11月18日，ICH发布了新版ICH Q9（R1）《质量风险管理》
现将中英文对照版分享给大家:
ICH HARMONISED GUIDELINE
QUALITY RISK MANAGEMENT
Q9(R1)
ICH Q9（R1）质量风险管理
ICH Consensus Guideline
TABLE OFCONTENTS
目录
INTRODUCTION
介绍
SCOPE
范围
PRINCIPLES OFQUALITY RISK MANAGEMENT
质量风险管理的原则
GENERAL QUALITYRISK MANAGEMENT PROCESS
质量风险管理一般流程
Responsibilities
责任
Initiating aQuality Risk Management Process
启动质量风险管理流程
Risk Assessment
风险评估
Risk Control
风险控制
Risk Communication
风险沟通
Risk Review .
风险审核
RISK MANAGEMENTMETHODOLODY
风险管理方法
Formality inQuality Risk Management
质量风险管理的正式性
Risk-basedDecision Making
基于风险的决策
INTEGRATION OFQUALITY RISK MANAGEMENTINTO INDUSTRY AND REGULATORY OPERATIONS
将质量风险管理整合到行业和监管运营中
DEFINITIONS
定义
REFERENCES
参考文献
ANNEX I: QUALITYRISK MANAGEMENT METHODS AND TOOLS
附录I：质量风险管理方法和工具
I.1 Basic Risk Management Facilitation Methods
基本风险管理简化方法
I.2 Failure Mode Effects Analysis (FMEA)
失效模式影响分析（FMEA）
I.3 Failure Mode, Effects and CriticalityAnalysis (FMECA)
失效模式，影响和关键性分析
I.4 Fault Tree Analysis (FTA)
故障树分析（FTA）
I.5 Hazard Analysis and Critical Control Points(HACCP)
危害分析和关键控制点（HACCP）
I.6 Hazard Operability Analysis (HAZOP)
危害与可操作性分析（HAZOP）
I.7 Preliminary Hazard Analysis (PHA)
初步危害分析（PHA）
I.8 Risk Ranking and Filtering
风险排序和过滤
I.9 Supporting Statistical Tools
支持性统计学工具
ANNEX II:QUALITY RISK MANAGEMENTAS PART OFINTEGRATED QUALITY MANAGEMENT
附录Ⅱ：质量风险管理在质量管理中的应用
II.1 Quality Risk Management as Part of IntegratedQuality Management
质量风险管理作为综合质量管理的一部分
II.2 Quality Risk Management as Part of RegulatoryOperations
监管活动中的质量风险管理
II.3 Quality Risk Management as Part ofdevelopment
药物开发中的质量风险管理
II.4 Quality Risk Management for Facilities,Equipment and Utilities
设施，设备和公用系统中的质量风险管理
II.5 Quality Risk Management as Part of MaterialsManagement
物料管理中的质量风险管理
II.6 Quality Risk Management as Part of Production
药物生产中的质量风险管理
II.7 Quality Risk Management as Part of LaboratoryControl and Stability Studies
实验室控制和稳定性研究中的质量风险管理
II.8 Quality Risk Management as Part of Packagingand Labelling
包装和标签中的质量风险管理
II.9 Quality Risk Management as Part of SupplyChain Control
供应链控制中的质量风险管理
1. INTRODUCTION
介绍
Risk managementprinciples are effectively utilized in many areas of business and governmentincluding finance, insurance, occupational safety, public health,pharmacovigilance, and by agencies regulating these industries. In thepharmaceutical sector, the principles and framework of ICH Q9, coupled with theofficial ICH training material that supports this guideline, are instrumentalin enhancing the application of effective quality risk management by industryand regulators. The importance of quality systems has been recognized in thepharmaceutical industry and it is evident that quality risk management is avaluable component of an effective quality system.
风险管理原则在商业和政府的许多领域得到有效利用，包括金融、保险、职业安全、公共卫生、药物警戒以及监管这些行业的机构。在制药行业，ICH Q9的原则和框架，加上支持该指南的官方ICH培训材料，有助于加强行业和监管机构对有效质量风险管理的应用。质量体系的重要性在制药行业已经得到认可，很明显，质量风险管理是有效质量体系的宝贵组成部分。
It is commonlyunderstood that risk is defined as the combination of the probability ofoccurrence of harm and the severity of that harm. However, achieving a sharedunderstanding of the application of risk management among diverse stakeholdersis difficult because each stakeholder might perceive different potential harms,place a different probability on each harm occurring and attribute differentseverities to each harm. In addition, subjectivity can directly impact theeffectiveness of risk management activities and the decisions made. In relationto pharmaceuticals, although there are a variety of stakeholders, includingpatients and medical practitioners as well as government and industry, theprotection of the patient by managing the risk to quality and availability,when availability risks arise from quality/manufacturing issues, should beconsidered of prime importance.
通常理解，风险被定义为伤害发生概率和伤害严重程度的组合。然而，不同利益相关方之间很难对风险管理的应用达成共识，因为每个利益相关方说理解的潜在危害可能不同，对每种危害的所发生的概率设定不同，对每种危害所赋予的严重程度也不同。此外，主观性可以直接影响风险管理活动的有效性和所做出的决策。就药品而言，尽管有各种各样的利益相关方，包括患者和医疗从业人员以及政府和企业，但当质量/制造问题产生可用性风险时，应将管理质量和可用性风险来保护患者视为首要任务。
The manufacturingand use of a drug (medicinal) product, including its components, necessarilyentail some degree of risk. The risk to its quality is just one component of theoverall risk. It is important to understand that product quality is assuredbased on appropriate risk-based decision-making throughout the productlifecycle, such that the attributes that are important to the quality of thedrug (medicinal) product are maintained and the product remains safe andeffective.
药物（医疗）产品，包括其成分，的制造和使用必然会带来一定程度的风险。其质量风险只是整体风险的一个组成部分。重要的是要了解，在整个产品生命周期中，产品质量是根据基于风险的适当决策来保证的，这样对药物（医疗）产品质量至关重要的属性才能得到保持，并且产品保持安全有效。
An effectivequality risk management approach can further ensure the high quality of thedrug (medicinal) product to the patient by providing a proactive means toidentify and control potential quality issues during development andmanufacturing. A proactive approach to quality risk management facilitatescontinual improvement and is of strategic importance in achieving an effectivepharmaceutical quality system. Additionally, use of quality risk management canimprove the decision making if a quality problem arises. In the developmentphase, quality risk management is part of building knowledge and understandingrisk scenarios, so that appropriate risk control can be decided upon duringtechnology transfer, for use during the commercial manufacturing phase. In thiscontext, knowledge is used to make informed risk-based decisions, triggerre-evaluations and stimulate continual improvements. Effective and proactivequality risk management can facilitate better, more informed and timelydecisions throughout the lifecycle. This can provide regulators with greaterassurance of a company’s ability to deal with potential risks and avertproblems, and can beneficially affect the extent and level of direct regulatoryoversight.
有效的质量风险管理方法可以通过提供一种主动手段来识别和控制开发和制造过程中的潜在质量问题，从而进一步确保向患者提供高质量的药物（药用）产品。积极主动的质量风险管理方法有助于持续改进，对于实现有效的药品质量体系具有战略重要性。此外，如果出现质量问题，使用质量风险管理可以改善决策。在开发阶段，质量风险管理是建立知识和理解风险情景的一部分，以便在技术转移期间决定适当的风险控制，以便在商业制造阶段使用。在这种情况下，知识被用来做出基于风险的明智决策，触发重新评估并刺激持续改进。有效和主动的质量风险管理可以促进在整个生命周期中做出更好、更明智和及时的决策。这可以为监管机构提供更大的保证，确保公司处理潜在风险和避免问题的能力，并且可以有利地影响直接监管监督的程度和水平。
The application ofdigitalization and emerging technologies in the manufacture and control ofmedicinal products can present certain challenges. The application of qualityrisk management to the design, validation and technology transfer of advancedproduction processes and analytical methods, advanced data analysis methods andcomputerized systems is important.
数字化和新兴技术在医药产品制造和控制中的应用可能会带来一定的挑战。将质量风险管理应用于先进生产工艺和分析方法、先进数据分析方法和计算机化系统的设计、验证和技术转移非常重要。
The purpose ofthis document is to offer a systematic approach to quality risk management forbetter, more informed, and timely decisions. It serves as a foundation orresource document that is independent of, yet supports, other ICH Qualitydocuments 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 ofquality risk management that can enable more effective and consistent riskbased decisions, both by regulators and industry, regarding the quality of drugsubstances and drug (medicinal) products across the product lifecycle. It isnot intended to create any new expectations beyond the current regulatoryrequirements.
本文件的目的是提供一种系统的质量风险管理方法，以便更好、更明智、更及时地做出决策。它作为独立于其他ICH质量文件但支持的基础或资源文档，并补充了制药行业和监管环境中现有的质量实践、要求、标准和指南。它专门为质量风险管理的原则和一些工具提供指导，这些工具可以使监管机构和行业能够在整个产品生命周期中就活性成分和药物（药用）产品的质量做出更有效和一致的基于风险的决策。它无意在当前监管要求之外创造任何新的期望。
An understandingof formality in quality risk management (see Chapter 5 below) may lead toresources being used more efficiently, where lower risk issues are dealt withvia less formal means, freeing up resources for managing higher risk issues andmore complex problems that may require increased levels of rigour and effort.An understanding of formality can also support risk-based decision-making,where the level of formality that is applied may reflect the degree ofimportance of the decision, as well as the level of uncertainty, complexity andcriticality which may be present.
了解质量风险管理中的正式性（见下文第5章）可能导致更有效地利用资源，通过不太正式的手段处理风险较低的问题，从而腾出资源来管理高风险问题和可能需要更高程度的严谨性和努力的更复杂问题。对形式性的理解也可以支持基于风险的决策，其中所采用的形式化程度可能反映决策的重要性程度，以及可能存在的不确定性、复杂性和关键性水平。
Appropriate use ofquality risk management can facilitate but does not obviate industry’sobligation to comply with regulatory requirements and does not replaceappropriate communications between industry and regulators. Quality riskmanagement should not be used in a manner where decisions are made that justifya practice that would otherwise, in accordance with official guidance and/orregulations, be deemed unacceptable.
适当使用质量风险管理可以促进但并不能免除行业遵守监管要求的义务，也不会取代行业与监管机构之间的适当沟通。质量风险管理的使用方式不应使所作出的决定证明根据官方指导和/或条例被视为不可接受的做法是合理的。
2. SCOPE
范围
This guidelineprovides principles and examples of tools for quality risk management that canbe applied to different aspects of pharmaceutical quality. These aspectsinclude development, manufacturing, distribution, and the inspection and submission/reviewprocesses throughout the lifecycle of drug substances, drug (medicinal)products, biological and biotechnological products (including the use of rawmaterials, solvents, excipients, packaging and labeling materials in drug(medicinal) products, biological and biotechnological products).
