高密度脂蛋白胆固醇测定试剂(盒)技术审评规范

高密度脂蛋白胆固醇测定试剂(盒)技术审评 高密度脂蛋白胆固醇测定试剂,盒,技术审评规范 ,2014版, 一、前言 本审评规范旨在指导注册申请人对高密度脂蛋白胆固醇测定试剂,盒,注册申报资料的准备及撰写～同时也为技术审评部门对注册申报资料的技术审评提供参考。 本审评规范是对高密度脂蛋白胆固醇测定试剂,盒,的一般要求～申请人应依据产品的具体特性确定其中内容是否适用～若不适用～需具体阐述理由及相应的科学依据～并依据产品的具体特性对注册申报资料的内容进行充实和细化。 本审评规范是对申请人和审查人员的指导性文件～但不包括注册审批所涉及的行政事项～亦不作为法规强制执行～如果有能够满足相关法规要求的其他～也可以采用～但需要提供详细的研究资料和验证资料～相关人员应在遵循相关法规的前提下使用本审评规范。 本审评规范是在现行法规和标准体系以及当前认知水平下制定的～随着法规和标准的不断完善～以及科学技术的不断发展～本审评规范相关内容也将适时进行调整。 二、适用范围 高密度脂蛋白胆固醇测定试剂,盒,用于体外定量测定人血清和/或血浆中的高密度脂蛋白胆固醇的含量。 从方法学考虑～本文主要指采用分光光度法原理～利用全自动、半自动生化分析仪或分光光度计～在医学实验室进行高密度脂蛋白胆固醇定量检验所使用的临床化学体外诊断试剂。本规范不适用于干式高密度脂蛋白胆固醇测定试剂,盒,。 依据《体外诊断试剂注册管理办法,试行,》,以下简称《办法》,高密度脂蛋白胆固醇测定试剂盒管理类别为?类～分类代号 1 为6840。 三、基本要求 ,一,综述资料 综述资料主要包括产品预期用途、临床意义、产品描述、有关生物安全性的说明、研究结果的总结评价以及同类产品上市情况介绍等内容～应符合《办法》和《体外诊断试剂注册申报资料基本要求》,国食药监械„2007‟609号,的相关要求。下面着重介绍与高密度脂蛋白胆固醇测定试剂,盒,预期用途有关的临床背景情况。 高密度脂蛋白(HDL)具有抵御斑块形成的作用～是一种抗动脉粥样硬化的脂蛋白。它的含量与动脉管腔狭窄程度呈负相关～高密度脂蛋白胆固醇,HDL-C,低于0.9mmol/L(35mg/dl)是冠心病危险因素～HDL-C增高～大于1.55mml/L(60mg/dl)被认为是冠心病负危险因素。HDL-C降低也多见于心、脑血管病～肝炎～肝硬化等患者。高脂血症往往伴低HDL-C。肥胖者HDL-C也多偏低。吸烟可使HDL-C下降。饮酒及长期体力活动会使HDL-C升高。测定人血清高密度脂蛋白胆固醇(HDL-C)含量是判别低高脂蛋白血症的重要指标。 注:若注册申报产品声称临床意义超出此内容范围～应提供相关文献或临床研究依据。 ,二,产品说明书 说明书承载了产品预期用途、试验方法、检测结果解释以及注意事项等重要信息～是指导实验室工作人员正确操作、临床医生针对检验结果给出合理医学解释的重要依据。因此～产品说明书是体外诊断试剂注册申报最重要的文件之一。产品说明书的格式应符合《体外诊断试剂说明书编写审评规范》的要求～结合《体外诊断试剂说明书编写指导原则》的要求～下面对高密度脂蛋白 2 胆固醇测定试剂,盒,说明书的重点内容进行详细说明～以指导注册申报人员更合理地完成说明书编制。 ?【产品名称】 ?试剂,盒,名称由三部分组成:被测物名称、用途、方法或原理。例如:高密度脂蛋白胆固醇测定试剂,盒,,直接法,选择抑制法,。 ?英文名称,如有,应当正确、完整、直译～不宜只写缩写。 ?【包装规格】 ?不得多于标准中所列的包装规格, ?注明装量或可测试的样本数～如〓〓测试/盒、〓〓mL。 ?【预期用途】 ?说明试剂盒用于体外定量测定人血清和/或血浆中高密度脂蛋白胆固醇的含量。 ?与预期用途相关的临床适应症背景情况～如临床适应症的发生率、易感人群等～相关的临床或实验室诊断方法等。 ?【检验原理】 本规范适用于对人血清和/或血浆中的高密度脂蛋白胆固醇进行定量检测的试剂,盒,～以下介绍几种典型反应原理: ?直接法-选择抑制法:血清中乳糜微粒,CM,、低密度脂蛋白,LDL,及极低密度脂蛋白,VLDL,在多聚阴离子及反应抑制剂作用下表面被遮蔽。HDL-C与表面活性剂、反应促进剂在胆固醇酶试剂作用下参与Trinder反应而显色～吸光度与标本中HDL-C浓度成正比。 ?直接法-过氧化氢酶清除法:反应分两步进行～试剂1中具有特异选择性的强离子缓冲液与表面活性剂作用于血清中CM、VLDL及LDL, 使其所含的胆固醇暴露～在胆固醇酯酶,CHER,和胆固醇氧化酶,CHOD,的催化反应下生成过氧化氢～过氧化氢被 3 过氧化氢酶分解而被清除。试剂2中的叠氮钠抑制了过氧化氢酶活性～另一表面活性剂使HDL颗粒中的胆固醇暴露～并与胆固醇酶试剂发生反应～通过Trinder反应可测定HDL-C。 ?直接法-PEG修饰酶法:在镁离子的存在下～α-环糊精硫酸盐与CM、VLDL、LDL形成可溶性复合物。这些复合物能抵抗变构酶的作用,PEG6000或葡聚糖右旋糖苷与胆固醇酯酶,CHER,和胆固醇氧化酶,CHOD,共价结合～引起酶的变构～变构酶对脂蛋白的大小和/或电荷具有选择性～其顺序依次为LDL、VLDL、CM和HDL。而α-环糊精硫酸盐能限制CM、VLDL颗粒进入环状的环糊状结构～从而避免酶的催化作用～这种作用还与镁离子浓度有关。因此在镁离子及少量硫酸葡聚糖存在的前提下～通过Trinder反应可测定HDL-C。 ?直接法-抗体分离法:反应分两步进行～试剂?中的抗人ApoB脂蛋白抗体首先与血清中的CM、VLDL、LDL结合形成不溶性抗原-抗体复合物,加入试剂?后～抗原-抗体复合物不与酶试剂起反应～只有HDL-C与酶试剂反应～生成过氧化氢～并通过Trinder反应可测定HDL-C含量。 ?【主要组成成份】 ?说明试剂盒包含组分的名称、数量、比例或浓度等信息～如果对于正确的操作很重要～应提供其生物学来源、活性及其他特性,明确说明不同批号试剂盒中各组分是否可以互换。 ?试剂盒内如包含校准品和/或质控品～应说明其主要组成成分及其生物学来源～校准品应注明其定值及溯源性～溯源性至少应写明溯源到的最高级别～包括:标准物质的发布单位及编号～质控品应有合适的靶值范围。 ?【储存条件及有效期】 ?对试剂盒的效期稳定性、复溶稳定性、开瓶稳定性等信息 4 做详细介绍。包括环境温湿度、避光条件等。 ?不同组分保存条件及有效期不同时～应分别说明～产品总有效期以其中效期最短的为准。 注:保存条件不应有模糊表述～如“室温”。稳定期限应以月或日为单位。 ?【适用仪器】 ?说明可适用的仪器～并提供与仪器有关的必要信息以便用户能够作出最好的选择。 ?应写明具体适用仪器的型号～不能泛指某一系列仪器。 ?【样本要求】重点明确以下内容: ?样本采集前对患者的要求:如采集时间、采集顺序等～是否受临床症状、用药情况等因素的影响。 ?样本采集:说明采集方法及样本类型～如有血浆样本～应注明对抗凝剂的要求。 ?样本处理及保存:样本处理方法、保存条件及期限、运输条件等。冷藏/冷冻样本检测前是否须恢复室温～冻融次数。对储存样本的添加剂要求等。 ,4,应明确当测定值超出线性上限时的稀释方法～并给出稀释最大倍数说明。 ?【检验方法】详细说明试验操作的各个步骤～包括: ?试验具体操作步骤。 ?试剂配制方法、注意事项。 ?试验条件:温度、时间、仪器波长等以及试验过程中的注意事项。 ?校准:校准品的使用方法、注意事项、校准曲线的绘制。应注明推荐的仪器校准周期。 ?质量控制:质控品的使用方法、对质控结果的必要解释以 5 及推荐的质控周期等～如质控不合格应提供相关的解决。 ?【参考值,参考范围,】 ?应注明常用样本类型的正常参考值,范围,～如健康成年男性:1.16，1.42mmol/L,健康成年女性:1.29，1.55mmol/L。并简要说明参考值确定的方法。 ?简单介绍设定该参考值,范围,所选健康人群的区域特征～建议注明以下字样“由于地理、人种、性别及年龄等差异～建议各实验室建立自己的参考值,范围,”。 ?【检验结果的解释】 说明可能对试验结果产生影响的因素,说明在何种情况下需要进行确认试验。 ?【检验方法局限性】 ?说明检测结果仅供临床参考～不能单独作为确诊或排除病例的依据。 ?说明该检验方法由于哪些原因会使测量结果产生偏离～或测量结果还不能完全满足临床需要。如:干扰,胆红素、血红蛋白、甘油三酯等,等。 ?【产品主要性能指标】 产品性能指标应符合企业标准要求。说明该产品主要性能指标～应至少包括:外观、装量、试剂空白吸光度、试剂空白吸光度变化率、分析灵敏度、线性范围、重复性、批间差等。 ?【注意事项】应至少包括以下内容: ?本试剂盒的检测结果仅供临床参考～对患者的临床诊治应结合其症状/体征、病史、其他实验室检查及治疗反应等情况综合考虑。 ?使用不同生产商的试剂对同一份样本进行检测可能会存在差异。 6 ?对所有样本和反应废弃物都应视为传染源对待～提示操作者采取必要的防护措施。 ?【参考文献】 注明引用参考文献～其书写应清楚、易查询且格式规范统一。 ?【生产企业】 包括企业名称、地址,注册地址和生产地址不同的应分别列出,、邮政编码、电话和传真号码、网址等。 ?【其他】 如医疗器械生产企业许可证编号、医疗器械注册证书编号、产品标准编号、说明书批准日期及修订日期等。 ,三,拟定产品标准及编制说明 拟定产品标准应符合《体外诊断试剂注册管理办法》和《体外诊断试剂注册申报资料基本要求》的相关规定。如已有相应的国家/行业标准发布～则企业标准的要求不得低于其相关要求。 下面就标准中涉及的产品适用的相关标准、主要性能指标、标识标签说明书以及检验规则等相关内容做一简要叙述。 ?产品适用的相关标准 ?GB/T 191-2008 包装储运图示标志 ?GB/T 21415—2008 体外诊断医疗器械 生物样品中量的测量 校准品和控制物质赋值的计量学溯源性 ?GB/T 26124-2011 临床化学体外诊断试剂,盒, ?YY/T 0316-2008 医疗器械 风险管理对医疗器械的应用 ?YY/T 0466.1,2009医疗器械 用于医疗器械标签、标记和提供信息的符号 第1部分:通用要求 ?主要性能指标: ,1,外观 a)试剂盒各组分应齐全、完整～液体无渗漏, 7 b)包装标签文字符号应清晰。 ,2,装量 液体试剂的净含量应不少于标示量。 ,3,试剂空白吸光度 用指定空白样品测试试剂,盒,～在说明书规定的测试条件下～反应结束(T)后的吸光度,A,～测试结果即为试剂空白吸光度测定值～应不大于0.05。 ,4,分析灵敏度 已知浓度在,1.00，2.00,mmol/L的样本～记录在试剂,盒,规定参数下的吸光度差值。换算为1.00mmol/L的吸光度差值～两点终点法吸光度差值,ΔA,应>0.04,两点速率法吸光度差值,ΔA/min,应>0.01。 ,5,线性 用接近线性区间下限的低浓度样本稀释接近线性区间上限的高浓度样本～混合成6个稀释浓度,xi,。用试剂,盒,分别测试以上样本～每个稀释浓度测试3次～分别求出每个稀释浓度检测结果的均值,yi,。以稀释浓度,xi,为自变量～以检测结果均值,yi,为因变量求出线性回归方程。按公式,1,计算线性回归的相关系数 [(x-x)(yy)],,ii,r,。 r,22(x-x)(y-y),,ii ……………………………………,1, ,代入求出线性回归方程～计算yi的估计值及稀释浓度,xi yi与估计值的相对偏差或绝对偏差。 试剂,盒,至少在[0.20～2.50]mmol/L的线性范围内分析性能应符合如下要求: ?线性相关系数,r,应不小于0.995, ?[0.20～2.50]mmol/L区间内～线性偏差应不超过〒0.10mmol/L或不超过〒10,。 8 ,6,重复性 ?批内重复性:分别用试剂,盒,重复测试,0.80〒0.20,mmol/L和,1.50〒0.50,mmol/L的血清样品或质控样品～重复测 x试10次～分别计算测量值的平均值,,和标准差,s,。所得结果的变异系数,CV,应不大于4%。 ?批内瓶间差,干粉或冻干试剂适用, 用(1.50〒0.50) mmol/L的血清样品或质控样品测试同一批 x号的10个待检试剂,盒,～并计算10个测量值的平均值,1,和标准差,s1,。 用(1.50〒0.50) mmol/L的血清样品或质控样品对该批号的1 x个待检试剂,盒,重复测试10次～计算结果的均值,2,和标准差,s2,。按公式,2,、,3,计算瓶间差的变异系数,CV,。 22s,s,s瓶间12 ……………………………………,2, CV,sx，100%1瓶间 ……………………………………,3, 当s1,s2时～令CV=0 每个浓度下试剂,盒,批内瓶间差均应不大于4%。 ,7,批间差:用,1.50〒0.50,mmol/L的血清样品或质控样品分别测试3个不同批号的试剂,盒,～每个批号测试3次～分别 xi计算每批3次测定的均值(i=1,2,3)～按公式,4,、,5,计算相对极差,R,。 x，x，x123x,T3 ………………………………………,4, x,xmaxminR,，100% xT ……………………………………,5, 式中: xxmaxi,中的最大值, xximin ,中的最小值。 试剂,盒,批间相对极差,R,应不大于10%。 9 ,8,准确度 ?相对偏差 试剂,盒,测试可用于评价常规方法的有证参考物质(CRM)或其它公认的参考物质3次～测试结果记为,X,～按公式,6,分别i 计算相对偏差B～如果3次结果的相对偏差应不超过〒10%～即判为合格。如果大于等于2次的结果不符合～即判为不合格。如果有1次结果不符合要求～则应重新连续测试20次～并分别按照公式,6,计算相对偏差～如果大于等于19次测试结果的相对偏差应不超过〒10%～即判为合格。 B%,(Xi,T),T〓100% ……………………………,6, 式中:Xi为测试值, T为标准物质标示值～或各浓度人血清定值。 ?比对试验 用不少于40个在检测浓度范围内不同浓度的临床样品～以生产企业指定的分析系统作为比对方法～每份样品按待测试剂,盒,操作方法及比对方法分别检测。用线性回归方法计算两组结果的相关系数,r,及每个浓度点的相对偏差。相关系数 r?0.995～[0.20～2.50]mmol/L区间内～线性偏差应不超过〒0.10mmol/L或不超过〒10,。 注: 1.型式试验时～按以上优先顺序～采用上述方法之一测试试剂,盒,的准确度。 2.出厂检验时～生产企业可以选择以上检验方式～也可以使用具有溯源性的企业,工作,校准品或正确度质控物质进行准确度实验。 ,9,效期稳定性 ?效期稳定性:试剂,盒,在规定的贮存条件下保存至有效 10 期末～产品的性能应至少符合线性、准确度和重复性的要求。 ?复溶稳定性,干粉或冻干试剂适用,:干粉试剂开瓶后,复溶后,在规定的贮存条件下保存至预期时间内～产品的性能应至少符合线性、准确度和重复性。 ,10,校准品和质控品,如适用, ?溯源及赋值说明:高密度脂蛋白胆固醇已有国家及国际标准物质～试剂盒配套校准品和质控品～应参照GB/T 21415—2008《 体外诊断医疗器械 生物样品中量的测量 校准品和控制物质赋值的计量学溯源性》的要求溯源至国家或国际标准物质～并提供校准品溯源性说明及质控品赋值说明。 ?性能要求:外观、装量、质控品赋值有效性、干粉或冻干品应包含批内瓶间差、复溶稳定性。 ?试剂,盒,说明书、标签、包装标识 ?试剂,盒,说明书,详见“产品说明书”相关要求, ?外包装标签 ?生产企业名称和地址。 ?试剂,盒,名称。 ?批号。如试剂,盒,包含不同批号的组件～外包装的批号应能保证每个组件的批号可从生产企业的生产记录中溯源。 ?规格型号。应包含体积或复溶后的体积。 ?预期用途。如试剂,盒,名称不能反映试剂,盒,的预期用途～应提供简要的预期用途说明。 ?体外诊断用途。 ?储存和处臵条件。应提供在未开瓶状态下可保证试剂,盒,的稳定状态的必要储存条件,应规定影响稳定性的其他条件,如适用,,应规定产品处臵时所采取的所有其他特殊措施,如适用,。 11 ?失效期。应明示在规定储存条件下的失效期,失效期应以年、月～适当时以日表示,如仅给出年月～失效期应为指定月最后一天,外包装标签上明示的失效期应为最早到期组件的失效期。 ?警告和预防措施。如体外诊断试剂,盒,被认为有危险性,例如:化学～放射性或生物危害性,～外包装应标有适当的警示危险的文字或符号～YY/T 0316的要求适用,对于化学危害～如试剂,盒,没有随带含有适当的危险和安全性说明的使用说明～则应在外包装的标签上进行说明。 ?初始包装标签 如初始包装同时也是外包装～则外包装标签的要求也适用。 ?生产企业名称或等同的商标或标志。 ?产品名称。 ?批号。 ?规格型号。 ?体外诊断用途。 ?储存和处臵条件,参见外包装标签要求,。 ?失效期,参见外包装标签要求,。 ?警告和预防措施,参见外包装标签要求,。应明示试剂预期为一次性使用。 ?出厂检验原则 每批试剂,盒,出厂检验至少进行以下几项内容:外观、装量、试剂空白吸光度、准确度、重复性、赋值有效性,如适用,。 ,四,注册检测 根据《办法》要求～首次申请注册的第二类产品应该在国家食品药品监督管理总局认可的、具有相应承检范围的医疗器械检测机构进行三个生产批次样品的注册检测。对于已经有国家标准品的检测项目～在注册检测时应采用相应的国家标准品进行。 12 ,五,主要原材料研究资料,如需提供, 主要原材料,包括酶、底物及其他主要原料,的选择、制备、质量标准及实验验证研究资料,质控品、校准品的原料选择、制备、定值过程及试验资料,校准品的溯源性文件～包括具体溯源链、实验方法、数据及统计分析等详细资料。 ,六,主要生产工艺及反应体系的研究资料,如需提供, 1.主要生产工艺介绍～可以图表方式表示, 2.反应原理介绍, 3.确定反应所需物质用量,校准品、样本、酶、底物等,的研究资料, 4.确定反应最适条件研究, 5.其他:如基质效应等。 ,七,分析性能评估资料 企业应提交在产品研制阶段对试剂盒进行的所有性能验证的研究资料～包括具体研究方法、试验数据、统计方法等详细资料。申请人应按以下要求提供体外诊断试剂性能评估资料: ?申请人名称, ?性能评估方法、要求, ?性能评估所使用试剂,包括校准品、质控品,的名称、批号、有效期, ?应提供使用的仪器型号、序列号,SN,, ?性能评估的时间、地点、检验人员, ?性能评估的具体数据及分析判定, ?性能评估审批人签字、审批时间。 对于本试剂盒～建议着重对以下分析性能进行研究: ?准确度 13 对测量准确度的评价依次包括:与国家标准品,和/或国际标准品,的偏差分析、方法学比对等方法～企业可根据实际情况选择合理方法进行研究。 ,1, 与国家,国际,标准品的比对研究 该研究项目已有相应国家,国际,标准品～优先使用国家,国际,标准品进行验证～重点观察对相应标准品检测结果的偏差情况。 ,2, 方法学比对 在国家,国际,标准品无法获得的前提下～可采用普遍认为质量较好的已上市同类试剂作为参比方法～与拟申报试剂同时检测一批临床样品～从测定结果间的差异了解拟申报试剂与参比方法间的偏倚。如偏倚很小或在允许的误差范围内～说明两检测系统对病人标本测定结果基本相符～对同一份临床样本的医学解释～拟申报试剂与参比方法相比不会产生差异结果。 在实施方法学比对前～应分别对拟申报试剂和参比试剂进行初步评估～只有在确认两者都分别符合各自相关的质量标准后方可进行比对试验。方法学比对时应注意质量控制、样本类型、浓度分布范围并对结果进行合理的统计学分析。 ?试剂空白吸光度 用指定空白样品测试试剂,盒,～在说明书规定参数下～记录测试反应完成(T)后的吸光度,A,～测试结果即为试剂空白吸光度测定值～试剂空白吸光度应<0.05。 注:空白样本可以是纯水样本、生理盐水、零校准液等。 ?分析灵敏度 用试剂,盒,测试高密度脂蛋白胆固醇已知浓度在,1.00，2.00,mmol/L的样本～记录在试剂,盒,规定参数下的吸光度差值～换算为1.00mmol/L的吸光度差值～两点终点法吸光度差值,Δ 14 A,应>0.04,两点速率法吸光度差值,ΔA/min,应>0.01。 ?批内重复性 测量重复性的评估应包括两个浓度水平的样本进行～建议浓度为,0.80〒0.20,mmol/L和,1.50〒0.50,mmol/L～两个浓度都应在试剂盒的测量范围内。 ?批间差 用,1.50〒0.50,mmol/L的血清样品或质控样品分别测试3个不同批号的试剂,盒,～每个批号测试3次～分别计算每批3次测定的均值～计算相对极差,R,应不大于10%。 ?线性范围 建立试剂线性范围所用的样本基质应尽可能与临床实际检测的样本相似～理想的样本为分析物浓度达到预期测定上限的混合人血清～且应充分考虑多倍稀释对样本基质的影响。建立定量产品的线性范围时～需在预期测定范围内选择至少7-11个浓度水平。例如～将预期测定范围加宽至130%～在此范围内选择更多的浓度水平～然后依据实验结果逐渐减少数据点,最终不得少于7个水平,直至表现出线性关系～可发现最宽的线性范围。 ?干扰试验 对样本中常见的干扰物质进行检测～如胆红素、血红蛋白、甘油三酯等。方法为对模拟添加样本分别进行验证～样本量选择应体现一定的统计学意义～说明样本的制备方法及干扰实验的评价标准～确定可接受的干扰物质极限浓度。 ?校准品溯源及质控品赋值 应参照GB/T 21415—2008《 体外诊断医疗器械 生物样品中量的测量 校准品和控制物质赋值的计量学溯源性》的要求～提供企业,工作,校准品及试剂盒配套校准品定值及不确定度计算记录～提供质控品赋值及其靶值范围确定的记录。 