Q9质量风险管理中英文对照.doc

【精品文档】如有侵权，请联系网站删除，仅供学习与交流Q9质量风险管理中英文对照.精品文档.QUALITY RISK MANAGEMENTQ9工业指南Q9质量风险管理美国健康与公众服务部食品药品监督管理局（FDA）药品评价与研究中心（CDER）生物评价与研究中心(CBER)2006年6月人用药物注册技术要求国际协调会议（ICH）Table of Contents目录1. INTRODUCTION 引言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 Responsibilities 职责分配4.2 Initiating a Quality Risk Management Process 质量风险管理的启动4.3 Risk Assessment 风险评估4.4 Risk Control 风险控制4.5 Risk Communication 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 AND REGULATORY 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 Management Methods and Tools 附件 I:风险管理方法及工具I.1 Basic Risk Management Facilitation Methods I.1 基本风险管理简易方法I.2 Failure Mode Effects Analysis (FMEA) I.2 失误模式影响分析(FMEA)I.3 Failure Mode, Effects and Criticality Analysis (FMECA) I.3 失误模式影响及危险程度分析 (FMECA)I.4 Fault Tree Analysis (FTA) I.4 故障树型分析(FTA)I.5 Hazard Analysis and Critical Control Points (HACCP) I.5 危害分析及关键控制点(HACCP)I.6 Hazard Operability Analysis (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 Filtering I.8 风险排序及滤除I.9 Supporting Statistical Tools I.9 辅助统计工具Annex II: Potential Applications for Quality Risk Management 附件 II: 质量风险管理潜在应用前景.II.1 Quality Risk Management as Part of Integrated Quality Management II.1 综合质量管理中的质量风险管理II.2 Quality Risk Management as Part of Regulatory Operations II.2 操作优化中的应用II.3 Quality Risk Management as Part of development II.3 研发中的应用II.4 Quality Risk Management for Facilities, Equipment and Utilities II.4 对工具、设备和设施的质量风险管理II.5 Quality Risk Management as Part of Materials Management II.5 物料管理中的应用II.6 Quality Risk Management as Part of Production II.6 生产中的应用II.7 Quality Risk Management as Part of Laboratory Control and Stability Studies II.7 实验室控制及稳定性研究中的应用II.8 Quality Risk Management as Part of Packaging and Labelling II.8 标签及包装中的应用1. INTRODUCTION引言Risk management principles are effectively utilized in many areas of business and government including finance, insurance, occupational safety, public health, pharmacovigilance, and by agencies regulating these industries. Although there are some examples of the use of quality risk management in the pharmaceutical industry today, they are limited and do not represent the full contributions that risk management has to offer. In addition, the importance of quality systems has been recognized in the pharmaceutical industry and it is becoming evident that quality risk management is a valuable component of an effective quality system. 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，并没有发挥出它的全部效用。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。It is commonly understood that risk is defined as the combination of the probability of occurrence of harm and the 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 different potential harms, place a different probability on each harm occurring and attribute different severities to each harm. In relation to pharmaceuticals, although there are a variety of stakeholders, including patients and medical practitioners as well as government and industry, the protection of the patient by managing the risk to quality should be considered of prime importance. 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。The manufacturing and use of a drug (medicinal) product, including its components, necessarily entail some degree of risk. The risk to its quality is just one component of the overall risk. It is important to understand that product quality should be maintained throughout the product lifecycle such that the attributes that are important to the quality of the drug (medicinal) product remain consistent with those used in the clinical studies. An effective quality risk management approach can further ensure the high quality of the drug (medicinal) product to the patient by providing a proactive means to identify and control potential quality issues during development and manufacturing. Additionally, use of quality risk management can improve the decision making if a quality problem arises. Effective quality risk management can facilitate better and more informed decisions, can provide regulators with greater assurance of a companys ability to deal with potential risks and can beneficially affect the extent and level of direct regulatory oversight. 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，使得药品质量方面的重要性质与临床研究中的一致，做到这些是非常重要的。一个有效的质量风险管理方法能通过提供前摄措施，确定控制研发和生产中潜在的质量问题，来进一步确保药品质量。当质量问题出现时，应用质量风险管理还能改善决策过程。有效进行质量风险管理能促使产生更好更正式决策，增强监控者对公司处理潜在风险能力的信心，积极影响直接监理的程度和水平。The purpose of this document is to offer a systematic approach to quality risk management. It serves as a foundation or resource document that is independent of, yet supports, other ICH Quality documents and complements existing quality practices, requirements, standards, and guidelines within the pharmaceutical industry and regulatory environment. It specifically provides guidance on the principles and some of the tools of quality risk management that can enable more effective and consistent risk based decisions, both by regulators and industry, regarding the quality of drug substances and drug (medicinal) products across the product lifecycle. It is not intended to create any new expectations beyond the current regulatory requirements. 此文件的目的是提供质量风险管理方面的系统方法。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出新的期望。It is neither always appropriate nor always necessary to use a formal risk management process (using recognized tools and/ or internal procedures e.g., standard operating procedures). The use of informal risk management processes (using empirical tools and/ or internal procedures) can also be considered acceptable. Appropriate use of quality risk management can facilitate but does not obviate industrys obligation to comply with regulatory requirements and does not replace appropriate communications between industry and regulators. 应用正式的风险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。2. SCOPE 2. 范围This guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality. These aspects include development, manufacturing, distribution, and the inspection and submission/review processes throughout the lifecycle of drug substances, drug (medicinal) products, biological and biotechnological products (including the use of raw materials, solvents, excipients, packaging and labeling materials in drug (medicinal) products, biological and biotechnological products). 本指南给出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、赋形剂、包装标签材料等）生命周期中的研发、生产、销售、检察、提交和复审各过程。3. PRINCIPLES OF QUALITY RISK MANAGEMENT 3.