本指南提供了质量风险管理工具的原则和示例，可应用于药品质量的不同方面。这些方面包括活性成分、药物（医疗）产品、生物和生物技术产品（包括原料、溶剂、辅料、药品（医疗）产品、生物和生物技术产品中原料、溶剂、辅料、包装和标签材料的使用）整个生命周期的开发、制造、分销以及检验和提交/审查过程。
3. PRINCIPLES OFQUALITY RISK MANAGEMENT
质量风险管理的原则
Two primaryprinciples of quality risk management are:
质量风险管理的两个主要原则是：
The evaluations ofthe risk to quality should be based on scientific knowledge and ultimately linkto the protection of the patient. (Note: Risk to quality includes situationswhere product availability may be impacted, leading to potential patient harm.)
对质量风险的评估应基于科学知识，并最终与保护患者联系起来。（注意：质量风险包括产品可用性受到影响导致潜在患者伤害的情况。
The level ofeffort, formality and documentation of the quality risk management processshould be commensurate with the level of risk.
质量风险管理过程的努力程度、形式和文件应与风险水平相称。
4. GENERAL QUALITYRISK MANAGEMENT PROCESS
一般质量风险管理流程
Quality riskmanagement is a systematic process for the assessment, control, communicationand review of risks to the quality of the drug (medicinal) product across theproduct lifecycle. A model for quality risk management is outlined in thediagram (Figure 1). Other models could be used. The emphasis on each componentof the framework might differ from case to case but a robust process willincorporate consideration of all the elements at a level of detail that iscommensurate with the specific risk.
质量风险管理是一个系统的过程，用于评估，控制，沟通和审查整个产品生命周期中药物（药用）产品质量的风险。图中概述了质量风险管理模型（图1）。可以使用其他模型。对框架每个组成部分的强调可能因具体情况而异，但一个强有力的进程将纳入对所有要素的审议，其详细程度应与具体风险相称。
Figure 1: Overview of a typical quality riskmanagement process
图1：典型质量风险管理流程概述
Decision nodes arenot shown in the diagram above because decisions can occur at any point in theprocess. These decisions might be to return to the previous step and seekfurther information, to adjust the risk models or even to terminate the riskmanagement process based upon information that supports such a decision. Note:“unacceptable” in the flowchart does not only refer to statutory, legislativeor regulatory requirements, but also to the need to revisit the risk assessmentprocess.
上图中未显示决策节点，因为决策可能发生在流程中的任何时间点。这些决定可能是回到上一步并寻求进一步的信息，调整风险模型，甚至根据支持此类决定的信息终止风险管理过程。注：流程图中的"不可接受"不仅涉及法定、立法或监管要求，还涉及重新审查风险评估过程的需要。
4.1 Responsibilities
责任
Quality riskmanagement activities are usually, but not always, undertaken byinterdisciplinary teams. When teams are formed, they should include expertsfrom the appropriate areas (e.g., quality unit, business development,engineering, regulatory affairs, production operations, sales and marketing,supply chain, legal, statistics and clinical) in addition to individuals whoare knowledgeable about the quality risk management process.
质量风险管理活动通常（但并非总是）由跨学科团队进行。当团队成立时，除了了解质量风险管理流程的个人外，他们还应包括来自相应领域（例如，质量部门，业务开发，工程，法规注册，生产运营，销售，供应链，法律，统计和临床）的专家。
Subjectivity canimpact every stage of a quality risk management process, especially theidentification of hazards and estimates of their probabilities of occurrence,the estimation of risk reduction and the effectiveness of decisions made fromquality risk management activities. Subjectivity can be introduced in qualityrisk management through differences in how risks are assessed and in howhazards, harms and risks are perceived by different stakeholders.
主观性可以影响质量风险管理过程的每个阶段，特别是危害的识别和对其发生概率的估计，风险降低的估计以及质量风险管理活动所作决策的有效性。主观性由利益相关者对风险的评估方式的不同以及危害、伤害和风险的感知方式的差异引入质量风险管理中。
Subjectivity canalso be introduced through the use of tools with poorly designed risk scoringscales. While subjectivity cannot be completely eliminated from quality riskmanagement activities, it may be controlled by addressing bias, the proper useof quality risk management tools and maximising the use of relevant data andsources of knowledge (see ICH Q10, Section II.E.1).
主观性也可以通过使用设计不良的风险评分表工具引入。虽然主观性不能从质量风险管理活动中完全消除，但可以通过解决偏见，正确使用质量风险管理工具以及最大限度地使用相关数据和知识来源来控制主观性（见ICH Q10，第II.E.1节）。
All participantsinvolved with quality risk management activities should acknowledge,anticipate, and address the potential for subjectivity.
所有参与质量风险管理活动的参与者都应承认、预测并解决主观性的可能性。
Decision makersshould
决策者应
takeresponsibility for coordinating quality risk management across variousfunctions and departments of their organization; and
负责协调其组织各个职能部门和部门的质量风险管理;和
assure that aquality risk management process is defined, deployed and reviewed and thatadequate resources and knowledge are available;
确保质量风险管理流程已经制定、实施与回顾，并配置有足够的资源和知识可用。
assure thatsubjectivity in quality risk management activities is controlled and minimised,to facilitate scientifically robust risk-based decision making.
确保质量风险管理活动的主观性得到控制并最小化，以促进基于风险的决策更加科学稳健（robust）。
4.2 Initiating aQuality Risk Management Process
启动风险管理流程
Quality riskmanagement 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 processmight include the following:
质量风险管理包括一些系统化流程，设计这些流程是用于协调、促进和改善基于科学的有关风险的决策。启动和策划质量风险管理的步骤可包括：
Define the problemand/or risk question, including pertinent assumptions identifying the potentialfor risk;
明确问题和/或风险疑问，包括识别潜在风险的相关假设；
Assemblebackground information and/ or data on the potential hazard, harm or humanhealth impact relevant to the risk assessment;
收集与风险评估相关的潜在危害源、危害或影响人类健康的背景信息和/或数据；
Identify a leaderand necessary resources;
确定负责人和必要的资源；
Specify atimeline, deliverables and appropriate level of decision making for the riskmanagement process.
规定风险管理流程的时限、交付成果和适当的决策层级。
4.3 RiskAssessment
风险评估
Risk assessmentconsists of the identification of hazards and the analysis and evaluation ofrisks associated with exposure to those hazards (as defined below). Qualityrisk assessments begin with a well-defined problem description or riskquestion. When the risk in question is well defined, an appropriate riskmanagement tool (see examples in Section 5) and the types of information neededto address the risk question will be more readily identifiable. As an aid toclearly defining the risk(s) for risk assessment purposes, three fundamentalquestions are often helpful:
风险评估包括对危害源的识别，并分析和评价暴露于相应危害源的风险。质量风险评估从明确的问题描述或风险疑问开始，当明确定义所讨论的风险后，更容易识别适当的风险管理工具(见第5节中的示例)，以及解决问题所需的信息类型。在风险评估中，以下三个基本问题通常可以帮助清晰地定义风险：
What might gowrong?
1、什么可能出错？
What is thelikelihood (probability) it will go wrong?
2、出错的可能有多大（可能性）？
What are theconsequences (severity)?
3、后果是什么（严重性）？
Hazardidentification is a systematic use of information to identify hazards referringto the risk question or problem description. Information can include historicaldata, theoretical analysis, informed opinions, and the concerns ofstakeholders. Hazard identification addresses the “What might go wrong?”question, including identifying the possible consequences. This provides thebasis for further steps in the quality risk management process.
危害源识别指依据风险疑问或问题描述，系统地运用信息来识别危害源。信息可包括历史数据、理论分析、专业观点和利益相关方的关注点等。风险识别关注“什么可能出错”，包括识别可能的后果，为后续的质量风险管理过程奠定基础。
Risk analysis isthe estimation of the risk associated with the identified hazards. It is thequalitative or quantitative process of linking the likelihood of occurrence andseverity of harms. In some risk management tools, the ability to detect theharm (detectability) also factors in the estimation of risk.
风险分析是对所识别危害源的相关风险进行估计，是将危害发生可能性和严重性相结合的定性或定量过程。在某些风险管理工具中，对危害的检测能力（可检出性detectability）也是估计风险的一个因素。
Risk evaluationcompares the identified and analyzed risk against given risk criteria. Riskevaluations consider the strength of evidence for all three of the fundamentalquestions.
风险评价是将已经识别和分析的风险与给定的可接受标准进行比较。风险评价要综合考虑上述三个基本问题的证据力度。
In doing aneffective risk assessment, the robustness of the data set is important becauseit determines the quality of the output. Revealing assumptions and reasonablesources of uncertainty will enhance confidence in this output and/or helpidentify its limitations. Uncertainty is due to combination of incompleteknowledge about a process and its expected or unexpected variability. Typicalsources of uncertainty include gaps in knowledge gaps in pharmaceutical scienceand process understanding, sources of harm (e.g., failure modes of a process,sources of variability), and probability of detection of problems.
在进行有效的风险评估时，数据的可靠程度非常重要，其决定了评估结果的质量。对假设及不确定性的合理来源的揭示，可以增加风险评估结果的可信度和/或有助于识别该结果的局限性。不确定性是由于工艺知识的不完整和工艺中存在预期或非预期波动的共同作用所致，其典型来源包括制药科学知识局限和工艺理解的差距、危害的来源（如工艺失败模式，波动来源）和检出问题的可能性。
The output of arisk assessment is either a quantitative estimate of risk or a qualitativedescription of a range of risk. When risk is expressed quantitatively, anumerical probability is used. Alternatively, risk can be expressed usingqualitative descriptors, such as “high”, “medium”, or “low”, which should bedefined in as much detail as possible. Sometimes a "risk score" isused to further define descriptors in risk ranking. In quantitative riskassessments, a risk estimate provides the likelihood of a specific consequence,given a set of risk-generating circumstances. Thus, quantitative riskestimation is useful for one particular consequence at a time. Alternatively,some risk management tools use a relative risk measure to combine multiplelevels of severity and probability into an overall estimate of relative risk.The intermediate steps within a scoring process can sometimes employquantitative risk estimation.
风险评估结果可以是风险的定量估计，也可以是风险的定性描述。当定量表达风险时，可用数值表示，当定性描述风险时，如用“高”、“中”、“低”来表述，应尽可能详细地定义。在风险分级中有时使用“风险评分”进一步定义风险等级。当一系列风险产生时，采用定量法进行风险评估，可估计某一特定后果的可能性。因此，风险定量估计对特定后果进行逐一估计时是有用的。另外，也可使用一些风险管理工具把多个水平的风险严重性和可能性组合到一个总的估计中，给出一个相对风险度量。评分过程的中间步骤有时可以使用定量风险估计。
4.4 Risk Control
风险控制
Risk controlincludes decision making to reduce and/or accept risks. The purpose of riskcontrol is to reduce the risk to an acceptable level. The amount of effort usedfor 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.
