WCC * 9 Production and post-production information The manufacturer shall establish, document and maintain a system to collect and review information in the production and the post-production phases to evaluate 制造商应建立和保持一个收集包括同类产品的生产和上市后信息的系统，并形成文件，用于确定: a) if previously unrecognized hazards are present;是否有未识别的风险？b) if the estimated risk(s) arising from a hazard is no longer acceptable; 以前评价的风险是否不再可以接受？c) if the original assessment is otherwise invalidated. 是否最初的评定不再有效The manufacturer should consider the mechanisms by which information collected and processed; 制造商应考虑信息收集和加工的方法The manufacturer should also consider new or revised standards. 标准的更新也需要考虑风险再评价，why ？风险识别不完全临床暴露，如多支架使用；风险估计不准确S/P/D, 高估，成本增加，低估，风险失控；设计更改，更改对器械整体性能的影响法规的变更，如对关节、支架和起搏器等植入器械的追溯性法规。End of part A * WCC * How to find the hazards? 如何识别危害Sources to find hazard 识别危害的资料包括: 1. Standards 相关标准，如ISO 10555 －1 对导管的断裂力有详细规定2. Existing risk analyses of similar products 类似产品的风险分析3. Interviews with the design engineers 从设计工程师处获得信息4. Interviews with users of similar products 从器械的使用者处获得信息5. Experience of the sales people 销售人员的经验6. Brainstorming in Risk Assessment team 风险管理团队的头脑风暴活动7. Analysis of government Incident Reports 分析政府的事故报告8. Examination of existing risk mitigation measures; 检验风险控制措施9. Information from the field for similar products, e.g. complaints, incidents 相似产品的信息，如顾客抱怨，事故等……………WCC * Identification of hazards 危害识别Annex E ：Examples of hazards 附录E 中的危害举例Energy 能量危害biological and Chemical 生物和化学危害operational 操作危害information 信息危害Electromagnetic energy (Leakage current) 漏电Radiation energy Thermal energy (High temperature Low temperature) Mechanical energy (Moving parts) Biological (Bacteria cross-infection) 细菌交叉感染Chemical (Residues solution) Biocompatibility (Toxicity of chemical agent) Function (inappropriate Output) 不正确的输出Use error (reuse of disposable MD) Labelling (Incomplete instructions) 不充分的说明Operating instructions (Over-complicated) Warnings (side effects) Specification of service and maintenance 例：他山之石——著名的支架招回事件球囊导管组装过程：前后部连接——点胶过程——胶水过多——形成活塞效应；扩张时：压力泵——9atm 正压——球囊充盈——造影液回抽——1atm 负压——不能回抽——持续阻断血管——心肌缺血——心梗——死亡；了解器械的工作原理和临床使用，分析同类产品的事故原因，针对性采取措施，防止自己器械发生类似事故点胶激光焊接例：采购过程中的风险例：齐二药事件，肝素纳事件DMR 文件中是否规定：原材料清单合格供方清单采购质量标准检验规程抽样方法……? WCC * 4.4 Estimating the result 评估危害的后果what harm can result from hazards? 危害能导致什么伤害？例: 评估危害的结果封堵器NiTi 丝编制丝材表面缺陷损伤——电化学腐蚀——断裂——房颤——死亡表面缺陷：原材料，原材料进货检验加工过程中损伤，过程检验/ 成品检验2. 能量危害：UV 灯消毒，光老化( 化学) ：可吸收缝线降解药物降解球囊耐压降低生产过程中的产品防护WCC * What is the risk? 风险的概念风险：损害的严重程度和发生概率的结合；WCC * Relationship of risk, harm and hazard 危害、危害处境和风险的关系：注射器中进入了昆虫的可能性P1=0.0001 使用时护士未发现注射器中有昆虫的可能性P2=0.00001 护士使用有昆虫的注射器进行注射的可能性P ＝P1 xP2=0.000000001 十亿分子一WCC * Probability of harm 损害的可能性Probability 根据贵公司的产品属性来确定日产500 万支注射器的企业和年产1 万套起搏器的企业对“Probability ”的定义是不同的。WCC * How to quantify/qualify probability? 以下方法可以用于伤害发生概率的定量或定性：use of relevant historical data 使用相关的历史数据prediction of probabilities using analytical or simulation 用数学模拟和数据分析来预测可能性techniques (often very complex) 技术文件use of expert judgment 专家的判断请记住：贵公司的产品属性！WCC * Severity of harm 伤害的严重性Severity 应考虑贵公司的风险可接受方针，如带X －ray 纱布球显影性差即可定义为灾难性，尽管不会导致死亡。WCC * 4.4 risk estimation 风险估计Qualitative / Quantitative risk estimation WCC * 5 Risk evaluation 风险评价For each identified hazardous situation, the manufacturer shall decide, using the criteria defined in the risk management plan, whether or not the estimated risk is so low that risk reduction need not be pursued. 