【正文】 l 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.質(zhì)量風(fēng)險管理是一個過程，當將其整合到質(zhì)量體系中時(見附錄 II)可以支持基于科學(xué)和實踐的決策。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 bination (., Probabilistic Risk Assessment). Combined use provides flexibility that can facilitate the application of quality risk management principles.在原料藥和藥物(醫(yī)療)產(chǎn)品質(zhì)量的特定領(lǐng)域運用這些工具可能是恰當?shù)摹?危害分析關(guān)鍵控制點(HACCP)；? Hazard Operability Analysis (HAZOP)?；撅L(fēng)險管理簡易方法(流程圖，核對單等)；? Failure Mode Effects Analysis (FMEA)。Traditionally, risks to quality have been assessed and managed in a variety of informal ways (empirical and/ or internal procedures) based on, for example, pilation of observations, trends and other information. Such approaches continue to provide useful information that might support topics such as handling of plaints, quality defects, deviations and allocation of resources.傳統(tǒng)上，對于質(zhì)量的風(fēng)險的評估和管理是基于多種非正式的方式(經(jīng)驗的，和/或，內(nèi)部程序)，例如，現(xiàn)象匯總、趨勢和其它資料。評審頻率應(yīng)該取決于風(fēng)險水平。 Risk Review 風(fēng)險評審Risk management should be an ongoing part of the quality management process. A mechanism to review or monitor events should be implemented. 質(zhì)量風(fēng)險管理應(yīng)當是質(zhì)量管理過程中的一個進行部分。溝通有可能包括這些相關(guān)方，例如，藥政與業(yè)界、業(yè)界與患者、在一個公司、業(yè)界或藥政當局內(nèi)部等。 Risk Communication風(fēng)險溝通Risk munication: is the sharing of information about risk and risk management between the decision makers and others. Parties can municate 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 municated and documented (see Fig. 1: solid arrows). Communications might include those among interested parties。風(fēng)險接受可以是一個接受剩余風(fēng)險的正式?jīng)Q定或者是當剩余風(fēng)險不具體時的被動接受。改善危險因素和質(zhì)量風(fēng)險可檢測性的過程也可能作為一個風(fēng)險控制策略中的一個部分。用于風(fēng)險控制所作工作量應(yīng)該與風(fēng)險的顯著性相稱。另外，一些風(fēng)險管理工具采用了相對的風(fēng)險度量將多種級別的嚴重性和概率合并到一個完整的相對風(fēng)險估計中。另外，風(fēng)險還可以運用如“高”、“中”或“低”等定性描述詞來表達，對其應(yīng)該盡可能詳細地確定。不確定性是由于關(guān)于過程不完整的知識以及其期望的或非期望的變異性綜合造成。Risk evaluation: pares the identified and analyzed risk against given risk criteria. Risk evaluations consider the strength of evidence for all three of the fundamental questions.風(fēng)險評價：其是比較已經(jīng)辨識和分析的風(fēng)險與給定的風(fēng)險標準進行比較。這為進一步的質(zhì)量風(fēng)險管理過程奠定了基礎(chǔ)。當被討論的風(fēng)險被明確定義后，則將會很容易確定適當?shù)娘L(fēng)險管理工具(見第 5 節(jié)中的例子)和需要用于風(fēng)險問題說明的資料類型。收集與風(fēng)險評估相關(guān)的潛在危險、傷害或影響人體健康的背景信息和資料和/或數(shù)據(jù)；? Identify a leader and necessary resources。 and負責在其組織內(nèi)各職能部門間協(xié)調(diào)質(zhì)量風(fēng)險管理；以及，? assure that a quality risk management process is defined, deployed and reviewed and that adequate resources are available.確保明確，開展與評審了質(zhì)量風(fēng)險管理過程，并有適當?shù)馁Y源。（注：在流程圖中的“不接受”不僅僅是依據(jù)法定、立法或藥政要求，同樣也需要返回風(fēng)險評估過程。也可以使用其他模式。3. PRINCIPLES OF QUALITY RISK MANAGEMENT 質(zhì)量風(fēng)險管理的原則Two primary principles of quality risk management are:質(zhì)量風(fēng)險管理的兩個基本原則為：? The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient。采用非正式的風(fēng)險管理過程(使用經(jīng)驗的工具，和/或內(nèi)部程序)也是可以考慮接受。