风险控制包括降低风险和/或接受风险的决策。风险控制的目的是降低风险至可接受水平。风险控制所采取的措施应当与该风险的重要程度相适应。决策者可采用包括收益成本分析在内的不同方法来理解最佳的风险控制水平。
Risk control mightfocus on the following questions:
风险控制可能会关注以下问题：
Is the risk abovean acceptable level?
风险是否高于可接受水平？
What can be doneto reduce or eliminate risks?
什么措施可以用来降低或消除风险？
What is theappropriate balance among benefits, risks and resources?
什么是利益、风险和资源间合适的平衡点？
Are new risksintroduced as a result of the identified risks being controlled?
控制所识别风险时是否会引入新的风险？
Risk reductionfocuses on processes for mitigation or avoidance of quality risk when itexceeds a specified (acceptable) level (see Fig. 1). Risk reduction mightinclude actions taken to mitigate the severity and probability of harm.Processes that improve the detectability of hazards and quality risks mightalso be used as part of a risk control strategy. The implementation of riskreduction measures can introduce new risks into the system or increase thesignificance of other existing risks. Hence, it might be appropriate to revisitthe risk assessment to identify and evaluate any possible change in risk afterimplementing a risk reduction process.
风险降低是指当风险超出规定的（可接受）水平时（见图1），减轻或避免质量风险的过程。风险降低可包括减少危害的严重性和发生的可能性所采取的措施。改善危害源及质量风险可检测性的过程也可作为风险控制策略的一部分。风险降低措施的实施可能会在系统中引入新的风险，或者增加其它已知风险的重要程度。因此，在实施风险降低过程后，可能需要重新回顾（revisit）原有风险评估，以识别和评价风险可能产生的变化。
Risk acceptance isa decision to accept risk. Risk acceptance can be a formal decision to acceptthe residual risk or it can be a passive decision in which residual risks arenot specified. For some types of harms, even the best quality risk managementpractices might not entirely eliminate risk. In these circumstances, it might beagreed that an appropriate quality risk management strategy has been appliedand that quality risk is reduced to a specified (acceptable) level. This(specified) acceptable level will depend on many parameters and should bedecided on a case-by-case basis.
风险接受是指接受风险的决策。风险接受可以是一个接受剩余风险的正式决策，或者是当剩余风险不明确时被动接受的决策。对于某些类型的危害，即使最好的质量风险管理实践活动（practices）也未必能完全消除风险。这种情况下，可认为已采用了适宜的质量风险管理策略，并且质量风险已降低到规定的（可接受的）水平。（规定的）可接受的水平取决于多种因素，需具体情况具体判定。
4.5 RiskCommunication
风险沟通
Risk communicationis the sharing of information about risk and risk management between thedecision makers and others. Parties can communicate at any stage of the riskmanagement process (see Fig. 1: dashed arrows). The output/result of thequality risk management process should be appropriately communicated anddocumented (see Fig. 1: solid arrows). Communications might include those amonginterested parties; e.g., regulators and industry, industry and the patient,within a company, industry or regulatory authority, etc. The includedinformation might relate to the existence, nature, form, probability, severity,acceptability, control, treatment, detectability or other aspects of risks toquality. Communication need not be carried out for each and every riskacceptance. Between the industry and regulatory authorities, communicationconcerning quality risk management decisions might be effected through existingchannels as specified in regulations and guidances.
风险沟通是指在决策者和其它人员之间就有关风险和风险管理的信息进行交流。各方可以在风险管理过程任何阶段进行沟通(见图1的虚线箭头)。质量风险管理过程的输出/结果应当进行适当的沟通并记录(见图1的实线箭头)。沟通可能包括以下相关方：例如，监管者和制药行业之间、制药企业和患者之间，或者在公司、行业和监管机构内部等。沟通所包含的信息可能与质量风险的存在、性质、形式、可能性、严重性、可接受性、控制、处理、可检出性或其它方面相关。无需对每项风险的接受进行沟通。在行业和监管机构之间，可以通过法规和指南中规定的途径沟通有关质量风险管理决策。
4.6 Risk Review
风险回顾(RiskReview)
Risk managementshould be an ongoing part of the quality management process. A mechanism toreview or monitor events should be implemented.
风险管理应当是质量管理过程中的一个持续的活动。应当建立对事件回顾和监控的机制。
The output/resultsof the risk management process should be reviewed to take into account newknowledge and experience. Once a quality risk management process has beeninitiated, that process should continue to be utilized for events that mightimpact the original quality risk management decision, whether these events areplanned (e.g., results of product review, inspections, audits, change control)or unplanned (e.g., root cause from failure investigations, recall). Thefrequency of any review should be based upon the level of risk. Risk reviewmight include reconsideration of risk acceptance decisions (section 4.4).应当考虑最新的知识和经验对风险管理过程中的输出结果进行回顾。当启动质量风险管理流程后，应当将该流程持续用于可能影响初始质量风险管理决策的事件，无论这些事件是计划内（例如，产品回顾、检查、审计、变更控制的结果）或计划外（例如，失败事件调查、召回的根本原因）。风险回顾的频率应当取决于风险水平。风险回顾可能包括重新考虑风险接受的决策(4.4节)。
5. RISKMANAGEMENT METHODOLODY
风险管理方法
Quality riskmanagement supports a scientific and practical approach to decision-making. Itprovides documented, transparent and reproducible methods to accomplish stepsof the quality risk management process based on current knowledge aboutassessing the probability, severity and sometimes detectability of the risk.
质量风险管理支持科学和切合实际的决策方法。质量风险管理提供了文件化、透明化和可重复的方法以实施质量风险管理流程的各个步骤，该方法基于现有知识评估风险的可能性、严重性，有时包括可检出性。
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 ofobservations, trends and other information. Such approaches continue to provideuseful information that might support topics such as handling of complaints,quality defects, deviations and allocation of resources.
传统上，对质量风险的评估和管理是基于多种非正式的方法（经验，和/或内部），如缺陷项、趋势及其它信息的汇总。这些方法对支持投诉处理、质量缺陷、偏差和分配资源等可以继续提供有用的信息。
Additionally, thepharmaceutical industry and regulators can assess and manage risk usingrecognized risk management tools and/ or internal procedures (e.g., standardoperating procedures). Below is a non-exhaustive list of some of these tools(further details in Annex 1 and chapter 8):
此外，制药行业和监管机构可以使用公认的风险管理工具，或者内部程序（如标准操作规程）来评估和管理风险。下面列举了部分工具（详见附录1和第8章中介绍）：
Basic riskmanagement facilitation methods (flowcharts, check sheets etc.);
基本风险管理引导（facilitation）方法(流程图，检查表等)；
Failure ModeEffects Analysis (FMEA);
失效模式与影响分析(FMEA)；
Failure Mode,Effects and Criticality Analysis (FMECA);
失效模式、影响与关键性分析(FMECA)；
Fault TreeAnalysis (FTA);
故障树分析(FTA)；
Hazard Analysisand Critical Control Points (HACCP);
危害源分析及关键控制点(HACCP)；
Hazard OperabilityAnalysis (HAZOP);
危害源及可操作性分析(HAZOP)；
Preliminary HazardAnalysis (PHA);
初步危害源分析(PHA)；
Risk ranking andfiltering;
风险排序及筛选；
Supp ortingstatistical tools.
支持性统计工具。
It might beappropriate to adapt these tools for use in specific areas pertaining to drugsubstance and drug (medicinal) product quality. Quality risk management methodsand the supporting statistical tools can be used in combination (e.g., ProbabilisticRisk Assessment). Combined use provides flexibility that can facilitate theapplication of quality risk management principles.
上述工具可适用于原料药和制剂（医疗产品）质量等相关的特定领域。质量风险管理方法和支持性统计工具可以组合使用（例如概率风险评估）。这些工具的组合使用有助于质量风险管理原则的灵活应用。
The degree ofrigor and formality of quality risk management should reflect availableknowledge and be commensurate with the complexity and/ or criticality of theissue to be addressed.
质量风险管理的正式程度和形式应反映出现有的知识水平，并与需要解决问题的复杂性和/或关键性相匹配。
5.1 Formality inQuality Risk Management
质量风险管理的正式性
Formality inquality risk management is not a binary concept (i.e. formal/informal); varyingdegrees of formality may be applied during quality risk management activities,including when making risk-based decisions. In this way, formality can be considereda continuum (or spectrum), ranging from low to high.
质量风险管理中的正式性不是二元概念（即正式/非正式），在质量风险管理活动期间，包括在做出基于风险的决策时，其正式性的程度可能有多种水平，其从低到高是一个连续范围（或范围）。
When determininghow much formality to apply to a given quality risk management activity,certain factors may be considered. These may include, for example, thefollowing:
对一个给定的质量风险管理活动，当考虑采用正式性的高低程度时，可以考虑以下方面，例如：
Uncertainty: Theterm “uncertainty” in quality risk management means lack of knowledge aboutrisks. The level of uncertainty that is associated with the area being riskassessed informs how much formality may be required to manage potential risks.Systematic approaches for acquiring, analysing, storing and disseminatingscientific information are essential for generating knowledge, which in turn informsall quality risk management activities. Uncertainty may be reduced viaeffective knowledge management, which enables accumulated and new information(both internal and external) to be used to support risk-based decisionsthroughout the lifecycle.
不确定性：质量风险管理中的“不确定性”意味着对相关风险的了解较少。风险评估范围相关的不确定性水平显示了管理潜在风险可能需要的正式性的高低程度。系统地获取、分析、储存和传播科学信息的方法对于产生知识至关重要，而知识反过来又为所有质量风险管理活动提供信息。通过有效的知识管理，可以减少不确定性，从而在整个生命周期中使用积累的和新的信息（内部和外部）来支持基于风险的决策。
Importance: Themore important a risk-based decision is, the higher the level of formality thatshould be applied, and the greater the need to reduce the level of uncertaintyassociated with it.
重要性：基于风险的决策越重要，应采用的正式性的程度越高，就更需要减少与其相关的不确定性水平。
Complexity: Themore complex a process or subject area is to a quality risk managementactivity, the higher the level of formality that should be applied to assureproduct quality.
复杂性：质量风险管理活动的过程或专业领域越复杂，为确保产品质量应采用的正式性的程度就越高。
In general, higherlevels of uncertainty, importance or complexity require more formal qualityrisk management approaches to manage potential risks and to support effectiverisk-based decision making.
一般来说，更高的不确定性、重要性或复杂性需要更为正式的质量风险管理方法来管理潜在风险并支持更有效的基于风险的决策。
The overallapproach for determininghow much formality toapply during quality riskmanagement activities should be described within the quality system. Resourceconstraints should not be used to justify the use of lower levels of formalityin the quality risk management process. Regardless of how much formality isapplied, the robust management of risk is the goal of the process. This shouldbe based on evidence, science and knowledge, where risk scores, ratings orassessments are supported by data or by an appropriate justification orrationale.