15 ?其他需注意问题 对于适用多个机型的产品～应提供如产品说明书【适用机型】项中所列的所有型号仪器的性能评估资料。 试剂盒的样本类型如包括血清和血浆样本～则应对二者进行相关性研究以确认二者检测结果是否完全一致或存在某种相关性,如系数关系,。对于血浆样本～企业应对不同的抗凝剂进行研究以确认最适的抗凝条件以及是否会干扰检测结果。 ,八,参考值,参考范围,确定资料 应提交建立参考值,范围,所采用样本来源及详细的试验资料。应明确参考人群的筛选标准～研究各组,如性别、年龄等,例数不应低于120例。 若引用针对中国人群参考值范围研究的相关文献～应明确说明出处～并进行验证。参考值研究结果应在说明书【参考值,范围,】项中进行相应说明。 ,九,稳定性研究资料 稳定性研究主要包括效期稳定性、高温加速破坏稳定性、运输稳定性、机载稳定性及开瓶,复溶,稳定性等～企业可根据实际需要选择合理的稳定性研究方案。稳定性研究资料应包括研究方法的确定依据、具体方法及过程。对于实时稳定性研究～应提供至少3批样品在实际储存条件下保存至成品有效期后的研究资料。 应对样本在不同储存条件下的稳定性期限进行研究～并在说明书中样本要求处明示。,注:若有相关文献中已明确说明～亦可作为依据。, ,十,临床试验研究 试剂,盒,按照《办法》及《体外诊断试剂临床研究技术指导原则》、《北京市第二类体外诊断试剂临床试验指导原则》进行 16 临床试验。 ?研究方法 选择境内已批准上市的性能相近的同类产品作为参比试剂～采用拟申报产品,以下称考核试剂,与之进行对比试验研究～证明本品与已上市产品等效。 ?临床研究单位的选择 应选择至少两家省级卫生医疗机构～临床研究单位实验操作人员应有足够的时间熟悉检测系统的各环节,试剂、质控及操作程序等,～熟悉评价方案。在整个实验中～考核试剂和参比试剂都应处于有效的质量控制下～最大限度保证试验数据的准确性及可重复性。 ?临床试验方案 临床试验实施前～研究人员应从流行病学、统计学、临床医学、检验医学等多方面考虑～科学合理的临床研究方案。各临床研究机构的方案设臵应保持一致～且保证在整个临床试验过程中遵循预定的方案实施～不可随意改动。整个试验过程应在临床研究机构的实验室内并由本实验室的技术人员操作完成～申报单位的技术人员除进行必要的技术指导外～不得随意干涉实验进程～尤其是数据收集过程。 试验方案中应确定严格的病例纳入/排除标准～任何已经入选的病例再被排除出临床研究都应记录在案并明确说明原因。在试验操作过程中和判定试验结果时应采用盲法以保证试验结果的客观性。各研究单位选用的参比试剂及所用机型应保持一致～以便进行合理的统计学分析。另外～考核试剂的样本类型应与产品说明书一致～且不应超越参比试剂对样本类型的检测要求～如果选择了参比试剂适用样本类型以外的样本～则应采用临床金标准对额外的样本类型进行验证。 17 ?研究对象选择 临床试验应选择具有特定症状/体征人群作为研究对象。企业在建立病例纳入标准时～应考虑到不同人群的差异～尽量覆盖各类适用人群。在进行结果统计分析时～建议对各类人群分别进行数据统计分析。 研究总体样本数不少于200例～应充分考虑对病理值样本的验证～异常值样本数建议不少于80例。样本中待测物浓度应覆盖考核试剂线性范围～且尽可能均匀分布。 血清/血浆应明确抗凝剂的要求、存贮条件、可否冻融等要求及避免使用的样本。实验中～尽可能使用新鲜样本～避免贮存。如无法避免使用贮存样品时～注明贮存条件及时间～在数据分析时应考虑其影响。 如果声称同时适用于血清/血浆/全血样本～那么血清,或血浆或全血,的试验例数参照上述要求～并应同时验证其中至少50例受试者的自身血清、血浆和/或全血样本测试结果间的一致性,采用考核试剂评价,～其中不同浓度样本分布情况与总例数中分布情况应一致。 ?统计学分析 对临床试验结果的统计应选择合适的统计方法～如相关分析、线性回归、配对t检验、绝对偏倚及相对偏倚分析等。对于对比实验的等效性研究～最常用是对考核试剂和参比试剂两组检测结果的相关及线性回归分析～应重点观察相关系数,r值,或判定系 2数,R,、回归拟合方程,斜率和y轴截距,等指标。结合临床试验数据的正/偏态分布情况～建议统计学负责人选择合理的统计学方法进行分析～统计分析应可以证明两种方法的检测结果无明显统计学差异。在临床研究方案中应明确统计检验假设～即评价考核试剂与参比试剂是否等效的标准。 18 ?临床试验总结报告撰写 根据《体外诊断试剂临床研究技术指导原则》的要求～临床试验报告应该对试验的整体设计及各个关键点给予清晰、完整的阐述～应该对整个临床试验实施过程、结果分析、结论等进行条理分明的描述～并应包括必要的基础数据和统计分析方法。建议在临床总结报告中对以下内容进行详述。 ?临床试验总体设计及方案描述 ?临床试验的整体管理情况、临床研究单位选择、临床主要研究人员简介等基本情况介绍。 ?病例纳入/排除标准、不同人群的预期选择例数及标准。 ?样本类型～样本的收集、处理及保存等。 ?统计学方法、统计软件、评价统计结果的标准。 ?具体的临床试验情况 ?考核试剂和参比试剂的名称、批号、有效期及所用机型等信息, ?对各研究单位的病例数、人群分布情况进行总合～建议以列表或图示方式给出具体例数及百分比。 ?质量控制～试验人员培训、仪器日常维护、仪器校准、质控品运行情况～对检测精密度、质控品回收,或测量值,、抽查结果评估。 ?具体试验过程～样本检测、数据收集、样本长期保存等。 ?统计学分析 ?数据预处理、对异常值或离群值的处理、研究过程中是否涉及对方案的修改。 ?定量值相关性和一致性分析 2用回归分析验证两种试剂结果的相关性～以y=a+bx和R的形式给出回归分析的拟合方程～其中:y是考核试剂结果～x是参比 19 2试剂结果～b是方程斜率～a是y轴截距～R是判定系数,通常要 2求R?0.95,～同时应给出b的95%,或99%,臵信区间。,对于理想的可信区间～回归系数应涵盖“1”, 截距应涵盖“0”,。 给出考核试剂与参比试剂之间的差值,绝对偏倚/偏差,及比值,相对偏倚/偏差,散点图～观察并分析各点的偏倚分布情况。分别计算男性、女性医学决定水平处相对偏倚/偏差及95%臵信区间。其医学决定水平处允许相对偏倚/偏差限值应不大于10%。 ?讨论和结论 对总体结果进行总结性描述并简要分析试验结果～对本次临床研究有无特别说明～最后得出临床试验结论。 四、名词解释 ?准确度,accuracy,:一个测量值与可接受的参考值间的一致程度。 2.分析灵敏度,Lower detection limit,:以足够臵信度可检测的最小浓度差异～按照IUPAC,国际理论,化学,与应用化学联合会,定义分析灵敏度代表校准曲线的斜率。 3.线性,linearity,:在给定测量范围内～给出的测量结果与样品中实际存在的被测量物的值成比例的能力。线性是描述一个测量系统的测量示值或测量结果相关于样本的赋值符合直线的属性。 4.精密度,precision,:在规定条件下～相互独立的测试结果之间的一致程度。精密度的程度是用统计学方法得到的测量不精密度的数字形式表示～如标准差,SD,和变异系数,CV,。 5.正确度质控物质,trueness control material,:用于评价测量系统测量偏倚的参考物质。 6.参考物质,reference material,:一种或多种指定特性足够均匀和稳定～已被证明适合在测量过程中或名义特性检验中预 20 期应用的物质。 注:只有具有指定量值的参考物质可用于校准或测量正确度控制。 五、参考文献 ?《体外诊断试剂注册管理办法,试行,》,国食药监械[2007]229号, ?《体外诊断试剂临床研究技术指导原则》,国食药监械[2007]240号, ?《体外诊断试剂说明书编写指导原则》,国食药监械[2007]240号, ?《北京市第二类体外诊断试剂临床试验指导原则》 ?全国临床检验操作规程,第3版,～中华人民共和国卫生部医政司 ?GB/T21415-2008《体外诊断医疗器械生物样品中量的测量校准品和控制物质赋值的计量学溯源性》 21 《高密度脂蛋白胆固醇测定试剂(盒)技术审评规范》 编制说明 一、编写目的 2007年《体外诊断试剂注册管理办法》,试行,、《体外诊断试剂临床研究技术指导原则》、《体外诊断试剂说明书编写指导原则》均已发布～编制本指导原则旨在指导和规范高密度脂蛋白胆固醇测定试剂,盒,产品的技术审评工作～帮助审评人员理解和掌握该类产品原理、组成、性能、预期用途等内容～把握技术审评工作基本要求和尺度～对产品安全性、有效性作出系统评价。 由于高密度脂蛋白胆固醇测定试剂,盒,产品仍在不断发展～审查员仍需从风险分析的角度认真确认申报产品的预期用途与风险管理是否相当,由于我国医疗器械法规框架仍在构建中～审查员仍需密切关注相关法规、标准及最新进展～关注审评产品实际组成、原理、预期用途等方面的个性特征～以保证产品审评符合现行法规安全、有效的要求。 二、编写依据 ,一,《医疗器械监督管理条例》,国务院令第276号, ,二,《体外诊断试剂注册管理办法》,试行,,国食药监械„2007‟229号, ,三,《体外诊断试剂临床研究技术指导原则》,国食药监械„2007‟240号, ,四,《体外诊断试剂说明书编写指导原则》,国食药监械„2007‟240号, ,五,GB/T 26124-2011《临床化学体外诊断试剂(盒)》 ,六,《高密度脂蛋白胆固醇测定试剂,盒,,报批稿,》行业标准 ,七,国家食品药品监督管理部门发布的其他规范性文件 22 三、指导原则中部分内容的说明 1. 本指导原则适用于采用直接法原理～利用全自动、半自动生化分析仪或分光光度计～在医学实验室进行高密度脂蛋白胆固醇定量检验所使用的临床化学体外诊断试剂。采用其他方法学原理测定高密度脂蛋白胆固醇的体外诊断试剂可借鉴参考本文中相关内容。 2.产品的具体性能指标主要参考了《高密度脂蛋白胆固醇测定试剂,盒,,报批稿,》行业标准, 3.对于准确度要求～考虑到行业内普遍反映出厂检验批次多～标准物质用量大、费用高～企业难以承受。故建议型式检验时～使用标准物质评价～出厂检验时～生产企业可以选择型式检验方式～也可以使用具有溯源性的企业,工作,校准品或正确度质控物质进行评价。 4.临床试验在遵循《体外诊断试剂临床研究技术指导原则》,国食药监械„2007‟240号,的前提下～参考NSLI EP9-A2《用患者样本进行方法比对及偏倚评估》细化补充了试验管理和统计分析方面的内容。 5.文中涉及的术语和定义参考ISO18113系列标准确定, 6.产品的临床意义、主要性能及临床试验要求先后征求了卫生部临床检验中心、北京医院、北京协和医院、北京安贞医院、北京煤炭总医院临床专家的意见。还征求了部分北京生产企业的意见。 四、指导原则编写人员 本指导原则的编写成员由北京市医疗器械注册技术审评人员、行政审批人员、临床专家共同组成～以充分利用各方面的信息和资源～综合考虑指导原则中各个方面的内容～尽量保证指导原则正确、全面、实用。 23 24 (英文版 ) Two regulations promulgated for implementation is in the party in power for a long time and the rule of law conditions, the implementation of comprehensive strictly strategic plan, implementation in accordance with the rules and discipline to manage the party, strengthen inner-party supervision of major initiatives. The two regulations supporting each other, the < code > adhere to a positive advocate, focusing on morality is of Party members and Party leading cadres can see, enough to get a high standard; < rule > around the party discipline, disciplinary ruler requirements, listed as "negative list, focusing on vertical gauge, draw the party organizations and Party members do not touch the" bottom line ". Here, the main from four square face two party rules of interpretation: the first part introduces two party Revised regulations the necessity and the revision process; the second part is the interpretation of the two fundamental principles of the revision of laws and regulations in the party; the third part introduces two party regulations modified the main changes and needs to grasp several key problems; the fourth part on how to grasp the implementation of the two regulations of the party. < code > and < Regulations > revised the necessity and revised history of the CPC Central Committee the amendment to the Chinese Communist Party members and leading cadres honest politics several guidelines > and < Chinese Communist Party discipline and Punishment Regulations > column 1 by 2015 to strengthen 25 party laws and regulations focus. Two party regulations revision work lasted a Years, pooling the wisdom of the whole party, ideological consensus, draw historical experience, respect for the wisdom of our predecessors, which reflects the unity of inheritance and innovation; follow the correct direction, grasp the limited goals, adhere to the party's leadership, to solve the masses of the people reflect a focus on the problem. The new revision of the < code > and < rule >, reflects the party's 18 and the eighth session of the third, the spirit of the fourth plenary session, reflecting the experience of studying and implementing the General Secretary Xi Jinping series of important speech, reflects the party's eighteen years comprehensive strictly practice. (a) revised two regulations of the party need of < the ICAC guidelines > in < in 1997 Leaders as members of the Communist Party of China clean politics certain criteria (Trial) > based on revised, the promulgation and implementation of January 2010, to strengthen the construction of the contingent of leading cadres play an important role. But with the party to manage the party strictly administering the deepening, has not been able to fully meet the actual needs. Content is too complicated, "eight prohibition, 52 are not allowed to" hard to remember, and also difficult to put into practice; the second is concisely positive advocated by the lack of prohibited provisions excessive, no autonomy requirements; the third is banned terms and discipline law, both with the party discipline, disciplinary regulations 26 repeat and Criminal law and other laws and regulations repeat; the fourth is to "clean" the theme is not prominent, not for the existing problems, and is narrow, only needle of county-level leading cadres above. < rule > is in 1997 < Chinese Communist Party disciplinary cases (Trial) > based on revision, in December 2003 the promulgation and implementation, to strengthen the construction of the party play very important role. Along with the development of the situation, which many provisions have been unable to fully meet the comprehensive strictly administering the practice needs. One is Ji law, more than half of the provisions and criminal law and other countries laws and regulations Repetition; two is the political discipline regulations is not prominent, not specific, for violation of the party constitution, damage the authority of Party Constitution of misconduct lack necessary and serious responsibility to pursue; third is the main discipline for the leading cadres, does not cover all Party members. Based on the above situation, need to < the criterion of a clean and honest administration > and < rule > the two is likely to be more relevant regulations first amendment. By revising, really put the authority of Party discipline, the