FDA产品质量的风险评估原则(翻译)

,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,1,基于产品质量的风险评估原则,H.Gregg Claycamp,Ph.D.,CHP,Center for Veterinary Medicine,Office of New Animal Drug Evaluation,hclaycamcvm.fda.gov,June 25,2003,2,提纲,总前提和问题,风险分析的基本要素,实施,PQ,的风险评估的可能阶段,实施的风险分级模式,?,中试放大,结论,The opinions and ideas presented here are those of the author and do not represent policy or opinion of the FDA.This material is intended for discussion purposes only.,3,前提,:,工艺中的风险和患者的风险的联系已丢失,.,风险,工艺检查风险,cGMP,风险,质量,(,患者,),因素,患者,相互关系,?,模型,?,4,目标,:,重新将,cGMP(PQ),风险和对患者的实际风险联系起来,风险,工艺检查中的风险,风险,质量,(,患者,),因素,cGMP,患者,5,问题,Can,Risk Management,theory,tools,practice and philosophy be employed to re-link risks to the patient with the risks identified,perceived or otherwise implicated in product quality terms?,风险管理理论,工具,实践和哲学,How can we share a common language about risk,risk management,and science-based decision making so that we can focus on developing a high-quality risk management model for product quality?,6,Getting Started,What theories,tools and lessons learned in risk analysis can help address these questions?,Given the need for a significant shift in the approach to risk management,how do we begin the change process?,Are there off-the-shelf models and tools that might be used,i.e.,at a pilot-scale?,What kinds of RM processes can be used to foster changes needed both the regulatory and industrial spheres?,7,基本风险分析,8,Starting with the Some Basics,Risk,is intuitive and familiar to everyone,yet few among us define risk carefully and formally enough for complex risk analysis.,exposure,exposure,severity,probability,harm,hazard,chance,severity,value,probability,chance,9,风险,=“,暴露程度相对于,损失的机会,”,(,或者,风险,=“chance of losing something we value”),风险,=,危害,x,暴露程度,风险,后果,=,危害,x,暴露程度,10,同时期的风险分析,主要包括四大行动,:,危害识别,风险评估,风险管理,风险交流,11,风险管评估先于风险管理,Risk assessment is not a single process,but “a systematic approach to organizing and analysing scientific knowledge and information”to support a risk decision.,NRC(1994),Various paradigms exist for the,execution,of a risk assessment in public health;however,all paradigms have in common,fundamental scientific principles,.,12,风险评估需要问以下问题,:,什么会出错,?,出错的可能性是什么,?,后果是什么,?,13,风险管理需要问以下问题,:,可以做什么,?,那些方法是可用的,?,就风险、利益和成本而言什么是风险的交易物,?,目前的对将来的管理决定的影响是什么,?,14,Roles/Tasks(-short list),Pose the risk question.,Charge the Risk Assessors with the Risk Assessment Task.,Convene stake holders.,Analyze decision options.,Make/recommend the decision.,Identify data and gather information on the nature,extent,magnitude and uncertainty of the risk.,Write the Risk Assessment.,Recommends changes to RM questions.,Risk Managers,Risk Assessors,15,风险评估,Regulatory Policy,Risk Assessment,:(e.g.,Biotechnology RA to determine the need for risk management regulation.),Applied Risk Assessment,:To determine compliance with a regulation or policy.,Safety Assessments,:Highly defined risk calculations.Usually under a“bright line”safety policy.,16,Safety vs.Risk,Risk Limit,e.g.,Limit exceeded“10 times in 100”,Safety Limit,“Unsafe”,“Safe”,e.g.,Declared“unsafe”,Estimates of risk,17,民主的风险分析,风险评估为风险分析提供事实,.,风险,风险,风险,风险,风险,风险,风险,风险评估,风险,风险,风险,风险,风险,风险,风险,Worst,18,Risk Analysis in a Democracy,The risk,management,decisions about which risks to manage are value-laden decisions.,Risk Management,Risk,Risk,Risk,Risk,Risk,Risk,Risk,Risk,Risk,Risk,Risk,Risk,Risk,Risk,Values,Costs,Worst,Risk Management Rank,19,Translating Risk Analytic Paradigms,Risk Analysis,Risk Assessment,Release Assessment,Exposure Assessment,Consequence Assessment,Risk Estimation,Risk Management,Risk Communication,Hazard Identification,What can go wrong?,What are the consequences?,What is the likelihood that it would go wrong?,What can be done?,What are the trade-offs in terms of costs,benefits and risks?,What is the impact of decisions on future RM options?,Risk Assessment,PQ Failures,Exposure Assessment,Consequence Assessment,Risk Estimation,A simple change to apply a contemporary model.,20,Possible Stages of Risk Assessment for Work Planning,21,Hazard Identification,What can go wrong?,Identify hazards:,events,Identify hazardous,agents,(chemical,biological,physical),How severe are the potential consequences,?,Given the event occurs,is the consequence catastrophic?Mildly annoying?,How likely are the events to occur,?,Essentially a crude risk estimate for initial prioritization purposes.,22,Exposure Assessment,Release Assessment:,How“,much,”of the hazardous event occurs,?,Example:Does a“non-sterile”event involve 1 or 10,000 vials?,Pathway analysis:,If the hazardous event occurs,what pathways are there that expose humans to the hazard,?,Extent of exposure:,If a hazardous event occurs,how many people are potentially exposed,?,23,GMP Failure(Release)Assessment,How frequent are the identified PQ events(hazards)?,Boundary of release?Process line,plant,warehouse,distributor?,Release rates(“PQ Faults”)are obtained in fault tree assessments,empirically,historical data,e