ICH-Q9质量风险管理

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR
HUMAN USE
人用药注册技术要求国际协调会议
ICH Harmonised Tripartite Guideline
人用药注册技术要求国际协调会议三方协调后的指南
Quality Risk Management
质量风险管理
Current Step 4 version
现行第四步版本
dated 9 November 2005
2005 年十一月 9日
This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the
European Union, Japan and USA.
本指南由人用药注册技术要求国际协调会议专家工作组根据人用药注册技术要求国际协调会议程序开发并提交各方的药政部门咨询。

根据人用药注册技术要求国际协调会议程序第四步，推荐给欧盟、日本和美国药的政部门采用的最终
文本。

Document History
文件历史
Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 9 November 2005, this guideline is recommended for adoption to the three regulatory parties to ICH
在 2005 年 11 月 9 日的人用药注册技术要求国际协调会议上，本指南已经通过人用药注册技术要求国际协调会议第四步程序，本指南已经推荐给人用药注册技术要求国际协调会议三方的药政部门采用。

TABLE OF CONTENTS
目录
1. INTRODUCTION 简介 (1)
2. SCOPE 范围 (2)
3. PRINCIPLES OF QUALITY RISK MANAGEMENT 质量风险管理的原则 (2)
4. GENERAL QUALITY RISK MANAGEMENT PROCESS 常规质量风险管理程序 (2)
4.1 Responsibilities 职责 (4)
4.2 Initiating a Quality Risk Management Process 启动质量风险管理过程 (4)
4.3 Risk Assessment 风险评估 (4)
4.4 Risk Control风险控制 (5)
4.5 Risk Communication风险沟通 (6)
4.6 Risk Review 风险评审 (6)
5. RISK MANAGEMENT METHODOLOGY 风险管理方法
学 (7)
6. INTEGRATION OF QUALITY RISK MANAGEMENT INTO INDUSTRY AND REGULATORY OPERATIONS质量风险管理与业界及药政运行整合 (8)
7. DEFINITIONS 定义 (9)
8. REFERENCES 参考文献 (11)
Annex 附录 I: Risk Management Methods and Tools风险管理方法与工具...
12
I.1 Basic Risk Management Facilitation Methods基本风险管理简易方
法 (12)
I.2 Failure Mode Effects Analysis故障模式效应分析(FMEA) (12)
I.3 Failure Mode, Effects and Criticality Analysis 故障模式影响与严重性分析(FMECA) (13)
I.4 Fault Tree Analysis 故障树分析(FTA) (13)
I.5 Hazard Analysis and Critical Control Points危害分析关键控制点(HACCP) (14)
I.6 Hazard Operability Analysis 危害及可操作性分析(HAZOP) (14)
I.7 Preliminary Hazard Analysis 预先危险分析(PHA) (15)
I.8 Risk Ranking and Filtering风险排序及过滤 (15)
I.9 Supporting Statistical Tools辅助性统计工具 (16)
Annex 附录 II: Potential Applications for Quality Risk Management 实施质量风险管理的潜在机会 (16)
II.1 Quality Risk Management as Part of Integrated Quality Management 整合质量管理部分的质量风险管理 (16)
II.2 Quality Risk Management as Part of Regulatory Operations 药政操作部分的质量风险管理 (18)
II.3 Quality Risk Management as Part of development 开发部分的质量风险管理 (19)
II.4 Quality Risk Management for Facilities, Equipment and Utilities 厂房，设备和公用设施的质量风险管理 (19)
II.5 Quality Risk Management as Part of Materials Management 物料管理部分的质量风险管理 (21)
II.6 Quality Risk Management as Part of Production 生产部分的质量风险管理 (21)
II.7 Quality Risk Management as Part of Laboratory Control and Stability Studies 实验室控制和稳定性研究部分的质量
Quality Risk Management质量风险管理风险管理 (22)
II.8 Quality Risk Management as Part of Packaging and Labelling 包装和标签部分的质量风险管理 (22)
1. INTRODUCTION 导言
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.
风险管理原则被有效地应用于许多商业和政府的领域，包括金融、保险、职业安全、公共健康、药物预警，以及这些行业的主管部门。