seriousness in the party tree and call up the majority of Party members and cadres of the party constitution of party compasses party consciousness. (II) two party regulations revision process the Central Committee of the Communist Party of China attaches great importance to two regulations revision . Xi Jinping, general books recorded in the Fifth 27 Plenary Session of the eighth session of the Central Commission for Discipline Inspection, on the revised regulations < > made clear instructions. According to the central deployment, the Central Commission for Discipline Inspection from 2014 under six months begin study two regulations revision. The Standing Committee of the Central Commission for Discipline Inspection 4 review revised. Comrade Wang Qishan 14 times held a special meeting to study two regulations revision, amendment clarifies the direction, major issues of principle, path and target, respectively held a forum will listen to part of the province (area) secretary of the Party committee, Secretary of the Discipline Inspection Commission, part of the central ministries and state organs Department The first party committee is mainly responsible for people, views of experts and scholars and grassroots party organizations and Party members. Approved by the Central Committee of the Communist Party of China, on 7 September 2015, the general office of the Central Committee of the Party issued a notice to solicit the provinces (autonomous regions, municipalities) Party, the central ministries and commissions, state ministries and commissions of the Party (party), the General Political Department of the military, every 3 people organization of Party of two regulations revision opinion. Central Commission for Discipline Inspection of extensive solicitation of opinions, careful study, attracting, formed a revised sent reviewers. In October 8 and October 12, Central Committee Political 28 Bureau Standing Committee and the Political Bureau of the Central Committee After consideration of the two regulations revised draft. On October 18, the Central Committee of the Communist Party of China formally issued two regulations. Can say, two laws amendment concentrated the wisdom of the whole party, embodies the party. Second, < code > and < Regulations > revision of the basic principles of two party regulations revision work and implement the party's eighteen, ten eight plenary, the spirit of the Fourth Plenary Session of the Eleventh Central Committee and General Secretary Xi Jinping important instructions on the revised < low political criterion > and < Regulations >, highlighting the ruling party characteristics, serious discipline, the discipline quite in front of the law, based on the current, a long-term, advance as a whole, with Bu Xiuding independent < rule > and < rule >. Main principle is: first, adhere to the party constitution to follow. The constitution about discipline and self-discipline required specific, awaken the party constitution of party compasses party consciousness, maintaining the authority of the constitution. General Secretary Xi Jinping pointed out that "no rules, no side round. Party constitution is the fundamental law, the party must follow the general rules. In early 2015 held the eighth session of the Central Commission for Discipline Inspection Fifth Plenary Session of the 16th Central Committee, Xi Jinping again pointed out that constitution is the party must follow the general rules, but also the general rules." the revision 29 of the < code > and < rule > is Method in adhere to the regulations established for the purpose of combining rule of virtue is to adhere to the party constitution as a fundamental to follow, the constitution authority set up, wake up the party constitution and party rules the sense of discipline, the party constitution about discipline and self-discipline specific requirements. 4 second is to adhere to in accordance with the regulations governing the party and the party. The Party of rule of virtue "de", mainly refers to the party's ideals and beliefs, excellent traditional style. The revised the < code > closely linked to the "self-discipline", insisting on the positive initiative, for all members, highlight the "vital few", emphasized self-discipline, focusing on the morality, and the majority of Party members and the ideological and moral standards. The revised < > Ji method separately, Ji, Ji Yan to Method, as a "negative list", emphasizing the heteronomy, focusing on vertical gauge. Is this one high and one low, a positive reaction, the strict party discipline and practice results transformation for the integration of the whole party to observe moral and discipline requirements, for the majority of Party members and cadres provides benchmarking and ruler. Third, insist on to. In view of the problems existing in the party at the present stage, the main problems of Party members and cadres in the aspect of self-discipline and abide by the discipline to make clearly defined, especially the party's eighteen years strict political discipline and political rules, organization and discipline and 30 to implement the central eight provisions of the spirit against the four winds and other requirements into Disciplinary provisions. Not one pace reachs the designated position, focusing on in line with reality, pragmatic and effective. After the revision of major changes, major changes in the < code > and < rule > modified and needs to grasp several key problems (a) < code > < code > adhere to according to regulations governing the party and party with morals in combination, for at the present stage, the leadership of the party members and cadres and Party members in existing main problems of self-discipline, put forward principles, requirements and specifications, showing Communists noble moral pursuit, reflected at all times and in all over the world ethics from high from low 5 common requirements. One is closely linked to the "self-discipline", removal and no direct relation to the provisions of . the second is adhere to a positive advocate, "eight prohibition" 52 are not allowed to "about the content of the" negative list moved into synchronization amendment < cases >. Three is for all the party members, will apply object from the leadership of the party members and cadres to expand to all Party members, fully embodies the comprehensive strictly required. The fourth is prominent key minority, seize the leadership of the party members and cadres is the key, and put forward higher requirements than the ordinary Party members. Five is to simplify, and strive to achieve concise, easy to understand, easy to remember. The revised < code > is the ruling Party since the first insists on 31 a positive advocate forAll Party members and the self-discipline norms, moral declaration issued to all members of the party and the National People's solemn commitment. > < criterion of a clean and honest administration consists of 4 parts, 18, more than 3600 words. After the revision of the < code >, a total of eight, 281 words, including lead, specification and Party member cadre clean fingered self-discipline norms, etc. Part 3 members low-cost clean and self-discipline, the main contents can be summarized as "four must" "eight code". Lead part, reiterated on ideal and faith, fundamental purpose, the fine traditions and work style, noble sentiments, such as "four must" the principle of requirements, strong tone of self-discipline, The higher request for 6 and supervised tenet, the foothold in permanent Bao the party's advanced nature and purity, to reflect the revised standards requirements. Members of self-discipline norms around the party members how to correctly treat and deal with the "public and private", "cheap and rot" thrifty and extravagance "bitter music", put forward the "four norms". Party leader cadre clean fingered self-discipline norms for the leadership of the party members and cadres of the "vital few", around the "clean politics", from civil servant of the color, the exercise of power, moral integrity, a good family tradition and other aspects of the leadership of the party members and cadres of the "four norms" < > < norm norm. "The Party member's self-discipline norms" and "party members and leading cadre clean fingered self-discipline norms," a 32 total of eight, collectively referred to as the "eight". "Four must" and "eight" of the content from the party constitution and Party's several generation of leaders, especially Xi Jinping, general secretary of the important discussion, refer to the "three discipline and eight points for attention" statements, and reference some embody the Chinese nation excellent traditional culture essence of epigrams. (2) the revised regulations, the main changes in the revised Regulations > to fully adapt to the strictly requirements, reflects the according to the regulations governing the law of recognition of deepening, the realization of the discipline construction and Jin Ju. < rule > is party a ruler, members of the basic line and follow. And the majority of Party members and cadres of Party organizations at all levels should adhere to the bottom line of thinking, fear discipline, hold the bottom line, as a preventive measure, to keep the party's advanced nature and purity. 