应在质量体系中明确描述在质量风险管理活动中应用的正式性程度的总体方法。资源的限制不应被用来证明在质量风险管理过程中使用较低级别的正式性是合理的。过程中无论采用了多么正式的形式，其目标是稳健的风险管理。应以证据、科学和知识为基础，其中风险评分、评级或评估由数据或适当的理由支持。
The following maybe characteristics of higher levels of formality:
较高的正式性程度可能具有以下特征：
All parts of thequality risk management process (Risk Assessment, Risk Control, Risk Review andRisk Communication) are explicitly performed, and stand-alone quality riskmanagement reports (or related documents) which address all aspects of theprocess may be generated and are documented (e.g., within the quality system).
明确执行质量风险管理过程的所有部分（风险评估、风险控制、风险审核和风险沟通），可生成涉及过程所有方面的独立质量风险管理报告（或相关文件），并形成文件（例如，在质量体系内）。
Recognized orother quality risk management tools are used in some or all parts of the process.
在过程的某些或所有部分使用公认的或其他质量风险管理工具。
A cross-functionalteam is assembled for the quality risk management activity. Use of a trainedquality risk management facilitator may be integral to a higher formalityprocess.
为质量风险管理活动组建了一个跨部门的团队。使用经过培训的质量风险管理专家可能是较高正式性的流程所不可或缺的。
The following maybe characteristics of lower levels of formality:
较低的正式性程度可能具有以下特征：
One or more partsof the quality risk management process are not performed as stand-aloneactivities but are addressed within other elements of the quality system whichmay have risk assessment and risk control activities embedded within them.
一个或多个部分的质量风险管理过程不是作为独立活动执行的，而是在质量体系的其他要素中处理的，可能包含风险评估和风险控制活动。
Recognized orother quality risk management tools might not be used in some or all parts ofthe process. A cross functional team might not be necessary.
质量风险管理流程的某些或所有部分可能不会使用公认的或其他质量风险管理工具，可能不需要跨部门团队。
Stand-alonequality risk management reports might not be generated. The outcome of thequality risk management process is usually documented in the relevant parts ofthe quality system.
质量风险管理过程的结果通常记录在质量体系的相关部分中，可能不会生成独立的质量风险管理报告。
Note: Degrees offormality between the above higher and lower levels also exist and may be used.
注：在上述较高与较低级别之间可能还存在一些级别，这些正式性程度也可以使用。
5.2 Risk-basedDecision Making
基于风险的决策
Risk-baseddecision making is inherent in all quality risk management activities; itprovides an essential foundation for decision makers in an organization.Effective risk-based decision making begins with determining the level ofeffort, formality and documentation that should be applied during the qualityrisk management process. The outputs of quality risk management activitiesinclude decisions in relation to what hazards exist, the risks associated withthose hazards, the risk controls required, the acceptability of the residualrisk after risk controls, the communication and review of quality riskmanagement activities and outputs.
基于风险的决策是所有质量风险管理活动中特有的，它为机构中的决策者提供了必要的基础。有效的基于风险的决策始于对质量风险管理过程实施的深度、正式性程度和文件化程度的确定。质量风险管理活动的输出包括存在的危害、与这些危害相关的风险、所需的风险控制、风险控制后剩余风险的可接受性、质量风险管理活动和输出的沟通和审核有关的决策。
Approaches torisk-based decision-making are beneficial, because they address uncertaintythrough the use of knowledge, facilitating informed decisions by regulators andthe pharmaceutical industry in a multitude of areas, including when allocatingresources. They also help recognize where uncertainty remains, so thatappropriate risk controls (including improved detectability) may be identifiedto enhance understanding of those variables and further reduce the level ofuncertainty.
基于风险的决策方法是有益的，因为可以通过使用知识解决不确定性，促进监管部门和制药行业在多个领域做出有依据的决策，包括在分配资源时。也有助于识别仍然存在不确定性的地方，以便确定适当的风险控制（包括提高的可检测性），以加强对这些可变因素的理解，并进一步降低不确定性水平。
As all decisionmaking relies on the use of knowledge, see ICH Q10 for guidance in relation toKnowledge Management. It is important also to ensure the integrity of the datathat are used for risk-based decision making.
由于所有决策都依靠于知识的使用，请参见ICH Q10以获取有关知识管理的指导。确保用于基于风险的决策的数据的完整性也很重要。
Approaches torisk-based decision-making:
基于风险的决策方法：
There aredifferent processes that may be used to make risk-based decisions; these aredirectly related to the level of formality that is applied during the qualityrisk management process. (See Section 5.1 above for guidance on whatconstitutes formality in quality risk management.) In general, higher levels offormality in quality risk management require higher levels of structure inrelation to risk-based decision making. There can be varying degrees ofstructure with regard to approaches for risk-based decision making. Thesedegrees of structure can be considered to be on a continuum (or spectrum).Below are descriptions for highly structured vs. less structured processes, andfor rule-based processes when making risk-based decisions:
做出基于风险的决策的可以用不同的流程，这些与质量风险管理过程中采用的正式性程度直接相关。（关于质量风险管理正式性的构成，请参见上文第5.1节。）一般来说，质量风险管理中较高的正式性程度要求较高的基于风险的决策结构。基于风险的决策方法可能存在多种程度的结构。这些程度的结构可以被认为是一个连续体（或范围）。以下是对高度结构化流程与较低结构化流程，以及在做出基于风险的决策时基于规则的流程的描述：
Some risk-baseddecision making processes are highly structured and can involve a formalanalysis of the available options that exist before making a decision. Theyinvolve an in-depth consideration of relevant factors associated with theavailable options. Such processes might be used when there is a high degree ofimportance associated with the decision, and when the level of uncertaintyand/or complexity is high.
一些基于风险的决策过程是高度结构化的，在做出决策之前，可以对现有的可用选项进行正式分析，它们涉及对与可用选项相关因素的深入考虑。当决策非常重要，同时不确定性和/或复杂性水平较高时，可使用此类流程。
Other risk-baseddecision making processes are less structured; here, simpler approaches areused to arrive at decisions, and they primarily make use of existing knowledgeto support an assessment of hazards, risks and any required risk controls. Suchprocesses might still be used when there is a high degree of importanceassociated with the decision, but the degree of uncertainty and/or complexityis lower.
其他基于风险的决策过程是较低结构化的流程，使用更简单的方法做出决策，它们主要利用现有知识支持对危害源、风险和任何必要的风险控制进行评估。当决策非常重要，但不确定性和/或复杂性较低时，仍可使用此类过程。
Decisions mightalso be made using rule-based (or standardised) approaches, which do notrequire a new risk assessment to make such decisions. This is where there areSOPs, policies or well understood requirements in place which determine whatdecisions must be made. Here, rules (or limits) may be in place which governsuch decisions; these may be based on a previously obtained understanding ofthe relevant risks and they usually lead to predetermined actions or expectedoutcomes.
可以使用基于规程（或标准化）的方法做出决策，这些方法不需要新的风险评估来做出此类决策，这就是在有SOP、政策或充分理解需求的地方，就已经决定了必须做出何种决策。同样可能存在管理此类决策的规程（或限制），可能基于先前对相关风险的了解，通常会导致预定的行动或预期结果。
6. INTEGRATIONOF QUALITY RISK MANAGEMENT INTO INDUSTRY AND REGULATORY OPERATIONS
质量风险管理在制药行业和监管机构的应用
Quality riskmanagement is a process that supports science-based and practical decisionswhen integrated into quality systems (see Annex II). As outlined in theintroduction, appropriate use of quality risk management does not obviateindustry’s obligation to comply with regulatory requirements. However,effective quality risk management can facilitate better and more informeddecisions, can provide regulators with greater assurance of a company’s abilityto deal with potential risks, and might affect the extent and level of directregulatory oversight. In addition, quality risk management can facilitatebetter use of resources by all parties.
质量风险管理融入质量体系时，它是一个支持基于科学、切实可行决策的过程（见附录Ⅱ）。如前言所述，合理使用质量风险管理不能免除制药行业遵守法规要求的义务。然而，有效的质量风险管理可以促进更全面和更合理的决策，对于企业处理潜在风险的能力，给予监管机构更多的信心并可能影响到其监管的范围和程度，同时质量风险管理可以促进各方更好地利用资源。
Training of bothindustry and regulatory personnel in quality risk management processes providesfor greater understanding of decision-making processes and builds confidence inquality risk management outcomes.
对制药行业和监管机构人员进行质量风险管理的培训有利于他们加深对决策过程的理解，建立对质量风险管理结果的信心。
Quality riskmanagement should be integrated into existing operations and documentedappropriately. While manufacturing and supply chain diversity can be enablersof product availability, increasingly complex supply chains lead tointerdependencies that can introduce systemic quality/manufacturing risksimpacting supply chain robustness. Application of quality risk management canproactively mitigate these risks. Preventive measures supporting productavailability may be identified through quality risk management activities.
质量风险管理应当整合到现有操作中并恰当记录。虽然生产和供应链的多样性可以成为产品可及性的推进器，但日益复杂的供应链会导致相互依赖，从而引入影响供应链稳健性的整体质量/生产风险。采用质量风险管理可以积极主动地减轻这些风险，可通过质量风险管理活动来找到支持产品可及性的预防措施。
Annex II providesexamples of situations in which the use of the quality risk management processmight provide information that could then be used in a variety ofpharmaceutical operations. These examples are provided for illustrativepurposes only and should not be considered a definitive or exhaustive list.These examples are not intended to create any new expectations beyond therequirements laid out in the current regulations.
附录Ⅱ提供了一些适用于制药行业质量风险管理的示例。这些示例仅供参考，并非最佳（definitive）或详尽的列举，也没有提出超越现行法规的要求。
Examples forindustry and regulatory operations (see Annex II):
质量风险管理在制药行业和药品监管机构的应用示例（见附录Ⅱ）：
Quality management.
质量管理。
Examples for industry operationsand activities (see Annex II):
质量风险管理在制药行业运行中的应用示例（见附录Ⅱ）：
Development;
研发；
Facility, equipment and utilities;
厂房、设备和设施；
Materials management;
物料管理；
Production;
生产；
Laboratory control and stability testing;
实验室控制和稳定性试验；
Packaging and labeling;
包装和贴签。
Supply Chain Control.
供应链控制
Examples for regulatory operations(see Annex II):
质量风险管理在药品监管中的应用示例（见附录Ⅱ）：
Inspection and assessment activities.
检查与评估工作。
While regulatorydecisions will continue to be taken on a regional basis, a common understandingand application of quality risk management principles could facilitate mutualconfidence and promote more consistent decisions among regulators on the basisof the same information. This collaboration could be important in thedevelopment of policies and guidelines that integrate and support quality riskmanagement practices.