如今，尽管在制药行业也有一些运用质量风险管理的例子，但其非常有限，且没有体现出风险管理能提供的全部贡献。

另外，制药行业已经认识到质量体系的重要性，而且，质量风险管理对一个有效的质量体系来说，是一个有价值的组成部分这一点越来越明显。

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.
通常将风险理解为，风险是由伤害发生的概率及伤害严重性结合而成。

然而，在不同的风险涉众中达成对风险管理应用共识仍是困难的，因为每个风险涉众可能感觉到不同的潜在伤害，对每个所发生的伤害设置不同的概率以及伤害不
同的严重性属性。

对于药品来说，尽管有多种的风险涉众，包括患者、医疗从业人员，以及政府和业界，运用质量风险管理都应该以保护病人为基本出发点。

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 co mpany’s ability to deal with potential risks and can beneficially affect the extent and level of direct regulatory oversight.
药物(医疗)产品制造和使用，包括它的组份，必然要承担一定程度的风险。

其质量风险仅是全部风险中的一个。

重要的是要了解到，产品质量应当贯穿产品的生命周期，这个属性对于药物(医疗)产品保持与临床研究时一致是非常重要的。

通过前瞻意义上辨识与控制在研发与制造中的潜在质量问题，一个有效的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 a nd/ 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 betwe en 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：
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
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.
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 identif y 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, includin g 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 qualitat ive description of a range of risk. When risk is expressed quantitatively, a numerical probability is used. Alternatively, risk can be expressed using quali tative 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.
风险评估的输出既是一个对风险定量估计也是一个对风险范围的定性描述。

当风险被定量地表达，则运用数值表达它的概率。

另外，风险还可以运用如“高”、“中”或“低”等定性描述词来表达，对其应该尽可能详细地确定。

一些时候，使用“风险记分”来进一步确定描述风险的排列。

在定量风险评估中，对一个风险估计能提供一个特定结果的可能性，给出一系列产生风险状况。

因此，定量风险评估对于在某个时间的特定后果非常有用。

另外，一些风险管理工具采用了相对的风险度量将多种级别的严重性和概率合并到一个完整的相对风险估计中。

在一个记分过程的中间步骤有时候可以使用定量风险评估。

4.4 Risk Control风险控制
Risk 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 for risk control should be proportional to the significance of the risk. Decision makers might use different processes, including benefit-cost analysis, for understanding the optimal level of risk control.
风险控制：其包括做出的降低和/或接受风险的决定。

风险控制的目的是降低风险到一个可接受的水平。

用于风险控制所作工作量应该与风险的显著性相称。

决策者可能会采用不同的过程，包括收益成本分析，来了解最佳的风险控制水平。

Risk control might focus on the following questions:
风险控制可能会集中在下列问题：
• Is the risk above an acceptable level?
是否风险超过了一个可接受的水平?
• What can be done to reduce or eliminate risks?
什么方法可以用来降低或消除风险?
• What is the appropriate balance among benefits, risks and resources?
效益、风险和资源之间的恰当的平衡点是什么?
• Are new risks introduced as a result of the identified risks being controlled?
控制已经所辨识的风险是否引入新的风险?
Risk reduction: focuses on processes for mitigation or avoidance of quality risk when it exceeds a specified (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 be used as part of a risk control strategy. The implementation of risk reduction measures can introduce new risks into the system or increase the significance of other existing risks. Hence, it might be appropriate to revisit the risk assessment to identify and evaluate any possible change in risk after implementing a risk reduction process.
风险降低：其是着眼于当风险超过了某个特定(可接受)水平(见图 1)后缓和或避免质量风险的过程。