1, respect for the constitution, refinement and discipline. Revised < rule > from comprehensive comb physical constitution began, the party constitution and other regulations of the Party of Party organizations and Party discipline requirements refinement, clearly defined in violation of the party constitution will be in accordance with regulations to give the corresponding disciplinary action. The original 10 categories of misconduct, integration specification for political discipline, discipline, honesty and discipline masses Ji Law and discipline and discipline and other six categories, the content of < rule > 33 real return to Party discipline, for the majority of Party members and listed a "negative list. 7 2, highlighting the political discipline and political rules. > < Regulations according to the stage of the discipline of outstanding performance, emphasizing political discipline and political rules, organization and discipline, in opposition to the party's leadership and the party's basic theory, basic line, basic program and basic experience, the basic requirement of behavior made prescribed punishment, increase the cliques, against the organization such as violation of the provisions, to ensure that the central government decrees and the Party of centralized and unified. 3, adhere to strict discipline in the law and discipline In front, Ji separated. Revised < Regulations > adhere to the problem oriented, do Ji separated. Any national law existing content, will not repeat the provisions, the total removal of 79 and criminal law, repeat the content of the public security management punishment law, and other laws and regulations. In the general reiterated that party organizations and Party members must conscientiously accept the party's discipline, die van comply with national laws and regulations; at the same time, to investigate violations of Party members and even criminal behavior of Party discipline and responsibility, > < Regulations distinguish five different conditions, with special provisions were made provisions, so as to realize the connection of Party discipline and state law. 4, reflect Wind building and anti-corruption struggle of the latest achievements. < rule > the party's eighteen years 34 implement the spirit of the central provisions of the eight, against the requirements of the "four winds" and transformation for disciplinary provisions, reflecting the style construction is always on the road, not a gust of wind. In the fight against corruption out of new problems, increase the trading rights, the use of authority relatives profit and other disciplinary terms. Prominent discipline of the masses, the new against the interests of the masses and ignore the demands of the masses and other disciplinary terms and make provisions of the disposition and the destruction of the party's close ties with the masses. Discipline to protect the party's purpose. 8 of these regulations, a total of three series, Chapter 15, 178, more than 24000 words, after the revision of the regulations a total of 3 series, Chapter 11, 133, 17000 words, divided into "general" and "special provisions" and "Supplementary Provisions" Part 3. Among them, add, delete, modify the provisions of the proportion of up to nearly 90%. 1, the general general is divided into five chapters. The first chapter to the regulations of the guiding ideology, principles and scope of application of the provisions, highlight the strengthening of the party constitution consciousness, maintenance the authority of Party Constitution, increase the party organizations and Party members must abide by the party constitution, Yan Centralized centralized, would examine at all levels of the amended provisions implementing and maintaining Party discipline, and consciously accept the party discipline, 35 exemplary compliance with national laws and regulations. The second chapter of discipline concept, disciplinary action types and effects of the regulations, will be a serious warning from the original a year for a year and a half; increase the Party Congress representative, by leaving the party above (including leave probation) punishment, the party organization should be terminated its representative qualification provisions. The third chapter of the disciplinary rules of use prescribed in the discipline rectifying process, non convergence, not close hand classified as severely or heavier punishment. "Discipline straighten "At least eighteen years of five years, these five years is to pay close attention to the provisions of the central eight implementation and anti -" four winds ". The fourth chapter on suspicion of illegal party disciplinary distinguish five different conditions, with special provisions were made provisions, to achieve effective convergence of Party and country 9 method. < rule > the provisions of Article 27, Party organizations in the disciplinary review found that party members have committed embezzlement, bribery, dereliction of duty dereliction of duty and other criminal law act is suspected of committing a crime shall give cancel party posts, probation or expelled from the party. The second is < Regulations > Article 28 the provisions of Party organizations in the disciplinary review But found that party members are stipulated in the criminal law, although not involved in a crime shall be investigated for Party discipline and responsibility should 36 be depending on the specific circumstances shall be given a warning until expelled punishment. This situation and a difference is that the former regulation behavior has been suspected of a crime, the feeling is quite strict, and the latter for the behavior not involving crime, only the objective performance of the provisions of the criminal code of behavior, but the plot is a crime to slightly. < Regulations > the 29 provisions, Party organizations in the discipline review found that party members and other illegal behavior, affect the party's image, the damage to the party, the state and the people's interests, we should depend on the situation Seriousness given disciplinary action. The loss of Party members, seriously damaging the party's image of behavior, should be given expelled from the party. At this article is party member is in violation of the criminal law outside the other illegal acts, such as violates the public security administration punishment law, customs law, financial laws and regulations behavior. The fourth is < cases > Article 32 stipulates, minor party members and the circumstances of the crime, the people's Procuratorate shall make a decision not to initiate a prosecution, or the people's court shall make a conviction and exempted from criminal punishment shall be given within the party is removed from his post, probation or expelled from the party. Party members and crime, sheets were fined in accordance with For acts; the principal Ordinance amended the provisions of the preceding paragraph. This is the new content, in order to achieve Ji method effective 37 convergence. Five is < > the thirty third article 10 of the provisions, the Party member due to an intentional crime is sentenced to criminal law (including probation) sheets or additional deprivation of political rights; due to negligence crime and was sentenced to three years or more (excluding three years) a penalty, shall give expelled punishment. Due to negligence crime is convicted and sentenced to three years (including three years) in prison or be sentenced to public surveillance, detention, shall in general be expelled from the party. For the individual may not be expelled from the party, should control Approval. This is followed and retained the original > < Regulations the provisions of punishment party authorization rules and report to a level party organizations. For is "party members with criminal acts, and by the criminal punishment, generally should be expelled from the party". The fifth chapter of probationary Party member of the discipline and discipline after missing members of the treatment and punishment decisions, such as the implementation of the provisions, clear the related party discipline and punishment decision made after, for duties, wages and other relevant alteration formalities for the longest time. 2, sub sub section will the original regulations of 10 categories of acts of violation of discipline integration revised into 6 categories, respectively, in violation of the punishments for acts of political discipline "in violation of discipline behavior of punishment" in violation of integrity of disciplinary action points "of violation punishments for acts 38 of mass discipline" "the violation of work discipline, punishment" in violation of discipline of life behavior punishment "6 chapters. 