质量风险管理原理Two 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 patient; and The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of 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. 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。4. GENERAL QUALITY RISK MANAGEMENT PROCESS 4. 质量风险管理基本过程Quality risk management is a systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle. A model for quality risk management is outlined in the diagram (Figure 1). Other models could be used. The emphasis on each component of the framework might differ from case to case but a robust process will incorporate consideration of all the elements at a level of detail that is commensurate with the specific risk. 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给出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。Figure 1:典型质量风险管理过程简介启动质量风险管理风险鉴定风险分析风险评估风险评估风险质量管理的效果/结果风险降低风险接受风险控制事件审核风险交流风险管理工具不合格Decision nodes are not shown in the diagram above because decisions can occur at any point in the process. These decisions might be to return to the previous step and seek further information, to adjust the risk models or even to terminate the risk management process based upon information that supports such a decision. Note: “unacceptable” in the flowchart does not only refer to statutory, legislative or regulatory requirements, but also to the need to revisit the risk assessment process. 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。4.1 Responsibilities 4.1. 职责分配 Quality risk management activities are usually, but not always, undertaken by interdisciplinary teams. When teams are formed, they should include experts from the appropriate areas (e.g., quality unit, business development, engineering, regulatory affairs, production operations, sales and marketing, legal, statistics and clinical) in addition to individuals who are knowledgeable about the quality risk management process. Decision makers should take responsibility for coordinating quality risk management across various functions and departments of their organization; and assure that a quality risk management process is defined, deployed and reviewed and that adequate resources are available. 质量风险管理经常是但也不总是由交叉学科团队执行。除了要有风险管理方面的经验人士，团队还应包括相关领域的专家（ 例如：质量小组、事业发展、工程、管理，生产、行销、法律、统计和临床方面等。决策者必须负责组织协调各部门之间的关系，保障团队各项功能的有效发挥，确保整个管理过程得以合理展开、不断完善、反复审查，保障有足够的资源供团队使用。4.2 Initiating a Quality Risk Management Process 4.2 质量风险管理的启动Quality risk management should include systematic processes designed to coordinate, facilitate and improve science-based decision making with respect to risk. Possible steps used to initiate and plan a quality risk management process might include the following: Define the problem and/or risk question, including pertinent assumptions identifying the potential for risk; Assemble background information and/ or data on the potential hazard, harm or human health impact relevant to the risk assessment; Identify a leader and necessary resources; Specify a timeline, deliverables and appropriate level of decision making for the risk management process. 质量风险管理应包括这样一些系统程序，这些设计好的程序用来协调，推动和改善那些风险方面基于科学认识的决定。一项管理程序的发起和设计可能要经过如下步骤：定义存在的难题和风险问题，包括识别潜在风险的相关假设；收集风险评估相关的关于潜在危险、危害或人体健康影响的背景信息和数据；确定领导人和重要资源；详细说明决策的时间表，可交付性和适当的标准。4.3 Risk Assessment 4.3 风险评估Risk assessment consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards (as defined below). Quality risk assessments begin with a well-defined problem description or risk question. When the risk in question is well defined, an appropriate risk management tool (see examples in section 5) and the types of information needed to address the risk question will be more readily identifiable. As an aid to clearly defining the risk(s) for risk assessment purposes, three fundamental questions are often helpful: 1. What might go wrong? 2. What is the likelihood (probability) it will go wrong? 3. What are the consequences (severity)? 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出风险的清晰定义。1. 什么可能会出错？2. 出错的可能性有多大？3. 出错的后果和严重性有哪些？Risk identification is a systematic use of information to identify hazards referring to the risk question or problem description. Information can include historical data, theoretical analysis, informed opinions, and the concerns of stakeholders. Risk identification addresses the “What might go wrong?” question, including identifying the possible consequences. This provides the basis for further steps in the quality risk management process. 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。Risk analysis is the estimation of the risk associated with the identified hazards. It is the qualitative or quantitative process of linking the likelihood of occurrence and severity of harms. In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk. 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害的能力（检测能力）。Risk evaluation compares the identified and analyzed risk against given risk criteria. Risk evaluations consider the strength of evidence for all three of the fundamental questions. In doing an effective risk assessment, the robustness of the data set is important because it determines the quality of the output. Revealing assumptions and reasonable sources of uncertainty will enhance confidence in this output and/or help identify its limitations. Uncertainty is due to combination of incomplete knowledge about a process and its expected or unexpected variability. Typical sources of uncertainty include gaps in knowledge gaps in pharmaceutical science and process understanding, sources of harm (e.g., failure modes of a process, sources of variability), and probability of detection of problems. The output of a risk assessment is either a quantitative estimate of risk or a qualitative description of a range of risk. When risk is expressed quantitatively, a numerical probability is used. Alternatively, risk can be expressed using qualitative descriptors, such as “high”, “medium”, or “low”, which should be defined in as much detail as possible. Sometimes a "risk score" is used to further define descriptors in risk ranking. In quantitative risk assessments, a risk estimate provides the likelihood of a specific consequence, given a set of risk-generating circumstances. Thus, quantitative risk estimation is useful for one particular consequence at a time. Alternatively, some risk management tools use a relative risk measure to combine multiple levels of severity and probability into an overall estimate of relative risk. The intermediate steps within a scoring process can sometimes employ quantitative risk estimation. 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