【正文】 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. The manufacturing and use of a drug (medicinal) product, including its ponents, necessarily entail some degree of risk. The risk to its quality is just one ponent 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 pany’s ability to deal with potential risks and can beneficially affect the extent and level of direct regulatory oversight. 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 plements 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. It is neither always appropriate nor always necessary to use a formal risk management process (using recognized tools and/ or internal procedures ., standard operating procedures). The use of informal risk management processes (using empirical tools and/ or internal procedures) can also be considered acceptable. Appropriate use of quality risk management can facilitate but does not obviateindustry’s obligation to ply with regulatory requirements and does not replace appropriate munications between industry and regulators. 2. SCOPE 范圍 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 提供了 質(zhì)量風(fēng)險(xiǎn)管理 的原理和實(shí)例，可用于制藥質(zhì)量的不同方面。 4. GENERAL QUALITY RISK MANAGEMENT PROCESS 一般質(zhì)量風(fēng)險(xiǎn)管理過程 Quality risk management is a systematic process for the assessment, control, munication 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 ponent 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 mensurate with the specific risk. 質(zhì)量風(fēng)險(xiǎn) 管理是藥品在整個(gè)產(chǎn)品周期內(nèi)質(zhì)量風(fēng)險(xiǎn)的評估、控制、溝通和檢查的一個(gè)系統(tǒng)過程。 Figure 1: Overview of a typical quality risk management process圖 1：典型質(zhì)量風(fēng)險(xiǎn)管理過程概要 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. 決定節(jié)點(diǎn)在上圖沒有說明，因?yàn)闆Q定可發(fā)生在過程的任何一點(diǎn)。 小組形成后，除了在質(zhì)量風(fēng)險(xiǎn)管理方面頗有見識的人外，還應(yīng)包括來自相關(guān)領(lǐng)域（比如質(zhì)量、商務(wù)開發(fā)、工程、法規(guī)事務(wù)、生產(chǎn)操作、市場營銷、立法、統(tǒng)計(jì)和臨床）的專家。 用于啟動(dòng)并計(jì)劃質(zhì)量風(fēng)險(xiǎn)管理過程的步驟可包括以下幾步： ? Define the problem and/or risk question, including pertinent assumptions identifying the potential for risk。 Risk Assessment 風(fēng)險(xiǎn)評估 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 welldefined 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: 風(fēng)險(xiǎn)評估 包括鑒定危險(xiǎn)并對這些危險(xiǎn)產(chǎn)生的相關(guān)風(fēng)險(xiǎn)進(jìn)行分析和評估（定義見下文）。 信息可包括歷史數(shù)據(jù)、理論分析、多方觀點(diǎn)、以及 風(fēng)險(xiǎn)承擔(dān)者 所關(guān)心的問題。 這是定量或定性地將發(fā)生 的 可能性與危害 的 嚴(yán)重性聯(lián)系起來的過程。 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 bination of inplete knowledge about a process and its expected or unexpected variability. Typical sources of uncertainty include gaps in knowledge gaps in pharmaceutic