3, annex" Supplementary Provisions "clear authority making supplementary provisions of, cases of interpretative organ, as well as regulations implementation time and retroactivity etc.. 11 (3) learning understanding > < regulations needs to grasp several key problems The first problem -- about the violation of political discipline behavior > < new ordinance chapter 6 the political discipline column for the six disciplines, that is the main opposition to Party leadership and the opposition of the basic theory, basic line, basic program and basic experience, basic requirements of misconduct made provisions of the disposition, especially the eighteen since the CPC Central Committee put forward the Yan Mingzheng treatment of discipline and political rules requirements and practical achievements transformation for Discipline article, increase the false debate central policies, cliques, against the organization review, make no discipline of the principle of harmony terms. These are the party's eighteen years in comprehensive strictly Process combined with the practice of rich content. (1) false debate the central policies and undermine the Party of centralized and unified the problem is made in accordance with the provisions of the party constitution. Constitution in general programme requirements adhere to democratic centralism is one of the requirements of the construction of the party must adhere to the four cardinal. Application 39 of this principle is not only the party the basic organization principle and is also the mass line in party life, it requires that we must fully develop inner-party democracy, respect for the dominant position of Party members, safeguarding the Party member democratic rights, give full play to the enthusiasm and creativity of the party organizations at all levels and Party members, at the same time, also must implement the right concentration, ensure the party's mission < the chaos in unity and concerted action to ensure that the party's decision to get quickly and effectively implementing. The Party Central Committee formulated the major principles and policies, through different channels and ways, fully listen to the party organizations and Party members of the opinions and suggestions, but 12 is some people face to face not to say back blather "" will not say, after the meeting said, "" Taiwan does not say, and nonsense ", in fact, not only disrupt the people thought, some causing serious consequences, the damage to the Party of the centralized and unified, hinder the central policy implementation, but also a serious violation of the democratic system of principles. There is no doubt that shall, in accordance with the Regulations > 4 Specified in Article 6 to give the appropriate punishment. For did not cause serious consequences, to give criticism and education or the corresponding tissue processing. (2) about the destruction of the party's unity < New Regulations > the forty eighth to fifty second article, to damage Party's unity unified and violation of political discipline, punishment situation 40 made explicit provisions. Article 52 of the new "in the party get round group, gangs seek private gain, cliques, cultivate private forces or through the exchange of interests, for their own to create momentum and other activities to gain political capital, given a serious warning or withdraw from their party posts disposition; if the circumstances are serious, to give Leave a party to observation or expelled from the party. (3) on against the organization review of the provisions of the constitution, party loyalty honesty is party members must comply with the obligations. Members must obey the organization decision, shall not violate the organization decided encounters by asking questions to find organization, rely on the organization, shall not deceive the organization, against the organization. For example, after the investigation does not take the initiative to explain the situation, but to engage in offensive and defensive alliance, hiding the stolen money is against survey organization, is a violation of the behavior of political discipline. Article 24 of the original > < Regulations, although the provisions of the interference, hinder group review the behavior of the fabric can be severely or 13 Aggravated punishment, but did not put this kind of behavior alone as a discipline for qualitative amount of discipline. > < new regulations increase the Article 57, "anti organization review, one of the following acts, given a warning or serious warning; if the circumstances are relatively serious, giving removed from or placed on probation within the party post; if the circumstances are serious, give 41 expelled from the party: (a) on supply or forged, destroyed, transfer, conceal evidence; (II) to prevent others expose, providing evidence Material; (III) harboring co personnel; (4) to the organization to provide false information, to hide the fact; (5) the him against the acts of the organization review. "< rule > add this clause to the Constitution requires more specific, the previous no punishment in accordance with the definite list and put forward clear punishment in accordance with. (4) about organizing or participating in superstitious activities as < Regulations > about engage in activities of feudal superstition obstruction of social management order" violations of Article 164 the provisions, but according to the original < rule > only in disrupting production, work, social life order The case to be disciplinary treatment, in other words, alone make the feudal superstition, organize or participate in the activities of feudal superstition of, does not constitute a violation. Which is not consistent with the requirements of our party's political party. > < new regulations in this change is, superstitious activities on the political discipline, increase the Article 58, is the organization of Party members, in superstitious activities included in violation of the negative list of political discipline deserves punishment, which and Party members should adhere to the correct political principle, political standpoint and viewpoint is consistent. 14 the second question about organization and discipline violation behavior of democratic centralism is our The party's fundamental 42 organizational system. < New Regulations > Chapter 7 "in violation of the behavior of organizational discipline punishment" mainly for violation of democratic centralism, contrary to the "four obey the discipline behavior for source classification rules. Increased not in accordance with the relevant provisions or requirements to the organization for instructions to report on major issues; do not report truthfully report about personal matters; falsify personal archives; hide before joining the party serious mistakes; leading cadres in violation of the relevant provisions of the organization, will participate in the spontaneous formation of the old Xiang, Alumni Association, comrades in arms; to obtain illegal country residence abroad or foreign nationality, illegal for private frontier Documents such as discipline terms. (1) on the report truthfully report personal matters in 2010 the Central Committee of the Communist Party of China office, office of the State Council introduced < provisions on issues related to the leading cadres to report personal >, is clear about the request, deputy division level and above leading cadres should truthfully report changes in my marriage and spouse, children, moved to the country (territory), practitioners, income, real estate, investment and other matters, for failing to report, do not report, concealed and unreported, according to the seriousness of the case, giving criticism and education, and to make a correction within a time limit, shall be ordered to make a check, the commandment Jiemian conversation, informed criticism or jobs, free Post 43 processing, constitute violations, in accordance with the relevant provisions shall be given a disciplinary sanction. But since the original < Regulations > and there is no corresponding specific terms, the violation of the regulations, do not report, as a false report about personal matters, there is no corresponding disciplinary action terms, in practice it is difficult to operate. In this regard, in order to solve is not reported, as a false report about personal matters 15 asked censure, the new < Regulations > add the Article 67 of violation of personal matters related to reporting requirements, report truthfully report the clear punishment basis, making this kind of violation behavior is no longer free drilling for Exhibition on matters of personal checks to verify and supervision of cadres, discipline review provides a powerful discipline guarantee. (2) about the illegal organization, to fellow, alumni, friends of the war will < regulations stipulated in Article 