对每一种危害情况，制造商应该根据风险管理计划中的接受标准，判定风险是否需要控制。Records shall be taken. 保留相关的记录WCC * 5 Risk evaluation: acceptable or not? decide based on the criteria defined in the risk management plan, WCC * 5 Risk evaluation 风险评价Take into account of “As-low-as-reasonably-practicable ”approach 新标准在附录D 中保留了合理可接受(ALARP) 准则WCC * risk analysis techniques 风险分析技术Preliminary Hazard Analysis (PHA) 基本危害分析——Top to Down Fault Tree Analysis (FTA) 故障树分析——Top to Down Failure Mode and Effects Analysis (FMEA) 故障模式和效应分析For complex device system , FMEA is very useful in designing (DFMEA) and product controlling (PFMEA).——Down to Top Hazard and Operability Study (HAZOP) 危害及可操作性分析Hazard Analysis and Critical Control Point (HACCP) 危害分析和关键控制点附录G 中提到的一些风险分析技术WCC * 6 Risk control 风险控制6.1 Risk reduction 降低风险When risk reduction is required, the manufacturer shall take measure to control the risk so that the residual risk is judged acceptable. 6.2 Risk control option analysis 风险控制方法分析The manufacturer shall identify risk control measure that are appropriate for reducing the risk to an acceptable level. One or more of the following shall be used in the priority order listed: a) inherent safety by design; 安全设计——如单向接头b) protective measures in the medical device itself or in the manufacturing process; 器械自身具有的保护措施——如报警系统c) information for safety. 安全信息——警告WCC * inherent safety by design 安全设计产品质量是检验出来的吗？产品质量是生产出来的吗？产品质量是设计出来的吗？更进一步，产品质量是策划出来的吗？例：设计时使用成熟的医用材料确保医疗器械生物相容性，自毁式注射器安全结构设计防止重复使用; WCC * Option analysis 控制措施的选择You can reduce the risk by: 可以通过控制如下措施first choice: inherent safety by design 首先选择安全的设计second choice: protective measures in the medical device itself or in the manufacturing process 其次选择器械的保护措施third choice: information for safety 最后选择安全信息的公告注：多管齐下更好！WCC * 6.3 Implementation of risk control measure The manufacturer shall implement the risk control measure selected. The measure used to control the risks shall be recorded in the risk management file. 制造商应实施所选择的风险控制措施。用于控制风险的措施应记入风险管理文档1. Implementation of the risk control measures shall be verified. This verification shall also be recorded in the risk management file. 风险控制措施的实施应予以证实，证据应记入风险管理文档。2.The effectiveness of the risk control measures shall be verified and the results of the verification shall be recorded in the risk management file. 风险控制措施的有效性应得到验证，并且，验证结果应记入风险管理文档。WCC * examples of risk control measures risk control measures 风险控制措施实例WCC * checking the effectiveness 检验风险控制效果The effectiveness shall be verified by comparing the risks before and after the risk control measures taken. 比较控制前后的风险等级Severity Severity 1 2 3 4 1 2 3 4 6 6 5 R8 5 probability 4 4 3 3 2 2 R8 1 1 WCC * 6.4 Residual risk evaluation 剩余风险评估Any residual risk that remains after the risk control measure are applied shall be evaluated using the criteria defined in the risk management plan. The results of this evaluation shall be recorded in the risk management file. 在采取风险控制措施后遗留的任何剩余风险，都应使用风险管理计划中规定的准则进行评价。评价结果应记入风险管理文档。If the residual risk does not meet these criteria, further risk control measures shall be applied! 如果剩余风险不符合接受准则要求，应采取进一步的风险控制措施If the residual risk is acceptable, the information to explain the residual risk shall be record. 如果剩余风险被认为是可接受的，则所