企业质量风险管理中英文对照

1、Tabieof【最te新资料亠 WORD文档§目录可编辑修改亠I人【Xi1. INTRODUCTION-1引言J1'丿、2. SCOPE范围3. PRINCIPLES OF QUALITY RISK MANAGEMENT质量风险管理原理4. GENERAL QUALITY RISK MANAGEMENT PROCESS质量风险管理基本程序4.1 Resp on sibilities职责分配4.2 In itiat ing a Quality Risk Man ageme nt Process质量风险管理的启动4.3 Risk Assessme nt风险评估4.4 Risk C

2、on trol风险控制4.5 Risk Commu ni cati on风险交流4.6 Risk Review风险回顾5. RISK MANAGEMENT METHODOLOGY风险管理方法学6. INTEGRATION OF QUALITY RISK MANAGEMENT INTO INDUSTRY ANDREGULATORY OPERATIONS工业及监管与质量风险管理的整合7. DEFINITIONS定义8. REFERENCES参考资料Annex I: Risk Man ageme nt Methods and Tools附件I:风险管理方法及工具I.1 Basic Risk Mana

3、gement Facilitation MethodsI.1基本风险管理简易方法I.2 Failure Mode Effects An alysis (FMEA)I.2失误模式影响分析(FMEA)I.3 Failure Mode, Effects and Criticality An alysis (FMECA)I.3失误模式影响及危险程度分析(FMECA)I.4 Fault Tree An alysis (FTA)I.4故障树型分析(FTA)I.5 Hazard An alysis and Critical Con trol Points (HACCP)I.5危害分析及关键控制点(HACCP

4、)I.6 Hazard Operability An alysis (HAZOP)I.6危害可操作性分析(HAZOP)I.7 Preliminary Hazard Analysis (PHA)I.7初步危害分析(PHA)I.8 Risk Ranking and FilteringI.8风险排序及滤除I.9 Supporting Statistical ToolsI.9辅助统计工具Annex II: Potential Applications for Quality RiskMan ageme nt附件II:质量风险管理潜在应用前景.II.1 Quality Risk Man ageme nt

5、 as Part of I ntegratedII.1综合质量管理中的质量风险管理Quality Man ageme nt11.2 Quality Risk Management as Part of Regulatory Operati ons11.3 Quality Risk Man ageme nt as Part of developme nt11.4 Quality Risk Management for Facilities,Equipme nt and Utilities11.5 Quality Risk Management as Part of MaterialsMan ag

6、eme nt11.6 Quality Risk Management as Part of Production11.7 Quality Risk Management as Part of LaboratoryControl and Stability Studies11.8 Quality Risk Man ageme nt as Part of Packag ing and Labelli ng1. INTRODUCTIONRisk management principles are effectively utilized in many areas of bus in ess and

7、 gover nment in clud ing finan ce, in sura nee, occupati onal safety, public health, pharmacovigila nee, and by age ncies regulati ng these in dustries. Although there are some examples of the use of quality risk management in the pharmaceutical industry today, they are limited and do not represe nt

8、 the full contributions that risk management has to offer. In addition, the importanee of quality systems has been recognized in the pharmaceutical industry and it is I beco ming evide nt that quality risk man ageme nt is a valuable comp onent of an effective quality system.It is commonly understood

9、 that risk is defined as the comb in ati on of the probability of occurre nee ofharm andthe severity of that harm. However, achieving a shared understanding of the application of risk management among diverse stakeholders is difficult because each stakeholder might perceive differe nt pote ntial har

10、ms, place a different probability on each harm occurring andII.2操作优化中的应用II.3研发中的应用II.4对工具、设备和设施的质量风险管理II.5物料管理中的应用II.6生产中的应用II.7实验室控制及稳定性研究中的应用II.8标签及包装中的应用引言风险管理原理在商业和政府的许多领域都得到了有效 应用，如：金融、保险、职业安全、公共卫生、药物 监测及相应的监管部门。如今质量风险管理在药企中 虽有应用，但范围有限，并没有发挥岀它的全部效 用。药企已经意识到了质量体系的重要性，而质量风 险管理越来越明显地成为有效质量体系的重要组分。