尽管监管决策仍将在各自监管区域内进行，对质量风险管理原则的共同理解和应用仍有助于增进药品监管机构之间的互信，并促进基于相同信息做出更加一致的决定。这种合作对于制订用于整合并支持质量风险管理实践的政策与指南具有重要意义。
The role ofQuality Risk Management in addressing Product Availability Risks
质量风险管理在应对产品可及性风险中的作用
Quality/manufacturingissues, including non-compliance with Good Manufacturing Practice (GMP), are afrequent cause of product availability issues (e.g., product shortages). Theinterests of patients are served by risk-based drug shortage prevention andmitigation activities that help to proactively manage supply chain complexitiesand ensure availability of needed medicines. An effective pharmaceuticalquality system drives both supply chain robustness and sustainable GMPcompliance. It also uses quality risk management and knowledge management toprovide an early warning system that supports effective oversight and responseto evolving quality/manufacturing risks from the pharmaceutical company or itsexternal partners. The level of formality applied to risk-based drug shortageprevention and mitigation activities may vary (see Chapter 5). Factors that canaffect supply reliability, and hence product availability, include thefollowing:
质量/生产问题，包括药品生产质量管理规范（GMP）不合规（non-compliance）问题，是产品可及性问题（例如药品短缺）的常见原因。基于风险的药品短缺预防和规避活动能够帮助积极主动地管理供应链复杂状况并确保所需药品可及性，以服务于患者的利益。有效的药品质量体系既可以促进供应链稳健性又可以促进GMP持续合规。它还利用质量风险管理和知识管理提供早期预警系统，以支持对制药公司或其外部合作伙伴不断发展变化的质量/生产风险进行有效的监督和响应。基于风险的药品短缺预防和规避工作的正式性程度可有所不同（见第5章）。能够影响供应可靠性，进而影响产品可及性的因素包括：
Manufacturing ProcessVariation and State of Control (internal and external):
生产工艺变化和受控状态（内部和外部）：
Processes thatexhibit excessive variability (e.g., process drift, non-uniformity) havecapability gaps that can result in unpredictable outputs and may adverselyimpact quality, timeliness, yield, and consequently product availability.Quality risk management can help design monitoring systems that are capable ofdetecting departures from a state of control and deficiencies in manufacturingprocesses, so they can be investigated to address root causes.
有着过度变化性（例如工艺漂移、不一致）的工艺在其能力上存在缺陷，这种缺陷可导致不可预测的结果，并可能会给质量、及时性、收率、及后续的产品可及性带来不良影响。质量风险管理可帮助设计出能够检测到受控状态偏离和生产工艺缺陷的监测系统，这样就可以对其进行调查来明确其根本原因。
ManufacturingFacilities:
生产厂房设施：
A robust facilityinfrastructure can facilitate reliable supply; it includes suitable equipmentand well-designed facilities for manufacturing and packaging. Robustness can beaffected by multiple factors, such as an aging facility, insufficientmaintenance or an operational design that is vulnerable to human error. Risksto supply can be reduced by addressing these factors, as well as through use ofmodern technology, such as digitalization, automation, isolation technology,amongst others.
稳固可靠（robust）的厂房基础设施能够促进可靠的供应，包括为生产和包装所选择适宜的设备和设计良好的厂房设施。可靠性（robustness）可受多种因素的影响，包括厂房老化、维护不充分或易导致人员差错的操作设计。可通过解决这些因素，及采用如数字化、自动化、隔离技术等现代技术来降低供应风险。
Oversight ofOutsourced Activities and Suppliers:
外包活动及供应商监督：
Quality systemgovernance includes assuring the acceptability of supply chain partners overthe product lifecycle. Approval and oversight of outsourced activities andmaterial suppliers is informed by risk assessments, effective knowledgemanagement, and an effective monitoring strategy for supply chain partnerperformance. A successful manufacturing partnership is strengthened byappropriate communication and collaboration mechanisms. When substantialvariability is identified in the quality and safety of supplied materials or inthe services provided, enhanced review and monitoring activities are justified(See Section 2.7 of ICH Q10). In some cases, it may be necessary to identify anew supply chain entity (e.g. a pre-qualified backup option) to perform afunction.
质量体系管治（governance）包括在产品生命周期中确保供应链合作伙伴的可接受性。通过风险评估、有效的知识管理和有效的供应链合作伙伴绩效监控策略，对外包活动和物料供应商进行审批和监督。适宜的沟通和合作机制可以加强成功的生产合作伙伴关系，如发现所供应物料或所提供服务的质量和安全方面存在重大的变化时，则需要加强审核和监测工作（见ICH Q10第2.7部分）。在某些情况下，可能需要寻找新的供应链实体（例如经过资质确认的备份供应商）来完成某项职能。
7. DEFINITIONS
术语
Decision Maker(s):Person(s) with the competence and authority to make appropriate and timely qualityrisk management decisions.
决策者：具有能力和职权做出适当和及时的质量风险管理决策的人员。
Detectability: Theability to discover or determine the existence, presence, or fact of a hazard.
可检出性：发现或确定危害源存在、出现或作为事实（fact）的能力。
Harm: Damage tohealth, including the damage that can occur from loss of product quality oravailability.
危害：对健康的损害，包括因产品质量或可及性的缺失而可能造成的损害。
Hazard: Thepotential source of harm (ISO/IEC Guide 51).
危害源：潜在的危害来源(ISO/IEC指南51)。
HazardIdentification: The systematic use of information to identify potential sourcesof harm (hazards) referring to the risk question or problem description.
危害源识别：系统地运用信息识别有关风险疑问或问题描述的潜在危害来源(危害源)。
Product Lifecycle:All phases in the life of the product from the initial development throughmarketing until the product’s discontinuation.
产品生命周期：从最初的研发到上市，直到产品退市整个产品生命的所有阶段。
Quality: Thedegree to which a set of inherent properties of a product, system or processfulfills requirements (see ICH Q6A definition specifically for"quality" of drug substance and drug (medicinal) products.)
质量：产品、系统或工艺的一组固有特性满足要求的程度（见ICH Q6A原料药和制剂（医疗产品）中关于“质量”的具体定义。）
Quality RiskManagement: A systematic process for the assessment, control, communication andreview of risks to the quality of the drug (medicinal) product across theproduct lifecycle.
质量风险管理：在整个产品生命周期中评估、控制、沟通和回顾药品（医疗产品）质量风险的系统化流程。
Quality System: Thesum of all aspects of a system that implements quality policy and ensures thatquality objectives are met.
质量体系：系统实施质量方针并确保实现质量目标的所有方面的总和。
Requirements: Theexplicit or implicit needs or expectations of the patients or their surrogates(e.g., health care professionals, regulators and legislators). In thisdocument, “requirements” refers not only to statutory, legislative, orregulatory requirements, but also to such needs and expectations.
要求：患者或其代理人（如医务人员、监管者和立法者）的明示或隐含需要或期望。在本文件中，"要求"不仅指法律或法规要求，还指此类需要和期望。
Risk: Thecombination of the probability of occurrence of harm and the severity of thatharm (ISO/IEC Guide 51).
风险：危害发生的可能性及其严重性的组合。(ISO/EC指南51)。
Risk Acceptance: Thedecision to accept risk (ISO Guide 73).
风险接受：接受风险的决策(ISO指南73)。
Risk Analysis: Theestimation of the risk associated with the identified hazards.
风险分析：对已识别的危害源相关风险的估计。
Risk Assessment: Asystematic process of organizing information to support a risk decision to bemade within a risk management process. It consists of the identification ofhazards and the analysis and evaluation of risks associated with exposure tothose hazards.
风险评估：组织信息以支持风险管理过程中风险决策的系统化流程。其包含对危害源识别，以及分析和评价接触这些危害源的相关风险。
Risk-based DecisionMaking: An approach or process that considers knowledgeabout risks relevant to the decision and whether risks are at an acceptablelevel.
基于风险的决策：一种考虑了与决策相关风险的知识及风险是否在可接受水平的方法或流程。
RiskCommunication: The sharing of information about risk and risk managementbetween the decision maker and other stakeholders.
风险沟通：决策者和其他风险利益相关方之间分享有关风险和风险管理的信息。
Risk Control: Actionsimplementing risk management decisions (ISO Guide 73).
风险控制：实施风险管理决策的行动(ISO指南73)。
Risk Evaluation: Thecomparison of the estimated risk to given risk criteria using a quantitative orqualitative scale to determine the significance of the risk.
风险评价：用定性或定量尺度对已估计风险与既定风险标准进行比较，以确定风险重要程度。
8. REFERENCES
参考文献
ICH Q8Pharmaceutical Development.
ICH Q10Pharmaceutical Quality System.
ISO/IEC Guide73:2002 - Risk Management - Vocabulary - Guidelines for use in Standards.
ISO/IEC Guide51:2014 - Safety Aspects - Guideline for their inclusion in standards.
IEC 61025 - FaultTree Analysis (FTA).
IEC 60812:2018Failure modes and effects analysis (FMEA and FMECA).
IEC 61882:2016 -Hazard and operability studies (HAZOP studies) – Application guide.
ISO 14971:2019 –Medical devices -Application of risk management to medical devices.
ISO 7870-1:2019 -Control Charts
ISO 7870-4:2021-Cumulative Sum Charts.
ISO 7870-3:2020 -Acceptance Control Charts.
ISO 7870-2:2013 -Shewhart Control Charts.
WHO TechnicalReport Series No 908, 2003, Annex 7 Application of Hazard Analysis and CriticalControl Point (HACCP) methodology to pharmaceuticals.
What is TotalQuality Control?; The Japanese Way, Kaoru Ishikawa (Translated by David
Liu), 1985, ISBN0139524339.
Failure Mode andEffect Analysis, FMEA from Theory to Execution, 2nd Edition 2003, D.
Stamatis, ISBN0873895983.
Process Mapping bythe American Productivity & Quality Center, 2002, ISBN 1928593739.
Parenteral DrugAssociation. Technical Report No. 54 Implementation of quality risk managementfor pharmaceutical and biotechnology manufacturing operations. 2012.
Parenteral DrugAssociation. Points to consider for aging facilities. 2017.
Parenteral DrugAssociation. Technical Report No. 68. Risk-based approach for prevention andmanagement of drug shortages. 2014.
InternationalSociety for Pharmaceutical Engineering. Report on the ISPE Drug shortagessurvey. 2013.
InternationalSociety for Pharmaceutical Engineering. Drug shortages prevention plan. 2014.
Tabersky D,Woelfle M, Ruess J, Brem S, Brombacher S. Recent regulatory trends inpharmaceutical manufacturing and their impact on the industry. CHIMIA,2018;72(3):146-150.
O’Donnell K, TobinD, Butler S, Haddad G, Kelleher D. Understanding the concept of formality inquality risk management. J. Valid. Technol, 2020 Jun; 26(3).
ANNEX I: QUALITYRISK MANAGEMENT METHODS AND TOOLS
附录Ⅰ:质量风险管理方法与工具
The purpose ofthis annex is to provide a general overview of and references for some of theprimary tools that might be used in quality risk management by industry andregulators. The references are included as an aid to gain more knowledge anddetail about the particular tool. This is not an exhaustive list. It isimportant to note that no one tool or set of tools is applicable to everysituation in which a quality risk management procedure is used.