68 of >, leading cadres of the party in violation of relevant provisions of the organization, will participate in the spontaneous formation of fellow, Alumni Association, comrade in arms to give the punishment according to the seriousness of the case. Here special needs note is three points: this provision for only the leading cadres ", reflecting the high requirements of leading cadres; second violation in 2002, the Central Commission for Discipline Inspection, the central Organization Department and the The relevant provisions of the General Political Department jointly issued the < off in leading cadres not to participate in 44 the initiative to set up "the villagers would be" alumni "" comrades in arms organization notice >. That is to say, to the spontaneous formation of fellow, Alumni Association, comrades in arms will constitute the premise of discipline is a violation of the provisions of this. The notification specified, leading cadres are not allowed to participate in the spontaneous incorporation of fellow, alumni, between comrades association would like the organization and shall not bear the sorority Human and the organizer shall not hold the corresponding position in the sorority; shall not borrow machine woven "network" and engage in kiss sparsely, round and round the gangs, but not "align" "Jieyi Gold Orchid" behavior. The third is to emphasize here that shall be organized to participate in the initiative to set up the villager, Alumni Association, comrades in arms. The so-called 16 spontaneous was established mainly means without registration. Therefore, Party members include leading cadres in the normal range of fellow, alumni, comrades in the party is not a violation of the rules of Party discipline. The three problem about integrity violations discipline Lian Jie discipline has been eighteen years clean government and anti The focus of the work of corruption. This Ordinance to amend, honesty and discipline this biggest adjustment, the new content, most of which prescribed by the original < criterion of a clean and honest administration > 8 ban and 52 are not allowed into the basic this part. (1) the central eight provisions of the spirit and requirements into < New > in 45 the regulations of the party's eighteen years, central resolutely implement the provisions of the eight and pay close attention to the node and intensive briefing, on public funds, private bus, public funds tourism, gifts of public funds, the big parade and lavish weddings and festive, illegal payment allowances and subsidies, illegal construction of buildings such as the original masses reflects the relatively strong, "four winds" problem of the Resolute rectification. But original < Regulations > to eat and drink, super standard reception and no clear and specific expression, new < rule > will implement eight Central provisions of the spirit of the problem increased to "clean cheap self-discipline" chapter, clear to exceed the standard, beyond the scope of the reception or borrow machine eating and drinking etc. some in violation of the provisions of the spirit of the eight central relevant persons responsible for punishment, once the violation will be according to the < rule > severely punished, binding, enhanced significantly. One is to add Article 87, about to obtain illegal, hold, and the actual use of the sports card, golf ball cards and other consumer card. Illegal access to private clubs made the punishment provisions. The second is increase the Article 97, has made provisions of the disposition of illegal self pay or 17 spamming allowances, subsidies and bonuses. The third is added to the Article 99, on violation of super standard, beyond the scope of the reception or borrow machine eat and drink to make the provisions of punishment. The fourth is to increase the Article 101, on the management 46 of conference activities in violation of the provisions made sanctions regulations. The fifth is the increased Article 102, for violation of office space management provisions made the punishment provisions. Six is to split the original < rule > Article 78, formed article 98, Article 100 of public Models of tourism, violate the provisions on the administration of the use of discipline of the bus through the list of made a more detailed provisions, apply more operational. Seven is increased the article 96, in violation of the relevant provisions of the, to participate in public funds to pay for dinner, high consumption of entertainment, fitness activities and public funds to buy gift, send gifts to make the provisions of the disposition. On the violation of the central provisions of the spirit of the eight, in addition to > < new regulations into "violation of honesty and self-discipline" misconduct outside, is different with the original < Regulations >, revised < rule > clearly defined not only to disposition of the directly responsible persons, but also dispose of collar Guide responsibilities. (2) increased trading rights, use of authority or position influence as relatives and close to profit violation of the terms of the < New Regulations > absorption < clean politics several guidelines > the relevant provisions spirit, increase the "negative list, including trading rights, the functions and powers or duties of influence as relatives and staff around profit. Increase Article 81" mutual use of office or authority ring for each other and their spouses, children and their spouses and other relatives, 47 around 18 personnel and other specific relationship between the people to seek benefits engage in trading rights, given a warning or serious warning Sanctions; if the circumstances are relatively serious, giving removed from or placed on probation within the party post; if the circumstances are serious, shall be expelled from the party. Increase Article 82 "connivance, acquiescence to the spouse, children and spouse etc. relatives and staff around the effect of Party members and cadres personal authority or position for personal gain, if the circumstances are relatively minor, given a warning or a serious warning; if the circumstances are relatively serious, giving removed from or placed on probation within the party post; if the circumstances are serious, the given Expelled from the party. Party members and cadres of the spouses, children and their spouses does the actual work and get salary or although the actual work but to receive significantly beyond the same rank salary standard, Party members and cadres informed fails to correct, in accordance with the provisions of the preceding paragraph. "(3) about the gifts, gifts misconduct from handling practices in recent years, engaged in official cadres received gifts, gifts problems more prominent. This has seriously affected the image of Party members and cadres, damaged the relations between the party and the masses, and is a hotbed of corruption, is really necessary for this kind of behavior to be disciplined. < rule > no on accepting gifts, gifts, Card consumption behavior to engage in simple "one 48 size fits all", but the difference between the different separately. One is in accordance with the provisions of Article 83, accepting may affect the impartial enforcement of the official gifts, gifts, consumer cards to depending on the seriousness of the case shall be given disciplinary sanctions. That is to say, for may affect the fair execution of business gifts, gifts, consumer cards are not allowed to accept. 19 is in accordance with the provisions of Article 83, accepting was significantly higher than normal ceremony is still exchanges of gifts, gifts, consumer card to disciplinary action. This is new regulations that daily life is purely reciprocity, accepting the same thing, boys , fellow friends gifts, gifts, shopping cards, although and fair execution of business has nothing to do, also want to as the case shall be dealt with, the situation is obviously beyond normal reciprocity ". The so-called" reciprocity ", one is emphasizes the reciprocal in protocol. In other words is you to me how, I to you how, not only does not go. The second is to significantly exceeded the normal local economy level, customs and habits, economic capacity of individual gifts, gift value. Specific sanctions to according to the processing of a variety of factors to consider, as appropriate. The third is the root according to the provisions of Article 84," to Engaged in public service personnel and their spouses and children, children's spouses and other relatives and other specific relationship presented Ming Xianchao normal reciprocity of gifts, gifts, consumer card, if the circumstances are 49 relatively serious, given a warning until probation. "In accordance with the above provisions, gift giving significantly beyond the normal reciprocity, giver constitute the discipline. (4) on illegal trading of stocks or of other regulations of securities investment < > Article 88 is engaged in punishment regulation of camp and