11、根据常规理解，风险被定义为伤害发生的可能性及严 重程度。然而，要在不同利益集团之间寻求风险管理 应用方面的共同认识是相当困难的，因为他们认识到 的潜在危害、各危害发生的可能性及严重程度都不 同。药品相关的利益集团很多，如病人、医疗人员和 政府企业，但是质量风险管理的首要目的是保护病 人。attribute differe nt severities to each harm .In relati on topharmaceuticals, although there are a variety ofstakeholders, in clud ing patie nts and medical

12、 practiti on ersas well as gover nment and in dustry, the protecti on of thepatient by managing the risk to quality should becon sidered of prime importa nee.The man ufacturi ng and use of a drug (medic in al) product, including its components, necessarily entail some degree of risk. The risk to its

13、 quality is just one component of the药品生产、使用过程，包括药品的成分，都会不可避免地引入一定的风险。质量风险只是其中的一部分。|在产品整个生命周期中，确保产品的质量，使得药品_|overall risk. It is important to understand that product质量方面的重要性质与临床研究中的一致，做到这些quality should be maintained throughout the product是非常重要的。一个有效的质量风险管理方法能通过lifecycle such that the attributes tha

14、t are important to the|提供前摄措施，确疋控制研发和生产中潜在的质量冋|quality of the drug (medic in al) product rema in con siste nt|题，来进一步确保药品质量。当质量问题岀现时，应|with those used in the cli ni cal studies. An effective quality用质量风险管理还能改善决策过程。有效进行质量风risk management approach can further ensure the high险管理能促使产生更好更正式决策，增强监控者对公quali

15、ty of the drug (medic in al) product to the patie nt by司处理潜在风险能力的信心，积极影响直接监理的程providi ng a proactive means to ide ntify and con trol度和水平。potential quality issues during development andman ufacturi ng. Additi on ally, use of quality riskman ageme nt can improve the decisi on making if a quality's

16、 ability toproblem arises. Effective quality risk man ageme nt can facilitate better and more in formed decisi ons, can provide regulators with greater assura nee of a compa ny deal with potential risks and can beneficially affect the exte nt and level of direct regulatory oversight.The purpose of t

17、his docume nt is to offer a systematic此文件的目的是提供质量风险管理方面的系统方approach to quality risk management. It serves as a foun dati on or resource docume nt that is in depe ndent of,I法。作为一个基础性、资源性的文件，它独立于却又支持其它ICH质量文件，补充药企和监管机构内已有的yet supports, other ICH Quality docume nts and compleme nts existi ng quality pr

18、actices, requireme nts, sta ndards, and guideli nes with in the pharmaceutical in dustry and regulatory en vir onmen t. It specifically provides guida nee on the pri nciples and some of the tools of quality risk management that can enable more effective and con siste nt risk based decisi ons, both b

19、y regulators and in dustry, regard ing the quality of drug substa nces and drug (medic in al) products across the product lifecycle. It is not inten ded to create any new expectati ons bey ond the curre nt regulatory requireme nts.质量措施、要求、标准和指南。特别是它提供了一些 质量风险管理工具的原理指南，这些工具能促使监管 者和企业考虑整个产品周期中药用物质和药品的

20、质 量，做出更有效、更连续的基于风险的决策，并不想 在现有法规之外提岀新的期望。It is neither always appropriate nor always necessary to use a formal risk man ageme nt process (us ing recog ni zed tools and/ or internal procedures e.g., sta ndard operati ng procedures). The use of in formal risk man ageme nt processes (us ing empirical to

21、ols and/ or internal procedures) can also be con sidered acceptable.Appropriate use of quality risk management can facilitate but does not obviate in dustry' s obligati on to compregulatory requireme nts and does not replace appropriate commu ni cati ons betwee n in dustry and regulators.应用正式的风险

22、管理程序并非总是合适的或必要的（用已承认的工具或内部程序，如标准操作规程）。有时也允许使用非正式的风险管理程序（用经验工具或内部程序）。恰当运用风险管理能方便但不消除企业遵守法规 要求的责任，也不能取代企业和监管者之间必要的沟 通交流。y with2. SCOPE2.范围This guideli ne provides prin ciples and examples of tools for quality risk man ageme nt that can be applied to differe nt aspects of pharmaceutical quality. These