本附录的目的是为制药行业和监管机构提供一些质量风险管理基本工具的概述和参考。这些参考有助于获得某一特定工具的更多知识和细节。本附录给出了部分方法和工具列表。需要说明的是，没有一个或一套工具可以用于质量风险管理流程的每一种情况。
It is neitheralways appropriate nor always necessary to use highly formal quality riskmanagement methods and tools. The use of less formal quality risk managementmethods and tools can also be considered acceptable. See Chapter 5 for guidanceon what constitutes formality in quality risk management.总是使用高度正式的质量风险管理方法和工具既不适宜也不必要。使用不那么正式的质量风险管理方法和工具也是可以的。有关质量风险管理的指南请见第5章。
I.1 Basic RiskManagement Facilitation Methods
风险管理的基本方法
Some of the simpletechniques that are commonly used to structure risk management by organizingdata and facilitating decision-making are:
一些常用的简单技术方法通常是通过组织数据和促进决策来进行质量风险管理，包括：
Flowcharts;
流程图；
Check Sheets;
检查表；
Process Mapping;
过程流程图（Process Mapping）；
Cause and EffectDiagrams (also called an Ishikawa diagram or fish bone diagram).
因果图(也称为石川图或鱼骨图)。
I.2 Failure ModeEffects Analysis (FMEA)
失效模式与影响分析(FMEA)
FMEA (see IEC60812) provides for an evaluation of potential failure modes for processes andtheir likely effect on outcomes and/or product performance. Once failure modesare established, risk reduction can be used to eliminate, contain, reduce orcontrol the potential failures. FMEA relies on product and processunderstanding. FMEA methodically breaks down the analysis of complex processesinto manageable steps. It is a powerful tool for summarizing the importantmodes of failure, factors causing these failures and the likely effects of thesefailures.
FMEA(参见IEC60812)用于评价过程潜在失效模式及其结果和/或产品性能的可能影响。一旦建立了失效模式，就可以采用风险降低措施来消除、限制、降低或控制潜在的失效。FMEA依赖于对产品与过程的理解。FMEA有条理地将复杂流程的分析分解为可操作的一些步骤。在汇总重要的失效模式、引起这些失效的因素以及这些失效带来的可能影响方面，FMEA是一个强有力的工具。
Potential Areas ofUse(s)
潜在应用领域
FMEA can be usedto prioritize risks and monitor the effectiveness of risk control activities.
FMEA可以用于确定风险的优先级并且监测风险控制活动的有效性。
FMEA can beapplied to equipment and facilities and might be used to analyze amanufacturing operation and its effect on product or process. It identifieselements/operations within the system that render it vulnerable. The output/results of FMEA can be used as a basis for design or further analysis or toguide resource deployment.
FMEA可以用于设备与设施，也可用于分析一个生产操作及其对产品和工艺的影响。FMEA可识别出使系统容易出现问题的要素/操作。FMEA的输出/结果可以作为设计或进一步分析或指导资源配置的基础。
I.3 Failure Mode, Effects and CriticalityAnalysis (FMECA)
失效模式、影响与关键性分析(FMECA)
FMEA might beextended to incorporate an investigation of the degree of severity of theconsequences, their respective probabilities of occurrence, and theirdetectability, thereby becoming a Failure Mode Effect and Criticality Analysis(FMECA; see IEC 60812). In order for such an analysis to be performed, theproduct or process specifications should be established. FMECA can identifyplaces where additional preventive actions might be appropriate to minimizerisks.
FMEA可以延伸到包括失效模式后果的严重程度，各自发生的可能性以及其可检出性的调查，从而成为失效模式、影响与关键性分析(FMECA，参见IEC60812)。为了进行该分析，应当建立产品或工艺标准。FMECA可以识别出何处需要采取额外预防措施从而使风险最小化。
Potential Areas ofUse(s)
潜在应用领域
FMECA applicationin the pharmaceutical industry should mostly be utilized for failures and risksassociated with manufacturing processes; however, it is not limited to thisapplication. The output of an FMECA is a relative risk “score” for each failuremode, which is used to rank the modes on a relative risk basis.
FMECA在制药行业里主要用于与生产工艺相关的失效以及风险。然而，它不局限于这方面的应用。FMECA的输出是为每个失效模式给出一个相对风险“分值”，在相对风险的基础上，通过此分值对这些失效模式进行排序。
I.4 Fault Tree Analysis (FTA)
故障树分析(FTA)
The FTA tool (seeIEC 61025) is an approach that assumes failure of the functionality of aproduct or process. This tool evaluates system (or sub-system) failures one ata time but can combine multiple causes of failure by identifying causal chains.The results are represented pictorially in the form of a tree of fault modes.At each level in the tree, combinations of fault modes are described withlogical operators (AND, OR, etc.). FTA relies on the experts’ processunderstanding to identify causal factors.
FTA工具(参见IEC61025)是假设（assume）某一产品或过程的性能失效进行分析的方法。该工具逐一评价系统(或子系统)的失效，也可通过识别因果链，合并考虑引起失效的多种原因。其结果是用树状图将故障模式展现出来。在该树状图的每一层级，是以逻辑算符(“与”、“或”等)对故障模式的组合进行描述的。FTA依赖于专家对过程的理解以识别起因。
Potential Areas ofUse(s)
潜在应用领域
FTA can be used toestablish the pathway to the root cause of the failure. FTA can be used to investigatecomplaints or deviations in order to fully understand their root cause and toensure that intended improvements will fully resolve the issue and not lead toother issues (i.e. solve one problem yet cause a different problem). Fault TreeAnalysis is an effective tool for evaluating how multiple factors affect agiven issue. The output of an FTA includes a visual representation of failuremodes. It is useful both for risk assessment and in developing monitoringprograms.
FTA可以被用来建立失效的根本原因的路径。可以用FTA来调查投诉或偏差以便全面地了解失效的根本原因，并确保预期改进会完全解决该问题，且不会引发其他问题(即，不能解决了一个问题但引起了另一个问题)。故障树分析是一个有效的工具，用于评价多个因素如何影响一个给定问题。FTA输出结果包括对失效模式的可视化表述。它对于风险评估以及制定监测程序都非常有用。
I.5 Hazard Analysis and Critical Control Points(HACCP)
危害源分析及关键控制点(HACCP)
HACCP is asystematic, proactive, and preventive tool for assuring product quality,reliability, and safety (see WHO Technical Report Series No 908, 2003 Annex 7).It is a structured approach that applies technical and scientific principles toanalyze, evaluate, prevent, and control the risk or adverse consequence(s) ofhazard(s) due to the design, development, production, and use of products.
危害源分析和关键控制点是确保产品质量、可靠性及安全性的一种系统的、主动的和预防的工具(参见WHO Technical Report SeriesNo 908，2003Annex7)。它是一种结构化的方法，通过采用技术和科学的原则来分析、评价、预防和控制由于产品的设计、开发、生产和使用所带来的危害源的风险或其不利后果。
HACCP consists ofthe following seven steps:
HACCP由下列七个步骤组成：
(1)conducta hazard analysis and identify preventive measures for each step of theprocess;
对过程每一个步骤的危害源进行分析并确定预防措施；
(2)determinethe critical control points;
确定关键控制点；
(3)establishcritical limits;
建立关键限度；
(4)establisha system to monitor the critical control points;
建立监测关键控制点的系统；
(5)establishthe corrective action to be taken when monitoring indicates that the criticalcontrol points are not in a state of control;
建立当监测显示关键控制点处于非受控状态时应当采取的纠正措施；
(6)establishsystem to verify that the HACCP system is working effectively;
建立能够确证HACCP系统有效运行的系统；
(7)establisha record-keeping system.
建立文件记录系统。
Potential Areas ofUse(s)
潜在应用领域
HACCP might beused to identify and manage risks associated with physical, chemical andbiological hazards (including microbiological contamination). HACCP is mostuseful when product and process understanding is sufficiently comprehensive tosupport identification of critical control points. The output of a HACCP analysisis risk management information that facilitates monitoring of critical pointsnot only in the manufacturing process but also in other life cycle phases.
HACCP可用于有关物理、化学和生物危害源(包括微生物污染)的风险识别及管理。当对产品和工艺的理解足以支持识别关键控制点时，HACCP最为有用。HACCP分析的结果作为风险管理信息，不仅可促进生产过程中关键点监测，也可促进生命周期中其他阶段的关键点监测。
I.6 Hazard Operability Analysis (HAZOP)
危害源及可操作性分析(HAZOP)
HAZOP (see IEC61882) is based on a theory that assumes that risk events are caused bydeviations from the design or operating intentions. It is a systematicbrainstorming technique for identifying hazards using so-called “guide-words”.“Guide-words” (e.g., No, More, Other Than, Part of, etc.) are applied torelevant parameters (e.g., contamination, temperature) to help identifypotential deviations from normal use or design intentions. It often uses a teamof people with expertise covering the design of the process or product and itsapplication.
HAZOP(参见IEC61882)基于一种理论，这种理论假定许多风险事件都是由于偏离了设计意图或正确操作所造成的。它是采用所谓的“引导词”来识别危害源的系统性头脑风暴技术。将“引导词”(如不做、超过、其他方式、部分执行等)用于相关参数(如污染、温度)来帮助识别与正常使用或设计意图之间的潜在偏差。它通常需要一组包括了解工艺或产品设计及其应用等专门技术的人员。
Potential Areas ofUse(s)
潜在应用领域
HAZOP can beapplied to manufacturing processes, including outsourced production andformulation as well as the upstream suppliers, equipment and facilities fordrug substances and drug (medicinal) products. It has also been used primarilyin the pharmaceutical industry for evaluating process safety hazards. As is thecase with HACCP, the output of a HAZOP analysis is a list of critical operationsfor risk management. This facilitates regular monitoring of critical points inthe manufacturing process.
HAZOP可以应用于原料药和制剂(医疗产品)的生产过程，包括委托生产、供应商、设备和设施。在制药行业，它还主要用于评价工艺安全性危害源。与HACCP类似，HAZOP分析的结果列出了风险管理的关键操作，有助于生产过程中关键点的定期监测。
I.7 Preliminary Hazard Analysis (PHA)
初步危害源分析(PHA)
PHA is a tool ofanalysis based on applying prior experience or knowledge of a hazard or failureto identify future hazards, hazardous situations and events that might causeharm, as well as to estimate their probability of occurrence for a givenactivity, facility, product or system. The tool consists of: 1) theidentification of the possibilities that the risk event happens, thequalitative evaluation of the extent of possible injury or damage to healththat could result and 3) a relative ranking of the hazard using a combinationof severity and likelihood of occurrence, and 4) the identification of possibleremedial measures.PHA是一种分析工具，运用之前对某个危害源及失效(failure)所获得的经验或知识，来识别潜在的危害源、危害状态和可能引起损害的事件，并估计其在某个特定的活动、厂房设施、产品或系统中发生的概率。该工具包含：1)确定风险事件发生的可能性，2)对于可能导致的损伤或健康损害程度的定性评价，3)用严重性和发生可能性的组合对危害源进行排序，4)确定可能的补救措施。
Potential Areas ofUse(s)
潜在应用领域
PHA might beuseful when analyzing existing systems or prioritizing hazards wherecircumstances prevent a more extensive technique from being used. It can beused for product, process and facility design as well as to evaluate the typesof hazards for the general product type, then the product class, and finallythe specific product. PHA is most commonly used early in the development of a projectwhen there is little information on design details or operating procedures;thus, it will often be a precursor to further studies. Typically, hazardsidentified in the PHA are further assessed with other risk management toolssuch as those in this section.