activity in violation of the relevant provisions on. Among them, 3 will" buying and selling stocks or in other securities investment "column as one of disciplinary cases Out. First need to be clear, > < regulations did not change the provisions of the Ordinance. The ordinance of the provisions of the second paragraph of Article 77 provisions "who, in violation of the provisions of the sale of stocks" is one of the violation, and at the beginning of the first paragraph of this article "violation of 20 against the relevant provisions of the" textual representation of the repeat revision. In, just from the legislative technique removed the "personal" in violation of the provisions, content and not to change the original provisions. Need to clear is, "buy or sell a stock or of other securities investment" refers to violation of the relevant provisions refers to in April 2001, the Party Central Committee, the State Council promulgated the On the work of the party and government organs staff's personal investment in securities if dry provisions >. According to the provisions of Article 3, use of work time, office facilities, the sale of stocks and securities investment fund belongs to illegal behavior. The fourth question, about the violation of the masses of the disciplinary actions < 50 new regulations > would violate public discipline behavior of a single set of a class of restored "three rules of discipline and eight note" in the discipline of the masses of excellent traditional. < New Regulations > Chapter 9 "to violate the masses of disciplinary action", mainly the destruction of the party's close ties with the masses of misconduct made provisions on disciplinary; enrich and perfect the super standard, beyond the scope of Xiang Qun < All to raise fund and labor, in for involving the public affairs deliberately, chinakayao, in social security, policy support, disaster relief funds and materials and other matters assigned any kind and affectionate friends, obviously unfair acts against the interests of the masses of the disciplinary terms; increase the terms not in accordance with the provisions of the public party provided, government, factory and village (neighborhood) provided etc. violation of the people's right to know the behavior of the discipline. The fifth issue, on the violation of work discipline violation of work discipline added "negative list, including Party organizations carry out strictly Main responsibility for poor discipline terms. (1) the new party organization comprehensive strictly the main responsibility of the party does not fulfill the 21 or perform poor disciplinary terms < New Regulations > has a lead people to pay attention to the new terms, that is, in chapter ten "on the violation of work discipline behavior punishment" increase in the one hundred and fourteenth "party fail to perform 51 comprehensive strictly the main responsibility of the party or to perform comprehensive strictly the main responsibility for administering the ineffective, resulting in serious damage or serious adverse effects, to the person directly responsible and the responsibility of leadership and give a warning or serious warning. The situation is serious, giving removed from their party posts or on probation Punishment. "Here the changes. For the first time, the main responsibility write < rule >. (2) new shall report does not report or false reporting discipline shall increase the 117 bar" in the higher level units to check to inspect the work or report to the parent unit, work report of shall report the matters do not report or do not report, cause serious damage or serious adverse effects of, to the person directly responsible and the responsibility of leadership, to give warning or a serious warning; if the circumstances are serious, giving removed from their party posts or placed on probation. "For example, during the tour visits to the region, the unit Members the obligation to the inspection teams to reflect the true situation, to conceal not reported or intentionally to the inspection teams to provide false information, causing serious damage or serious adverse effects of, the person directly responsible and the responsibility of leadership should be in accordance with the provisions of < rule > Article 117 to give the appropriate punishment. (3) the new not granted in accordance with the provisions of punishment, not according to the provisions of the implementation of disciplinary measures 22 violation 52 of the provisions of Article 115 "Party organizations have one of the following circumstances, the direct leadership responsibility. Probation: members were sentenced punished, in accordance with the provisions give disciplinary action or in violation of state law Rules of behavior should be given disciplinary punishment and dispose of; disciplinary punishment by decision or complaint review the decision made, not in accordance with the provisions of the implementation decisions on punishment of the party, position, rank, and the treatment of the matters; Party members subject to disciplinary action, not in accordance with the cadre management authority and organizational relationships of by dispose of Party members to carry out education and supervision of daily management. "What needs to be pointed out is," cliff "demoted with cars, housing, secretary problem, implementation is not a discipline and party posts and ranks treatment by the organization department is responsible for the implementation, with cars, housing by the logistics department is responsible for the implementation of, Ji Commission responsible oversight responsibilities. The six questions, about the acts violating the discipline of life "in violation of discipline of life behavior punishment", mainly to "four winds" problems and a serious violation of social morality, family virtue acts of misconduct made provisions on disciplinary, an increase of extravagant life, contrary to the social public order and good customs disciplinary terms. Worth mentioning is, > < Regulations in Article 150 53 about "adultery" "mistress (Cardiff) formulation in the new < rule > is removed, to expand the scope of Article 127 provisions" and others hair improper sexual relations, let face disciplinary action Wider more strict. Four, and earnestly do a good job in the < code > and < rule > implement system of life lies in execution. < code > and < Regulations > is 23 Party organizations at all levels of a strong constraint and all Party members follow. Learning and implementing the < code > and < rule > is party committees (party), commission for discipline, discipline inspection group), the majority of Party members and cadres of the common responsibility, must party caught together, the party one execution. () Party committees (party) and play and implement comprehensive strictly the main responsibility, pays special attention to the two party regulations learning cross penetration. One is to Adhere to the party constitution is fundamental to follow, and resolutely safeguard the authority of the Party Chapter. The second is to adhere to the problem oriented, to strictly political discipline and political rule moments in the first place. The third is to adhere to the discipline and rules quite in front must not allow the bottom line to break the discipline. The fourth is to seriously organize the study of propaganda and education, in the city party members to create a disciplined, about the rules of the strong atmosphere. (II) Commission for Discipline Inspection at all levels (Discipline Inspection Group) to an important basis for the revised two party regulations as, adhere to easily 54 blame, strengthen supervision and enforcement And early method in combining Ji, increase accountability efforts. One is to two regulations within the party important basis, adhere to the party constitution duties, with strict discipline to maintain the constitution authority. The second is to adhere to high standards and keep the bottom line, adhere to Ji Yan in law and discipline, the discipline and rules quite in front, grasping grasping small, easily blame, comprehensive use of supervision and discipline of "four kinds of form" in the discipline embodies the strict requirements and care for the discipline, tighten up, Yan. According to discipline in accordance with regulations to carry out disciplinary review. Increase the violations punishment, clues can initiate an investigation on the trial of cases According to the discipline on the provisions of the proportion of processing and control manager maintains discipline. To focus on investigating non convergence, don't accept hand serious disciplinary violations at the same time, pay more attention to the general review of discipline 24 behavior, and gradually increase the lighter punishment. Four is to illuminate two party regulations, combined with the local district of the Department of party conduct Lianzheng to relevant laws and regulations