清洁验证风险评估，到底怎么打分？
本文给出了清洁验证风险评估时需要评估的风险因素及相应的评分示例，供大家参考！该示例适用于初始清洁验证风险评估、新产品引入或清洁程序变更的风险评估，它不是一份详尽的清单，药企可以根据实际情况进行适当的调整。Severity：严重性：Severity严重性Examples of Rating Factors评分示例54321Equipment Use设备使用Shared共用Dedicated专用Direct or Indirect直接或间接直接Product产品Excipient辅料Buffers缓冲液Type of Product产品类型Low ADE/PDE(high hazard)低ADE/PDE（高危害性）Rx (Prescription)处方药Over the Counter(OTC)非处方（OTC）药Nutritional营养产品Cosmetics化妆品HBEL基于健康的暴露限≤ 1 µg/day≤ 10 µg/day≥ 100 µg/dayStability of Active活性成分的稳定性Stable稳定25% deactivated/degraded25%失效/降解50% deactivated/Degraded50%失效/降解75% deactivated/Degraded75%失效/降解Completelydeactivated/Degraded完全无效/降解Route ofAdministration给药途径Intravenous静脉注射Oral口服Topical局部给药Cleaning Agents清洁剂Formulated按配方配制Commodity商品化清洁剂Water only水MicrobialConcerns微生物考虑Dry manufacturingprocessing step干燥的生产加工步骤Dry processing干燥的加工Bacteriostatic orlow-water activityProcess material抑菌或低水活度的加工物料Sanitization stepsprior to use使用前消毒Sterilization stepsprior to use使用前灭菌Proximity toPatient or FurtherPurification Steps临近使用前或进一步的净化步骤Filling*分装Formulation*配制Final Purification最终纯化Initial Purificationor Recovery初步净化或回收Fermentation发酵评分说明：5 = High Severity / 1 = Low Severity5=高严重性，1=低严重性Probability：可能性：Probability可能性Examples of Rating Factors评分示例54321Soil Type脏的类型Pastes糊状Solids固体Liquids液体Cleanability (Dueto Solubility orManufacturingProcess)可清洁性(根据溶解性或制造过程)Difficult to clean难以清洁Moderately hard toclean中度难清洁Easy to clean易于清洁CleaningReproducibility清洁可重现性Manual人工清洁Semiautomated半自动清洁Automated自动清洁Equipment Design设备设计Complex geometryand high numberof internalcomponents复杂的几何结构和大量的内部部件Simple geometryand high numberof internalcomponents简单的几何结构和大量的内部部件Complex geometrywith low numberof internalcomponents复杂的几何结构和少数的内部部件Simple geometrywith low numberof internalcomponents简单的几何结构和少数的内部部件Simple geometrywith no internalcomponents,except valve结构简单，没有内部部件，除了阀门Microbial Load微生物负荷Ambient processwater (WFI or PW)cleaning solutions常温工艺用水(WFI或PW)清洗Bacteriostatic orlow-water activityProcess material抑菌或低水活性工艺物料Hot process water(WFI or PW)cleaning solutions热的工艺用水(WFI或PW)清洗Caustic and/oracidic cleaningsolutions腐蚀性和/或酸性清洗液Steam inPlace (SIP) orsanitization stepsprior to use使用前进行在线蒸汽灭菌或消毒Deviations偏差Cleaning failuresdue to cleaningprocess failure由清洗过程失败导致清洁失效Cleaning failuresdue to systemfailures由系统故障导致清洁失效No known cleaningfailures无已知的清洁失效Age of CleaningValidation清洁验证的年限Over 20 years超过20年16 to 20 years16~20年11 to 15 years11~15年6 to 10 years6~10年Under 5 years5年内CV Results (WorstCase)清洁验证结果（最差情况）Above 51%达到清洁验证限度标准的51%21%–50%达到清洁验证限度标准的21~50%10%–20% of limit达到清洁验证限度标准的10~20%Below LOQ低于定量限Below LOD低于检测限Historical RoutineMonitoringTrending Data日常监测趋势历史数据Historically outsideof sigma超出西格玛Variable trendingHistory变化的历史趋势Consistenttrending withinsigma在西格玛内趋势稳定评分说明：5 = Higher Likelihood / 1 = Lower Likelihood5=高可能性，1=低可能性