在条件不允许采用其他工具时，PHA有助于对已有系统进行分析或确定危害源的优先级。它可应用于产品、工艺与设施设计，还可应用于评价从产品的基本类型，到产品类别，最终到某一具体产品的危害源类型。PHA常用于缺乏详细设计或操作规程方面信息的项目研发初期，并经常作为进一步研究的铺垫。对PHA所确定的危害源，通常会使用本章节中其它的风险管理工具进一步评估。
I.8 Risk Ranking and Filtering
风险排序及筛选
Risk ranking andfiltering is a tool for comparing and ranking risks. Risk ranking of complexsystems typically requires evaluation of multiple diverse quantitative andqualitative factors for each risk. The tool involves breaking down a basic riskquestion into as many components as needed to capture factors involved in therisk. These factors are combined into a single relative risk score that canthen be used for ranking risks. “Filters,” in the form of weighting factors orcut-offs for risk scores, can be used to scale or fit the risk ranking tomanagement or policy objectives.风险排序及筛选是一个用于对风险进行比较和排序的工具。复杂系统的风险排序通常要求评价每个风险的多重多样的定量和定性因素。该工具通常将一个基本的风险问题根据需要分解成尽可能多的组成部分，用于获取风险所涉及的因素。将这些因素整合到一起得到一个相对的分值，该分值可用于风险排序。“筛选工具”可对该分值采用加权因子或限值的形式，使得风险排序与管理或方针目标相适应。
Potential Areas ofUse(s)
潜在的应用领域
Risk ranking andfiltering can be used to prioritize manufacturing sites for inspection/audit byregulators or industry. Risk ranking methods are particularly helpful insituations in which the portfolio of risks and the underlying consequences tobe managed are diverse and difficult to compare using a single tool. Riskranking is useful when management needs to evaluate bothquantitatively-assessed and qualitatively-assessed risks within the sameorganizational framework.
监管机构或制药行业可采用风险排序及筛选来确定生产场地检查或审计的优先级别。当要处理的风险组成及其潜在后果具有多样性并难以用单个工具进行比较时，风险排序的方法尤其有效。当管理层需要在相同的组织框架内部对风险进行定性和定量地评估时，风险排序将非常有用。
I.9 Supporting Statistical Tools
支持性统计学工具
Statistical toolscan support and facilitate quality risk management. They can enable effectivedata assessment, aid in determining the significance of the data set(s), andfacilitate more reliable decision making. A listing of some of the principalstatistical tools commonly used in the pharmaceutical industry is provided:
统计学工具可支持和促进质量风险的管理，使有效的数据评估成为可能，有助于确定数据的显著性，促进更可靠的决策。下面列出了在制药行业常用的一些基本的统计学工具：
Control Charts, for example:
控制图，例如：
Acceptance Control Charts (see ISO7966);
验收控制图(参见ISO7966)；
Control Charts with ArithmeticAverage and Warning Limits (see ISO 7873);
带算数平均值和警戒限的控制图(参见ISO7873)；
Cumulative Sum Charts (see ISO7871);
累积和图(参见ISO7871)；
Shewhart Control Charts (see ISO8258);
休哈特控制图(参见ISO8258)；
Weighted Moving Average.
加权移动平均控制图。
Design of Experiments (DOE);
实验设计(DOE)；
Histograms;
直方图；
Pareto Charts;
帕累托图；
Process Capability Analysis.
工艺能力分析。
ANNEX II:QUALITY RISK MANAGEMENT AS PART OF INTEGRATED QUALITY MANAGEMENT
附录Ⅱ:质量风险管理的潜在应用
This Annex isintended to identify potential uses of quality risk management principles andtools by industry and regulators. However, the selection of particular riskmanagement tools is completely dependent upon specific facts and circumstances.本附录旨在使制药行业和监管机构确定质量风险管理的原则与工具的潜在应用。对于特定风险管理工具的选择完全取决于具体的事实与情况。
These examples areprovided for illustrative purposes and only suggest potential uses of qualityrisk management. This Annex is not intended to create any new expectationsbeyond the current regulatory requirements.本附录所举示例作为解释说明，仅是质量风险管理潜在应用的建议。本附录并未提出超越现行法规的要求。
II.1 Quality Risk Management as Part of IntegratedQuality Management
整体质量管理中的质量风险管理
Documentation
文件
To review currentinterpretations and application of regulatory expectations;
对现行监管期望的解读及应用的回顾；
To determine thedesirability of and/or develop the content for SOPs, guidelines, etc.
确定SOP、指南等的必要性及其内容的撰写。
Training andeducation
培训及教育
To determine theappropriateness of initial and/or ongoing training sessions based on education,experience and working habits of staff, as well as on a periodic assessment ofprevious training (e.g., its effectiveness);
根据员工的教育、经验及工作习惯，以及对其之前培训的定期评估(如有效性)，来确定初始以及持续培训课程是否适合；
To identify thetraining, experience, qualifications and physical abilities that allowpersonnel to perform an operation reliably and with no adverse impact on thequality of the product.
确认人员的培训、经验、资质以及体能确实能够胜任某项操作，且不会对产品质量带来负面影响。
Quality defects
质量缺陷
To provide thebasis for identifying, evaluating, and communicating the potential qualityimpact of a suspected quality defect, complaint, trend, deviation,investigation, out of specification result, etc;为识别、评价和沟通某一疑似质量缺陷、投诉、趋势、偏差、调查、OOS结果等的潜在质量影响提供依据；
To facilitate riskcommunications and determine appropriate action to address significant productdefects, in conjunction with regulatory authorities (e.g., recall).与监管机构一起，在处理重大产品缺陷时，促进风险沟通并确定适当的措施（如召回）。
Auditing/Inspection
审计/检查
To define thefrequency and scope of audits, both internal and external, taking into accountfactors such as:
确定内外部审计的频率和范围时，考虑如下因素：
Existing legalrequirements;
现行法律要求；
Overall compliancestatus and history of the company or facility;
公司或工厂整体的合规状态及历史；
Robustness of acompany’s quality risk management activities;
公司质量风险管理活动的稳健性(Robustness)；
Complexity of thesite;
场地的复杂性；
Complexity of themanufacturing process;
生产工艺的复杂性；
Complexity of theproduct and its therapeutic significance;
产品的复杂性及其临床治疗意义；
Number andsignificance of quality defects (e.g., recall);
质量缺陷(如召回)的数量及重要性；
Results ofprevious audits/inspections;
以往的审计/检查结果；
Major changes ofbuilding, equipment, processes, key personnel;
厂房、设备、工艺、关键人员的重大变更；
Experience withmanufacturing of a product (e.g., frequency, volume, number of batches);
产品的生产经验(如频率、产量、批次)；
Test results ofofficial control laboratories.
法定药品检验机构（official control laboratories）的检测结果。
Periodic review
定期回顾
To select,evaluate and interpret trend results of data within the product quality review;
在产品质量回顾中选择、评价和解读(interpret)数据趋势结果；
To interpretmonitoring data (e.g., to support an assessment of the appropriateness ofrevalidation or changes in sampling).
解读监测数据(如，为再验证或取样变更的适宜性评估提供支持)。
Change management/ change control
变更管理/变更控制
To manage changesbased on knowledge and information accumulated in pharmaceutical developmentand during manufacturing;
基于药品研发和生产过程中所积累的知识与信息来管理变更；
To evaluate theimpact of the changes on the availability of the final product;
评价变更对产品可及性的影响；
To evaluate theimpact on product quality of changes to the facility, equipment, material,manufacturing process or technical transfers;
评价对厂房、设备、物料、生产工艺或技术转移的变更对产品质量的影响；
To determine appropriateactions preceding the implementation of a change, e.g., additional testing,(re)qualification, (re)validation or communication with regulators.
确定在变更实施之前要采取的适当措施，如额外的测试、确认或再确认、验证或再验证、或与监管机构的沟通。
Continualimprovement
持续改进
To facilitatecontinual improvement in processes throughout the product lifecycle.
促进整个产品生命周期中过程的持续改进。
II.2 Quality Risk Management as Part of RegulatoryOperations
监管活动中的质量风险管理
Inspection andassessment activities
检查与评估活动
To assist withresource allocation including, for example, inspection planning and frequency,and inspection and assessment intensity (see "Auditing" Section inAnnex II.1);
有助于资源分配，例如检查的计划和频率，以及检查和评估的深度(见附录Ⅱ.1中的“审计”部分)；
To evaluate thesignificance of, for example, quality defects, potential recalls andinspectional findings;评价如质量缺陷、潜在的召回及检查发现项等的重要性；
To determine theappropriateness and type of post-inspection regulatory follow-up;
确定检查后跟踪监管措施的类型和适宜性；
To evaluateinformation submitted by industry including pharmaceutical development information;
评价企业递交的包括药品研发在内的信息；
To evaluate impactof proposed variations or changes;
评价提交的变更带来的影响；
To identify riskswhich should be communicated between inspectors and assessors to facilitatebetter understanding of how risks can be or are controlled (e.g., parametricrelease, Process Analytical Technology (PAT)).
识别检查员和审评员之间需要进行沟通的风险，以更好地理解应如何控制风险及实际风险是如何控制的(例如：参数放行、过程分析技术(PAT))。
II.3 Quality Risk Management as Part ofdevelopment
药品研发中的质量风险管理
To design aquality product and its manufacturing process to consistently deliver theintended performance of the product (see ICH Q8);
设计一个高质量的产品，以及能持续生产出符合其预期质量水平的产品的生产工艺。(参见ICH Q8)
To enhanceknowledge of product performance over a wide range of material attributes(e.g., particle size distribution, moisture content, flow properties),processing options and process parameters;
增加在较宽范围内（wide range）的物料属性（如粒度分布、水分含量、流动性）、工艺可选项及工艺参数方面的产品性能知识；
To assess thecritical attributes of raw materials, solvents, Active PharmaceuticalIngredient (API) starting materials, APIs, excipients, or packaging materials;
评估原材料、溶剂、原料药的起始物料、原料药、辅料或包装材料的关键属性；
To establishappropriate specifications, identify critical process parameters and establishmanufacturing controls (e.g., using information from pharmaceutical developmentstudies regarding the clinical significance of quality attributes and theability to control them during processing);
建立适当的标准，确定关键工艺参数，以及建立生产控制(如利用从药品研发研究中关于质量属性的临床意义，和在生产工艺中对这些质量属性控制能力的信息)；
To decreasevariability of quality attributes:
减少质量属性的差异性（variability）：
reduce product andmaterial defects;
减少产品及物料的缺陷；
reducemanufacturing defects.