system clean, timely research proposes to establish, change, waste release opinion, avoid conflict, and the fasten system of cage, and gradually formed not rot, not rot, not want to rot system and working mechanism. (3) the leadership of the party members and cadres 55 should play an exemplary role. The rate of higher consciousness of the front of the Ordinance to lead practice self-discipline norms, leading to maintain discipline of seriousness and authority. One is the above rate, demonstration and guidance, take the lead in learning and mastering the < code > and < > the requirements and regulations, do the deep understanding, learning to use. The second is to play an exemplary role in abiding by discipline rate, take the lead in practicing self-discipline norms, firmly establish before the discipline are equal, the system has no privilege, discipline is no exception, and consciously do standards, require more strict measures more practical. Third is to consciously accept supervision, conscientiously participate in the democratic life and debriefing honesty responsibility, such as Real to the party organization to report personal matters, and to accept the supervision of the work and life of the normal, habits under the supervision of the exercise of power, to carry out the work. The fourth is to set an example for the strict enforcement of discipline. Leading cadres should take the lead in the maintenance of discipline of seriousness and authority, to dare to seriously, dare to struggle, dare to offend people, for misconduct not laissez faire, but do not indulge, not tolerate to ensure the party constitution of party compasses party put in place. (4) the majority of Party members and cadres to set high standards and hold the bottom line, consciously abide by the < code > and < rule >. One is to control the < standard > and < 25 cases >, tight Close connection 56 with their own thoughts, practical work and life, efforts to solve the problems, to enhance the study and implement of the effectiveness and pertinence. The second is to establish a high standard and hold the bottom line, consciously in the self-discipline pursuit of high standards, strictly in the party away from the red line discipline, discipline, about the rules and know fear, distrust, the formation of the honor system, comply with the system, safeguard system of good habits. Regulations and discipline regulations of < < New Revision of the Communist Party of China clean fingered self-discipline criterion > and < Chinese Communist Party Disciplinary Regulations > is the Party Central Committee in the new situation to promote the comprehensive strictly root of the lift, the regulations of the party construction of keeping pace with the times. We should study and implement the Standards > and < > as the primary political task, adhere to the party constitution duties, adhere to the discipline of, Ji Yan in law, the full implementation of supervision and discipline accountability responsibilities for coordination and promotion "four overall" strategic layout in XX District vivid practice to provide a strong guarantee. - Si Jian Wu, and effectively enhance the implementation of the implementation of the < code > < > The consciousness of General Secretary Xi pointed out that the party is in charge of the party, to manage the party; strictly, it can cure good party. Criterion > and < rule > keep pace 57 with the times is our party to form a new potential strictly rules, to deepen understanding of the ruling law, is a comprehensive strictly, and strengthen the supervision within the party important grasper. Criterion > closely linked to the theme of self-discipline, self-discipline intensity-modulated, focusing on morality, for the majority of Party members and cadres set to see, feel the high standard, show the Communists noble moral sentiment; District Ordinance < < rule > the constitution of discipline integration into a political discipline, organization and discipline, honesty and discipline, discipline of the masses, work discipline, discipline, emphasize discipline, focusing on established rules, to draw the party organizations and Party members do not touch the bottom line. Party committees (party) to effectively strengthen the study and publicize the implementation of the < code > and < rule > the organization and leadership of criterion > and < > a full range, multi angle, deep publicity, the formation of study and publicize and implement the boom, in order to consolidate the development of good political environment to create a positive environment and atmosphere. The majority of Party members and cadres to strict requirements, the < rule > and < Ordinance cases > as a guide to action and behavior criterion, adhere to the moral standards and discipline of the bottom line, to maintain the discipline of worship and awe, learning, compliance, and maintain party discipline and rules of the model. The discipline inspection and supervision organs and cadres to the < code > and < > as the deepening of 58 the "three", and strengthen supervision and discipline of accountability is important to follow correctly grasp the use of supervision and discipline of "four types", promote the comprehensive strictly in new roots. Strict discipline, adhere to the discipline and rules quite in front of the enterprise in the implementation of expensive to implement to execute. The discipline inspection and supervision organs to implement the < code > and < Efforts to investigate cases > as an opportunity, adhere to the party should manage the party strictly, serious performance of their duties to promote two regulations implementation. Change discipline concept. From the simple "investigation of illegal" to a comprehensive "stare at violate discipline"; from the business case to prosecute the big cases and timely solve the signs of tilt to. From the orientation to the normal supervision; from the tube "minority" to resist the "most". Guide Party members and cadres to seriously implement the < code > and < rule >, consciously abide by the political, organizational, honest people, work, life six discipline. Urge the leadership cadres sent to play an exemplary role, take the lead in strictly enforced. Relaxation and rest Strong wind is Su Ji, closely linked to the "four winds" prone to multiple, the masses reflect the strong important nodes and, glued to the four winds "new form, new trends, seriously investigate and deal with violations of the central eight provisions of the spirit, to increase the bulletin exposure intensity, the formation of Chajiu" four winds "loudly, continue to release and discipline 59 must be strict signal. At the same time, extended supervision tentacles, through the development of the rural and fishery party conduct Lianzheng construction inspection, issued in a timely manner, Chajiu occurred in grassroots side of corruption and unhealthy, and earnestly safeguard the interests of the masses and social stability. The creativity and discipline. Grasp and make good use of the supervision and discipline of" four types ", to ensure the Promoting clues to lots of discipline and the law of the vacuum tube, strict together. Not only to the "less" and "very few" thorough investigation severely punished, but also the "most" to maintain zero tolerance trend through layers of conductive pressure, let the discipline about the rules for each party members and cadres consciously follow. At present, it is necessary to implement the "list" management, strictly follow the clues to the disposal of five standards, make the classification of disposal, dynamic cleanup. Zadok Party committees at all levels to implement the main responsibility, comprehensive use of disciplinary action and tissue processing and other means to effectively curb the commonplace, used to see do not blame the "small problem", not because of "practice" and "exception". Prominent Discipline characteristics, the problems of violation of discipline and rules into the focus of supervision and discipline and disciplinary review. At the same time, increase case double check the intensity, the serious problems of discipline violations or "four winds" ban but not absolutely, not only to be 60 held directly responsible, but also held leadership responsibility; not only to pursue studies the main responsibility of the Party committee, and to pursue Commission for Discipline Inspection and supervision responsibilities and promote accountability to become the new norm. The implementation of supervisory responsibility. Maintain < code > and < rule > the seriousness and authority of the discipline and rules and truly become the party's ruler. Discipline as supervision within the party the specialized agency, we must strengthen the responsibility to act, adhere to the Impartial discipline accountability, earnestly will be strict discipline, discipline must be punished, and severely punish the acts in violation of rules and regulations. 61