦林注射液（1ml：100mg）第5页共42页该产品从2010年批准生产以来，处方和生产工艺没有发生变更，产品质量基本稳定，没有质量事故发生。2012年公司搬迁和GMP改造，厂房设施发生了变更，精滤、稀配制、灌封等工序的生产环境由原来万级洁净区变更为现在的A级洁净区，生产操作人员在原来知识的基础上按照新版GMP进行再次培训，无论从操作技术还是生产理念都有很大的提高。2.验证目的根据2010版GMP要求，通过对利巴韦林注射液(1ml：100mg)产品工艺的验证，判断生产系统各要素和生产过程中可能影响产品质量的各种工艺变化因素，对其整个生产过程进行验证，以保证在正常的生产条件下，生产出合格、均一、稳定的利巴韦林注射液。同利巴韦林氯化钠安瓿注射用水浓配粗滤洗配精滤灌封灯检包装入库粗洗过滤过滤精洗干燥灭菌冷却灭菌检漏活性炭外包装材料A级洁净区B级洁净区产品工艺验证利巴韦林注射液（1ml：100mg）第6页共42页时确定岗位SOP修订的合理性，分析影响产品质量的关键因素，纠正偏差，建立生产全过程的运行标准和监控标准，确保产品质量安全有效。3.验证的范围本次验证是在该产品正常生产所需的厂房设施、生产设备、仪器仪表、检验设施设备及检验方法均经过了验证和校验、参与验证的相关人员都经过培训的前提下，按照批准的生产工艺规程和岗位SOP进行严格监控下的正常生产；所有记录真实、准确；所有抽样检验严格按照批准的规程进行。当上述条件之一改变时，应重新验证。4.验证各部门职责及组织机构4.1验证组4.1.1负责验证方案的审批。4.1.2负责验证的协调工作，以保证本验证方案规定项目顺利实施。4.1.3负责验证数据及结果的审核。4.1.4负责验证报告的审批。4.1.5负责发放验证报告证书。4.1.6负责再验证周期的确认。4.2设备动力部4.2.1负责组织试验所需仪器、设备的验证。4.2.2负责仪器、仪表、量器等的校正。4.2.3负责设备的维护保养。4.3质保部4.3.1负责制定质量标准和检验操作规程。4.3.2负责制定取样方案并取样对样品进行检验。4.3.3负责起草验证方案。4.3.4负责收集各项验证、试验记录，并对试验结果进行分析后，起草验证告，报验证委员会。4.4生产组织部4.4.1负责拟定验证方案。4.4.2负责验证方案的实施。4.4.3负责设备操作。产品工艺验证利巴韦林注射液（1ml：100mg）第7页共42页4.5验证过程应严格按照本方案规定的内容进行，若因特殊原因确需变更时，应填写验证方案变更申请书，报验证组批准。5.验证准备5.1设备生产利巴韦林注射液(1ml：100mg)所用设备见附表1，所列设备均已通过验证和再验证见附表2。5.2.人员参加验证人员必须经过培训，培训结果及有关文件见附表3。.产品工艺验证利巴韦林注射液（1ml：100mg）第8页共42页6.验证实施按照确定的原辅料、包装材料、生产设备、检验仪器和试剂，由各验证小组按照验证方案，连续投料三批，每批**万支，进行生产工艺验证。6.1.洗瓶工序6.1.1.因素分析本工序主要控制参数有：a.洗瓶用水水温；b.注水机注满水率；c.甩水机甩净水率；d.终端精洗用水的可见异物；e.远红外隧道烘箱的灭菌温度和灭菌时间。以上因素中，甩水机甩水效果、注水机注满水率、终端精洗用水的可见异物检查等控制标