23、aspects本指南给岀了质量风险管理工具的原理和应用实例，这些工具可用于药品质量各方面，即药用物质、药品、生物和生物技术产品（包括药品中用到的原料、溶剂、赋形include development, manufacturing, distribution, and the剂、包装标签材料等） 生命周期中的研发、生产、销售、in specti on and submissi on/review processes throughout the检察、提交和复审各过程。lifecycle of drug substa nces, drug (medic in al) products,3.质量风险

24、管理原理biological and biotech no logical products (in cludi ng the use of raw materials, solve nts, excipie nts, packag ing and labeli ng materials in drug (medic in al) products, biological and biotech no logical products).3. PRINCIPLES OF QUALITY RISK质量风险管理的两条基本原理是：1. 评估质量风险应基于科学知识并最终同对病人的保 护联系起来。2.

25、投入的努力程度、管理的正式程度及文件管理水平 应与风险水平相适应。MANAGEMENTTwo primary principles of quality risk management are: ? The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patie nt; and4.质量风险管理基本过程? The level of effort, formality and documentation o

26、f the quality risk man ageme nt process should be comme nsurate with the level of risk.4. GENERAL QUALITY RISK MANAGEMENT质量风险管理是对药品质量风险进行评估，控制，交 流和审查的系统过程，这一过程贯穿药品整个生命周 期。图1给岀了这方面的一个模型，其他模型也有应 用。具体情况不同，框架中各组分受重视水平会各有 差别，可是一个有效的管理过程会将所有因素纳入考 虑，各因素受关注程度会因风险的特异而各有区别PROCESSQuality risk man ageme nt is a

27、 systematic process for the assessme nt, con trol, commu ni cati on and review of risks to the quality of the drug (medic in al) product across the product lifecycle. A model for quality risk management is outl ined in the diagram (Figure 1). Other models could be used. The emphasis on each comp one

28、nt of the framework might differ from case to case but a robust process will in corporate con siderati on of all the eleme nts at a level of detail that is comme nsurate with the specific risk.Figure 1:典型质量风险管理过程简介启动质量风险管理风险管理工具由于决策行为随时都可能发生，上图就没有显示决策 点。这些决策有可能被反馈到上一步以寻求更多信 息，这些信息可用于调整风险模型；也可能用于管理 过

29、程的终止。注解：图中的“不可接受”项不仅指违 背了法令法规要求，也表示风险管理过程需要重头再 来。Decisi on no des are not show n in the diagram above because decisions can occur at any point in the process. These decisi ons might be to retur n to the previous step and seek further information, to adjust the risk models or even to term in ate the

30、risk man ageme nt process based upon in formati onthat supports such a decisi on.Note:“ unacceptable in”he flowchart does not only refer to statutory, legislative or regulatory requirements, but also to the need to revisit the risk assessment process.4.1 Resp on sibilities4.1.职责分配Quality risk manage

31、ment activities are usually, but not质量风险管理经常是但也不总是由交叉学科团队执always, undertaken by interdisciplinaryteams. When行。除了要有风险管理方面的经验人士，团队还应包teams are formed, they should include experts from the括相关领域的专家（例如：质量小组、事业发展、工appropriate areas (e.g., quality un it, bus in ess developme nt.程、管理，生产、行销、法律、统计和临床方面等。engin

32、 eeri ng, regulatory affairs,producti on operati ons,决策者必须负责组织协调各部门之间的关系，保障团sales and marketing, legal, statistics and clinical)in队各项功能的有效发挥，确保整个管理过程得以合理addition to individuals who are knowledgeable about the展开、不断完善、反复审查，保障有足够的资源供团quality risk man ageme nt process.队使用。Decisi on makers should? take r

33、esp on sibilityfor coord in at ingquality riskmanagement across various functions and departments oftheir orga ni zati on; and? assure that a quality risk management process is defined,deployed and reviewed and that adequate resources areavailable.4.2 In itiat ing a Quality Risk Man ageme nt Process