风险降低可能包括用于减缓伤害的严重性和概率所采取的行动。

改善危险因素和质量风险可检测性的过程也可能作为一个风险控制策略中的一个部分。

通过实施风险降低措施，新的风险可能被引入到系统中或者显著增加其它已经存在的风险。

因此，在实施风险降低过程后，可能会适当地返回到风险评估中对风险中任何可能的改变进行辩识和评价。

Risk acceptance: is a decision to accept risk. Risk acceptance can be a formal decision to accept the residual risk or it can be a passive decision in which residual risks are not specified. For some types of harms, even the best quality risk management practices might not entirely eliminate risk. In these circumstances, it might be agreed that an appropriate quality risk management strategy has been applied and that quality risk is reduced to a specified (acceptable) level. This (specified) acceptable level will depend on many parameters and should be decided on a case-by-case basis.
接受风险：其是一个接受风险的决定。

风险接受可以是一个接受剩余风险的正式决定或者是当剩余风险不具体时的被动接受。

对于一些类型的伤害，甚至最好的质量风险实践也未必能全部消除风险。

这些情况下，可以认为已应用了恰当的质量风险管理策略，并且质量风险已降低到一个特定(可接受)的水平。

这个(特定)可接受的水平将会取决于许多参数，并且具体情况具体判断定。

4.5 Risk Communication风险沟通
Risk communication: is the sharing of information about risk and risk management between the decision makers and others. Parties can communicate at any stage of the risk management process (see Fig. 1: dashed arrows). The output/result of the quality risk management process should be appropriately communicated and documented (see Fig. 1: solid arrows). Communications might include those among interested parties; e.g., regulators and industry, industry and the patient, within a company, industry or regulatory authority, etc. The included information might relate to the existence, nature, form, probability, severity, acceptability, control, treatment, detectability or other aspects of risks to quality. Communication need not be carried out for each and every risk acceptance. Between the industry and regulatory authorities, communication concerning quality risk management decisions might be effected through existing channels as specified in regulations and guidances.
风险沟通：是在决策者和其它人员之间分享有关风险和风险管理的信息。

各方之间可以在任何风险管理过程阶段进行沟通(见图 1 的点划线箭头)。

质量风险管理过程的输出/结果应当进行适当的沟通和存档(见图 1 的实线箭头)。

沟通有可能包括这些相关方，例如，药政与业界、业界与患者、在一个公司、业界或药政当局内部等。

所包括的信息应该与质量风险的存在性、性质、形式、概率、严重性、可接受性、控制、处理、可检测性或其它有关方面。

沟通不需要对每个风险接受都进行。

如果在业界和药政当局之间，就可能受影响进行质量风险管理决策沟通，则这些沟通可能通过现有的规章或指南中所说明的渠道来进行。

4.6 Risk Review 风险评审
Risk management should be an ongoing part of the quality management process. A mechanism to review or monitor events should be implemented.
质量风险管理应当是质量管理过程中的一个进行部分。

应当实施一个评审或对事件进行监控的机制。

The output/results of the risk management process should be reviewed to take into account new knowledge and experience. Once a quality risk management process has been initiated, that process should continue to be utilized for events that might impact the original quality risk management decision, whether these events are planned (e.g., results of product review, inspections, audits, change control) or unplanned (e.g., root cause from failure investigations, recall). The frequency of any review should be based upon the level of risk. Risk review might include reconsideration of risk acceptance decisions (section4.4).
对风险管理过程输出/结果进行评审应当考虑采用新的知识和经验。

一旦开始了某个质量风险管理过程，则该过程应该一直应用于可能影响初始质量风险管理决策的事件，而不管那些事件是已被计划的(如产品评审、检查、审计、变更控制结果)或未计划的(如从失败调查的根本原因、检查、召回)。

评审频率应该取决于风险水平。

风险评审可能包括对风险接受决策重新考虑(4.4 节)。

5. RISK MANAGEMENT METHODOLOGY 风险管理方法学
Quality risk management supports a scientific and practical approach to decision-making. It provides documented, transparent and reproducible methods to accomplish steps of the quality risk management process based on current knowledge about assessing the probability, severity and sometimes detectability of the risk.
质量风险管理支持科学和实际方法来进行决策。