减少生产缺陷。
To assess the needfor additional studies (e.g., bioequivalence, stability) relating to scale upand technology transfer;
评估是否需要进行工艺放大和技术转移相关的额外研究(如生物等效性，稳定性)；
To make use of the“design space” concept (see ICH Q8).
使用“设计空间”的概念(参见ICH Q8)。
II.4 Quality Risk Management for Facilities,Equipment and Utilities
厂房设施、设备和公用系统中的质量风险管理
Design of facility/ equipment
厂房设施和设备的设计
To determineappropriate zones when designing buildings and facilities, e.g.,
在设计建筑和厂房时，确定合适的区域划分，例如，
flow of materialand personnel;
人流和物流；
minimizecontamination;
污染最小化；
pest controlmeasures;
虫害控制措施；
prevention ofmix-ups;
防止混淆；
open versus closedequipment;
开放式设备或密闭式设备；
clean rooms versusisolator technologies;
洁净室或隔离器技术；
dedicated orsegregated facilities / equipment.
专用的或区隔（segregated）的厂房设施、设备
To determineappropriate product contact materials for equipment and containers (e.g.,selection of stainless steel grade, gaskets, lubricants);
确定设备和容器与产品接触部位的适当材质(如不锈钢级别、垫圈、润滑剂的选择)；
To determineappropriate utilities (e.g., steam, gases, power source, compressed air,heating, ventilation and air conditioning (HVAC), water);确定适当的公用系统(如蒸汽、气体、电源、压缩空气、水和空调系统)；
To determineappropriate preventive maintenance for associated equipment (e.g., inventory ofnecessary spare parts).
确定相关设备适当的预防性维护(如必要的备件清单)。
Hygiene aspects infacilities
厂房设施的卫生状况
To protect theproduct from environmental hazards, including chemical, microbiological, andphysical hazards (e.g., determining appropriate clothing and gowning, hygieneconcerns);
保护产品免受环境危害源的影响，包括化学、微生物和物理的危害源(如确定适当的工作服和更衣，卫生)；
To protect theenvironment (e.g., personnel, potential for cross-contamination) from hazardsrelated to the product being manufactured.
保护环境免受在产产品的相关危害源（如人员，潜在的交叉污染）的影响。
Qualification of facility/equipment/utilities
厂房设施、设备和公用系统的确认
To determine thescope and extent of qualification of facilities, buildings, and productionequipment and/or laboratory instruments (including proper calibration methods).
确定厂房设施、建筑物、生产设备和实验室仪器确认的范围和程度(包括适当的校准方法)。
Cleaning ofequipment and environmental control
设备清洁及环境控制
To differentiateefforts and decisions based on the intended use (e.g., multi- versussingle-purpose, batch versus continuous production);
根据预期用途(如多用途与单一用途、批次生产与连续生产)区分所需的投入及决策；
To determineacceptable (specified) cleaning validation limits.
确定清洁验证可接受（规定）限度。
Calibration/preventivemaintenance
校准和预防性维护
To set appropriatecalibration and maintenance schedules.
设定适当的校准和维护计划。
Computer systemsand computer controlled equipment
计算机系统及计算机控制的设备
To select thedesign of computer hardware and software (e.g., modular, structured, faulttolerance);
选择计算机硬件和软件的设计(如模块化，结构化，容错系统)；
To determine theextent of validation, e.g.,
确定验证的程度，例如
identification ofcritical performance parameters;
关键性能参数的识别；
selectionof the requirements and design;
需求与设计的选择；
code review;
源代码的审核；
the extent oftesting and test methods;
测试程度和测试方法；
reliability ofelectronic records and signatures.
电子记录及电子签名的可靠性。
II.5 Quality Risk Management as Part of MaterialsManagement
物料管理中的质量风险管理
Assessment andevaluation of suppliers and contract manufacturers
对供应商和受托方进行评估和评价
To provide acomprehensive evaluation of suppliers and contract manufacturers (e.g.,auditing, supplier quality agreements).
对供应商和受托方进行全面的评价(如审计，供应商质量协议)。
Starting material
起始物料
To assessdifferences and possible quality risks associated with variability in startingmaterials (e.g., age, route of synthesis).
评估由起始物料的变化(如年限(age)、合成路线)引发的差异以及可能的质量风险。
Use of materials
物料使用
To determinewhether it is appropriate to use material under quarantine (e.g., for furtherinternal processing);
确定是否可以使用待验物料（如进入后续的内部工序）；
To determineappropriateness of reprocessing, reworking, use of returned goods.
确定返工、重新加工以及使用退货的适宜性。
Storage, logisticsand distribution conditions
储存、物流以及发运条件
To assess theadequacy of arrangements to ensure maintenance of appropriate storage andtransport conditions (e.g., temperature, humidity, container design);
评估用来确保维持适当的储存和运输条件(如温度、湿度和容器设计)的措施是否充分；
To determine theeffect on product quality of discrepancies in storage or transport conditions(e.g., cold chain management) in conjunction with other ICH guidelines;
结合其它ICH指南，确定偏离储存或运输条件(如冷链管理)对产品质量的影响；
To maintaininfrastructure (e.g., capacity to ensure proper shipping conditions, interimstorage, handling of hazardous materials and controlled substances, customsclearance);
维护基础设施(如，确保适当运输条件、临时储存、危险品和管制物料的处理、清关的能力)；
To provideinformation for ensuring the availability of pharmaceuticals (e.g., rankingrisks to the supply chain).
提供确保药品可及性信息(如对供应链风险进行排序)。
II.6 Quality Risk Management as Part of Production
质量风险管理在药物生产中的应用
Validation
验证
To identify thescope and extent of verification, qualification and validation activities(e.g., analytical methods, processes, equipment and cleaning methods;
确定验证和确认活动（例如，分析方法、工艺、设备和清洁方法）的范围和程度;
To determine theextent for follow-up activities (e.g., sampling, monitoring and re-validation);
确定验证后活动（例如，取样、监测和再验证）的程度;
To distinguishbetween critical and non-critical process steps to facilitate design of avalidation study.
分清关键和非关键工艺步骤，以帮助验证研究的设计。
In-processsampling & testing
中控取样&测试
To evaluate thefrequency and extent of in-process control testing (e.g., to justify reducedtesting under conditions of proven control);
评估工艺控制测试的频率和程度（例如，证实在有效控制的条件下减少测试的合理性）;
To evaluate andjustify the use of process analytical technologies (PAT) in conjunction withparametric and real time release.
评估和证明过程分析技术（PAT）应用于参数放行和实时放行的合理性。
Productionplanning
生产计划
To determineappropriate production planning (e.g., dedicated, campaign and concurrentproduction process sequences).
确定适当的生产计划（例如，专用、阶段性和同步的生产工艺顺序）。
II.7 Quality Risk Management as Part of LaboratoryControl and Stability Studies
质量风险管理在实验室控制和稳定性研究中的应用
Out ofspecification results
检验结果超标（OOS）
To identifypotential root causes and corrective actions during the investigation of out ofspecification results.
在OOS结果调查期间确定潜在的根本原因和纠正措施。
Retest period /expiration date
复验期/有效期
To evaluateadequacy of storage and testing of intermediates, excipients and startingmaterials.
评估中间体、辅料和起始物料的储存和测试是否充分。
II.8 Quality Risk Management as Part of Packagingand Labelling
质量风险管理在包装和标签中的应用
Design of packages
包装设计
To design the secondarypackage for the protection of primary packaged product (e.g., to ensure productauthenticity, label legibility).
设计外包装，以保护已完成内包装的产品（例如，确保产品的真实性、标签的可读性）。
Selection ofcontainer closure system
容器密封系统的选择
To determine thecritical parameters of the container closure system.
确定容器密封系统的关键参数。
Label controls
标签控制
To design labelcontrol procedures based on the potential for mix-ups involving differentproduct labels, including different versions of the same label.
根据不同产品标签（包括同一标签的不同版本）混淆的可能性来设计标签控制程序。
II.9 Quality Risk Management as Part of SupplyChain Control
质量风险管理在供应链控制中的应用
With regard toproduct availability risks related to quality/manufacturing issues, lifecycleoversight of the supply chain includes maintaining current knowledge ofquality/manufacturing hazards and prioritizing efforts to manage such risks.Understanding hazards to quality/manufacturing is critical to maintainingsupply predictability. When risks are well understood and minimized, a higherconfidence in product availability can be attained.
关于与质量/制造问题相关的产品可用性风险，供应链的生命周期监督包括保持对质量/制造危害的当前了解，并确定管理这些风险的优先顺序。了解对质量/制造的危害对于保持供应可预测性至关重要。当充分了解风险冰冰将其降至最低时，可以对产品可用性获得更高的信心。
ManufacturingProcess Variation and State of Control
生产工艺变更和控制状态
To decreasevariability in the manufacturing process (e.g., process drift, non-uniformity)and associated capability gaps that can result in unpredictable outputs,adversely impact quality and consequently timeliness, yield and productavailability;
减少生产工艺中的可变性（例如，过程漂移、不一致性）和相关的能力差距，这些差距可能导致不可预测的结果，对质量产生不利影响，从而影响及时性、产量和产品可用性;
To designmonitoring systems that are capable of detecting departures from a state ofcontrol and deficiencies in manufacturing processes, so they can beappropriately investigated to determine root causes and any required riskmitigations.
设计出能够检测控制状态偏离和生产工艺缺陷的监控系统，以便对这些变化进行适当调查，以确定根本原因和任何所需的风险降低措施。
ManufacturingFacilities
生产设施
To ensure thatfacility infrastructure and equipment are suitable and well-designed formanufacturing and packaging;
确保厂房的基础设施和设备对生产和包装而言是适宜且经过良好设计的；
To establishequipment and facility maintenance programmes that assure reliable facility andequipment performance;
建立设备和厂房设施维护程序确保设备和厂房设施可靠；
To ensure that theoperational design of equipment is not vulnerable to human error;
确保设备的操作设计不易导致人员差错；
To obtainefficiency gains (e.g. speed, throughput, supply timeliness, etc.) frominvesting in quality through the utilization of digitalization, automation,isolation technology, and other innovations.
通过数字化、自动化、隔离技术及其它创新技术等质量投入来提高效率（例如速度、产量、供应及时性等）。
Supplier Oversightand Relationships
供应商监督和关系
To enhance reviewand monitoring activities (see Section 2.7 of ICH Q10) when substantialvariability is identified in the quality and safety of supplied materials or inthe services provided.
当发现在所供应物料或所提供服务的质量和安全方面存在重大变化时，应加强审核和监控工作（间ICH Q10第2.7部分）。
To manage externalproduct availability risks relating to quality/manufacturing, (e.g. from rawmaterial suppliers, contracted organizations, service providers, etc.)
管理与质量/生产相关的外部的产品可及性风险（例如原材料供应商、外包组织、服务提供商等）。