34、4.2质量风险管理的启动Quality risk man ageme nt should in clude systematic质量风险管理应包括这样一些系统程序，这些设计好processes desig ned to coord in ate, facilitate and improve的程序用来协调，推动和改善那些风险方面基于科学science-based decision making with respect to risk.认识的决定。一项管理程序的发起和设计可能要经过Possible steps used to initiate and plan a quality risk如下

35、步骤：man ageme nt process might in clude the follow ing:?定义存在的难题和风险问题，包括识别潜在风险的相? Define the problem and/or risk question, including关假设；pertinent assumptions identifying the potential for risk;?收集风险评估相关的关于潜在危险、危害或人体健康? Assemble background information and/ or data on the影响的背景信息和数据；pote ntial hazard, ha

36、rm or huma n health impact releva nt to?确定领导人和重要资源；the risk assessme nt;?详细说明决策的时间表，可交付性和适当的标准。? Ide ntify a leader and n ecessary resources;? Specify a timeline, deliverables and appropriate level of decisi on making for the risk man ageme nt process.4.3 Risk Assessme ntRisk assessment consists of

37、the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards (as defined below). Quality risk assessme nts begi n with a well-defi ned problem descripti on or risk question. When the risk in question is well defined, an appropriate risk management

38、tool (see examples in secti on 5) and the types of in formati on n eeded to address the risk question will be more readily identifiable. As an aid to clearly defining the risk(s) for risk assessment purposes, three fun dame ntal questi ons are ofte n helpful:1. What might go wrong?2. What is the lik

39、elihood (probability) it will go wrong?3. What are the con seque nces (severity)?Risk identificationis a systematic use of information toidentify hazards referring to the risk question or problem description. Informationcan include historical data,theoretical an alysis, in formed opinions, and the c

40、on cer ns of stakeholders. Risk identification addresses the “ What might go wrong? ” question, including identifyingthepossible con seque nces. This provides the basis for further steps in the quality risk man ageme nt process.Risk analysis is the estimation of the risk associated with the identifi

41、ed hazards. It is the qualitative or quantitative process of linking the likelihood of occurrenee and4.3风险评估风险评估：此过程进行危险确认并对接触这些危险所 带来的风险进行分析评价。它以一个定义明确的难点 描叙或风险问题开始，当风险明确后，选择合适而有 针对性的管理工具和信息类型将会变得更容易。以下 三个基本问题将有助于给岀风险的清晰定义。1. 什么可能会出错？2. 岀错的可能性有多大？3. 岀错的后果和严重性有哪些？风险鉴定： 参照风险问题或难点描叙，系统利用已有 信息去鉴定危险。这些信

42、息包括历史数据、理论分 析、多方面观点和风险承担人的意见。风险鉴定时提 出“什么会出错”这一问题，同时还确定可能答案。 这一过程为后续步骤奠定了基础。风险分析： 估计与已确认危险相联系的风险，这是对危害发生的可能性和严重程度进行定性和定量分析的过程。风险评价中同样也应用到某些管理工具检测危severity of harms. In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk.害的能力（检测能力）。Risk eva

43、luation compares the identified and analyzed risk against given risk criteria. Risk evaluations consider the stre ngth of evide nee for all three of the fun dame ntal questi ons.In doing an effective risk assessme nt, the robust ness of the data set is important because it determines the quality of

44、the output. Reveali ng assumpti ons and reas on able sources of un certa inty will enhance con fide nee in this output and/or help identify its limitations. Uncertainty is due to comb in ati on of in complete kno wledge about a process and its expected or unexpected variability. Typical sources of u

45、n certa intyin cludegaps in kno wledge gaps inpharmaceutical scie nee and process un dersta nding, sources of harm (e.g., failure modes of a process, sources of variability), and probability of detecti on of problems.The output of a risk assessment is either a quantitative estimate of risk or a qual

46、itative description of a range of risk. When risk is expressed quantitatively, a numerical probability is used. Alter natively, risk can be expressed using qualitative descriptors, such as“ high ”"low "which should be defined in as much detail as possible. Sometimes a "risk score"

47、; is used to further defi ne descriptors in risk ranking. Inqua ntitativeriskassessments, a risk estimate provides the likelihood of a specific consequenee, given a set of risk-generating风险评估：将经过分析和鉴定的风险同给定标准作比 较，考虑三个基本问题的证据力。风险评估中，数据 的有效性决定了评估结果的质量。揭示、设想、分析 不确定性的来源将有助于增强对结果的信心、识别结 果的局限性。对过程了解不充分、过程