在现有关于风险概率，严重性和一些事件的可检测性评估知识的基础上，其提供文件的，透明的和可重复的方法来实现质量风险管理程序的步骤。

Traditionally, risks to quality have been assessed and managed in a variety of informal ways (empirical and/ or internal procedures) based on, for example, compilation of observations, trends and other
information. Such approaches continue to provide useful information that might support topics such as handling of complaints, quality defects, deviations and allocation of resources.
传统上，对于质量的风险的评估和管理是基于多种非正式的方式(经验的，和/或，内部程序)，例如，现象汇总、趋势和其它资料。

此类方法继续提供有用的信息，这些信息可以支持诸如处理投诉、质量缺陷、偏差与资源分配。

Additionally, the pharmaceutical industry and regulators can assess and manage risk using recognized risk management tools and/ or internal procedures (e.g., standard operating procedures). Below is a non-exhaustive list of some of these tools (further details in Annex 1 and chapter 8):
此外，制药业界与药政可以使用公认的风险管理工具，和/或，内部程序(例如，标准操作程序)来评估和管理风险。

以下并非是这些工具的一个详尽的列表(详细在附件 1 和第 8 章)：
• Basic risk management facilitation methods (flowcharts, check sheets etc.);
基本风险管理简易方法(流程图，核对单等)；
• Failure Mode Effects Analysis (FMEA); 故障模式效应分析(FMEA)；
• Failure Mode, Effects and Criticality Analysis (FMECA); 故障模式影响与严重性分析(FMECA)；
• Fault Tree Analysis (FTA); 故障树分析(FTA)；
• Hazard Analysis and Critical Control Points (HACCP); 危害分析关键控制点(HACCP)；
• Hazard Operability Analysis (HAZOP); 危害及可操作性分析(HAZOP)；• Preliminary Hazard Analysis (PHA); 预先危险分析(PHA)；
• Risk ranking and filtering; 风险排行与过滤；
• Supporting statistical tools. 辅助性统计工具。

It might be appropriate to adapt these tools for use in specific areas pertaining to drug substance and drug (medicinal) product quality. Quality risk management methods and the supporting statistical tools can be used in combination (e.g., Probabilistic Risk Assessment). Combined use provides flexibility that can facilitate the application of quality risk management principles.
在原料药和药物(医疗)产品质量的特定领域运用这些工具可能是恰当的。

质量风险管理方法以及辅助统计工具可以联合使用(如，概率性风险评估)。

联合使用提供了灵活性，而这种灵活性可以促进质量风险管理原则的应用。

The degree of rigor and formality of quality risk management should reflect available knowledge and be commensurate with the complexity and/ or criticality of the issue to be addressed.
质量风险管理的严格程度与和形式应当反映可利用的知识和所关注问题的复杂性，和/或严重性相当。

6. INTEGRATION OF QUALITY RISK MANAGEMENT INTO INDUSTRY AND REGULATORY OPERATIONS 质量风险管理与业界及药政运行整合
Quality risk manage ment is a process that supports science-based and practical decisions when integrated into quality systems (see Annex II). As outlined in the introduction, appropriate use of quality risk management does not obviate industry’s obligation to comply with regulatory requirements. However, effective quality risk management can facilitate better and more informed decisions, can provide regulators with greater assurance of a company’s ability to deal with potential risks, and might affect the extent and level of direct regulatory oversight. In addition, quality risk management can facilitate better use of resources by all parties.
质量风险管理是一个过程，当将其整合到质量体系中时(见附录 II)可以支持基于科学和实践的决策。

正如在简介中所简述的，恰当地运用质量风险管理并不能免除业界遵守药政的要求。

然而，有效的质量风险管理可以促使做出更好和更有远见的决策，它可以为管理者提供业界更多的应对潜在风险能力的保证并且可能会影响直接监管的范围和水平。

另外，质量风险管理可以促使资源能被所有部门更好地运用。

Training of both industry and regulatory personnel in quality risk management processes provides for greater understanding of decision-。