发布时间 : 星期日 文章ICH-Q9质量风险管理更新完毕开始阅读7a1f14d511a6f524ccbff121dd36a32d7275c793
质量风险管理方法能进一步给患者提供高质量药物(医疗)产品质量的保证。另外，如果出现质量问题，则采用质量风险管理可以改善决策。有效的质量风险管理可以促使做出更好，更基于可靠信息的决策，可以为业界药政部门提供更强大应对潜在风险的能力的保证，并且会对药政监督的水平和范围直接产生有利影响。
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. 本文件的目的是提供一个质量风险管理的综合方法。其作为一个基础的或资源性的文件，其独立并支撑其它的ICH 质量文件，并对现有的质量实践、要求、标准以及制药行业指南与药政环境进行补充。其将明确提供质量风险管理的原理，以及一些工具，其可以确保在药政部门和业界在考虑到贯穿在整个产品生命周期的原料药和药物(医疗)产品质量时，做出更有效与更一致的基于风险的决策。其并未试图建立任何超越当前管理要求的新的要求。
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 industry’s obligation to comply with regulatory requirements and does not replace appropriate communications between industry and regulators.
使用一个正式的风险管理过程(使用公认的工具，和/或内部程序，例如标准操作程序)既不总是恰当的，也不总是必须的。采用非正式的风险管理过程(使用经验的工具，和/或内部程序)也是可以考虑接受。恰当运用质量风险管理可以促进，但并不能免除业界遵守药政要求的责任，也不能取代业界和药政部门之间适当的沟通。 2. SCOPE 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的原理以及一些工具的例子，其可以应用于药品质量的不同方面。这些方面包括开发、制造、分销以及原料药、药物(医疗)产品、生物和生物技术产品(包括在药物(医疗)产品、生物和生物技术产品中使用到的原料、溶剂、赋形剂、包装和标签材料) 整个生命周期的检查和注册/评审过程。
3. PRINCIPLES OF QUALITY RISK MANAGEMENT 质量风险管理的原则 Two primary principles of quality risk management are: 质量风险管理的两个基本原则为：
? The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient; and 应该基于科学知识和最终与对患者的保护相关联对质量风险进行评价；以及 ? The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk. 质量风险管理过程的力度、正式程度和文件化程度都应该与风险水平相适应。 4. GENERAL QUALITY RISK MANAGEMENT PROCESS 常规质量风险管理程序
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.
质量风险管理指的是对贯穿于药物(医疗)产品生产周期中的风险进行评估、控制、沟通及评审的系统过程。图中概括了质量风险管理模式(图 1)。也可以使用其他模式。所强调的构架中每个组成，可依不同情况而有所不同的，但一个完善的过程会更加详细地整合考虑到所有因素，其与具体的风险有相同的水平。 Figure 1: Overview of a typical quality risk management process 图 1：典型的质量风险管理过程概述
Initiate Quality Risk Management Process
启动风险管理过程 风险控制 Risk Assessment 风险评估 Risk Identification 风险辩识
Analysis Risk 风险分析
Risk Evaluationun 风险评价
不 接受
Risk Control 风险控制
Risk Reduction 风险降低
风Decision nodes are not shown in the diagram above because decisions can occur at 风Risk Acceptance 接受风险 险险any point in the process. These decisions might be to return to the previous step and 管沟理seek further information, to adjust the risk models or even to terminate the risk 通management process based upon information that supports such a decision. Note: 工具“unacceptable” in the flowchart does not only refer to statutory, legislative or Output / Result of the Quality Risk Management Process regulatory requirements, but also to the need to revisit the risk assessment process. 质量风险管理程序的输出/结果 unacceptable Risk Management tools Risk Communication Risk Review 风险评审 在上图中并未标明判断结点，因为判断可出现在这个过程中的任何一个点。这些判断将会退回到前一步，并寻求进一步的信息以调整风险模型，甚至根据支持这个判断的信息来终止风险管理过程。（注：在流程图中的“不接受”不仅仅是依据法定、立法或药政要求，同样也需要返回风险评估过程。） 4.1 Responsibilities职责
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.
风险管理活动通常，但并不总是，需要多学科的团队参与。当形成一个团队时，应当要包括适当领域的专家(例如，质量部门、商业开发、工程、药政、生产运行、销售和市场、法律和临床)，及精通质量风险管理过程的个人。 Decision makers should 决策者应当：
? take responsibility for coordinating quality risk management across various functions and departments of their organization; and
负责在其组织内各职能部门间协调质量风险管理；以及，
? assure that a quality risk management process is defined, deployed and reviewed and that adequate resources are available.
确保明确，开展与评审了质量风险管理过程，并有适当的资源。
4.2 Initiating a Quality Risk Management Process 启动质量风险管理过程
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:
质量风险管理包括那些用于协调、促进和改善做出与风险相关的基于科学的决策系统过程。可能用于启动和策划一个质量风险管理过程的步骤可能包括以下几点：
? Define the problem and/or risk question, including pertinent assumptions identifying the potential for risk;
明确问题和/或风险问题，包括辨识潜在风险相关假设；
? Assemble background information and/ or data on the potential hazard, harm or human health impact relevant to the risk assessment;
收集与风险评估相关的潜在危险、伤害或影响人体健康的背景信息和资料和/或数据；
? Identify a leader and necessary resources; 辩识领导与必要的资源；
? Specify a timeline, deliverables and appropriate level of decision making for the risk management process.
指定风险管理程序的时限、交付日期与决策水平。 4.3 Risk Assessment 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:
风险评估：其包括辨识危险因素与暴露在这些危险因素(定义于后)相关风险的分析和评估。质量风险评估开始于一个明确的问题或风险问题。当被讨论的风险被明确定义后，则将会很容易确定适当的风险管理工具(见第 5 节中的例子)和需要用于风险问题说明的资料类型。在风险评估时，作为明确定义风险的辅助工具，通常如下这三个基本问题是非常有用的： 1. What might go wrong? 什么可能出错?
2. What is the likelihood (probability) it will go wrong? 会出错的可能性(概率)是什么?
3. What are the consequences (severity)? 结果(严重性)是什么?
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.
风险辨识：其是指参照风险问题或问题描述，系统地运用信息来辨识危险因素。这些信息可能包括历史数据、理论分析、意见以及风险涉众的考虑。风险辨识关注“什么可能出错?”这个问题，包括辨识可能的结果。这为进一步的质量风险管理过程奠定了基础。
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：其是对风险所关联已经辨识了的危险因素进行估计。它是对发生事件可能性与及灾害严重性进行定量或定性过程。在一些风险管理工具中，探测伤害的能力(可检测性)同样是在估计风险中的因素。
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.
风险评价：其是比较已经辨识和分析的风险与给定的风险标准进行比较。风险评价考虑到了所有这三个基本问题的证据强度。
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.
在进行一个有效的风险评估时，数据集的完美性很重要，因为它决定了输出的质量。显示假设及合理资源不确定性将会加强输出的可靠性，并且/或有助于辨识其限度。不确定性是由于关于过程不完整的知识以及其期望的或非期望的变异性综合造成。典型的不确定来源包括制药科学知识差距、对过程理解差距、伤害来源(如一个过程的失效模式，变异行来源)以及发现问题概率。
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