48、中可预见及不 可预见变动的发生，都将导致不确定性的发生。知识 结构的不完整，有限的药学发展水平、不充分的过程 理解、危险来源（不成功的过程模式、变动的来源）及 问题被发现的可能性都是不确定性的典型来源。评估结果可以是对风险的定量表示，也可以是对分险程度的定性描述。定量表示时可用数值表示可能性，用 高、中、低来给风险排序时，各个词的适用范围都 要详细规定，有时候还用到风险评分来进一步定义。 定量评估能对给定的风险衍生环境中特定结果发生的 可能性做岀判断。因此，定量评估一次只能评判一个 特定结果。于是一些管理工具用到相对衡量尺度，将 多重水平的严重性和可能性结合起来，以完成对相对 风险的整体评估。

49、评分过程的中间步骤有时也用到定 量风险估计方法。“I-刀,medium , orcircumstances. Thus, quantitative risk estimation is useful for one particular con seque nee at a time. Alter natively, some risk management tools use a relative risk measure to combine multiple levels of severity and probability into an overall estimate of re

50、lative risk. The in termediate steps within a scori ng process can sometimes employ quantitative risk estimation.4.4 Risk Con trolRisk control includes decision making to reduce and/or accept risks. The purpose of risk control is to reduce the risk to an acceptable level. The amount of effort used f

51、or risk control should be proportional to the significance of the risk. Decision makers might use different processes, includingbenefit-cost analysis, for understanding theoptimal level of risk con trol.Risk con trol might focus on the follow ing questi ons:? Is the risk above an acceptable level? W

52、hat can be done to reduce or elim in ate risks? What is the appropriate bala nce among ben efits, risks and resources? Are new risks introduced as a result of the identified risks being con trolled?Risk reduction focuses on processes for mitigation or avoidance of quality risk when it exceeds a spec

53、ified (acceptable) level (see Fig. 1). Risk reduction might include actions taken to mitigate the severity and probability of harm. Processes that improve the detectability of hazards and quality risks might also be4.4风险控制风险控制包括风险抑低和风险接受两方面的决策过程，进行控制的目的是将风险降低到可接受水平，投入努力量应与风险的严重程度相衬。决策者应用包括 效益-耗费比分析在

54、内的不同的程序去理解风险控制的 最佳水平。风险控制过程中以下问题会受到关注： 风险水平是否高于可接受水平之上？ 怎样做才能降低乃至消除风险？ 如何寻求效益、风险和资源之间的合适平衡？ 对已确定风险进行控制时是否会引入新的风险？风险抑低：此过程着力于减轻或避免超过一定水平（可接受水平）的质量风险，包括为减轻危害严重性和发生 可能性而采取的一系列措施，还包括一些致力于改善 危险及质量风险可检测性的程序。风险抑低过程可能 会给系统带入新的风险，其他业已存在的风险的严重 程度也可能增加。因此，完成风险抑低程序后，有必used as part of a risk control strategy. Th

55、e implementation of risk reduction measures can introduce new risks into the system or in crease the sig nifica nee of other exist ing risks. Hence, it might be appropriate to revisit the risk assessme nt to ide ntify and evaluate any possible cha nge in risk after implementing a risk reduction proc

56、ess.要再重复一下质量评估过程，来识别和评价风险系统 的可能变化。Risk acceptanee is a decision to accept risk. Risk风险接受：就是接受风险的决定。它可能为接受残留accepta nee can be a formal decisi on to accept the residual风险的正式决定，也可以是忽略剩余风险的消极决risk or it can be a passive decision in which residual risks定。有些类型的风险，即使用最好的质量风险管理手are not specified. For some types of harms, eve n the best段，也不能完全清除。在这种情形下，应确认使用了quality risk management practices might not entirely合适的风险管理策略，且风险已被降至特定水平（可接elim in ate risk. In these circumsta nces, it might be agreed受水平）。这个可接受水平由很多参数和各例具体情况that an appropriate quality risk management strategy has来确定。been applied and that qu