其作為一個基礎(chǔ)的或資源性的文件，其獨立并支撐其它的ICH 質(zhì)量文件，并對現(xiàn)有的質(zhì)量實踐、要求、標準以及制藥行業(yè)指南與藥政環(huán)境進行補充。通過前瞻意義上辨識與控制在研發(fā)與制造中的潛在質(zhì)量問題，一個有效的質(zhì)量風(fēng)險管理方法能進一步給患者提供高質(zhì)量藥物(醫(yī)療)產(chǎn)品質(zhì)量的保證。對于藥品來說，盡管有多種的風(fēng)險涉眾，包括患者、醫(yī)療從業(yè)人員，以及政府和業(yè)界，運用質(zhì)量風(fēng)險管理都應(yīng)該以保護病人為基本出發(fā)點。如今，盡管在制藥行業(yè)也有一些運用質(zhì)量風(fēng)險管理的例子，但其非常有限，且沒有體現(xiàn)出風(fēng)險管理能提供的全部貢獻。INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE人用藥注冊技術(shù)要求國際協(xié)調(diào)會議ICH Harmonised Tripartite Guideline人用藥注冊技術(shù)要求國際協(xié)調(diào)會議三方協(xié)調(diào)后的指南Quality Risk Management質(zhì)量風(fēng)險管理Current Step 4 version現(xiàn)行第四步版本dated 9 November 20052005 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 remended for adoption to the regulatory bodies of the European Union, Japan and USA.本指南由人用藥注冊技術(shù)要求國際協(xié)調(diào)會議專家工作組根據(jù)人用藥注冊技術(shù)要求國際協(xié)調(diào)會議程序開發(fā)并提交各方的藥政部門咨詢。TABLE OF CONTENTS目錄1. INTRODUCTION 簡介................................................................................12. SCOPE 范圍............................................................................23. PRINCIPLES OF QUALITY RISK MANAGEMENT 質(zhì)量風(fēng)險管理的原則............24. GENERAL QUALITY RISK MANAGEMENT PROCESS 常規(guī)質(zhì)量風(fēng)險管理程序.....2 Responsibilities 職責.....................................................................................4 Initiating a Quality Risk Management Process 啟動質(zhì)量風(fēng)險管理過程.......4 Risk Assessment 風(fēng)險評估...................................................................4 Risk Control風(fēng)險控制....................................................................5 Risk Communication風(fēng)險溝通.....................................................................6 Risk Review 風(fēng)險評審..................................................................65. RISK MANAGEMENT METHODOLOGY 風(fēng)險管理方法學(xué) ...................................76. INTEGRATION OF QUALITY RISK MANAGEMENT INTO INDUSTRY AND REGULATORY OPERATIONS質(zhì)量風(fēng)險管理與業(yè)界及藥政運行整合..................................................87. DEFINITIONS 定義.........................................................................98. REFERENCES 參考文獻.................................................................11Annex 附錄 I: Risk Management Methods and Tools風(fēng)險管理方法與工具... 12 Basic Risk Management Facilitation Methods基本風(fēng)險管理簡易方法 ....... 12 Failure Mode Effects Analysis故障模式效應(yīng)分析(FMEA)..........................12 Failure Mode, Effects and Criticality Analysis 故障模式影響與嚴重性分析(FMECA)....................................................13 Fault Tree Analysis 故障樹分析(FTA)........................................13 Hazard Analysis and Critical Control Points危害分析關(guān)鍵控制點(HACCP)....................................................................14 Hazard Operability Analysis 危害及可操作性分析(HAZOP)..................14 Preliminary Hazard Analysis 預(yù)先危險分析(PHA)...................................15 Risk Ranking and Filtering風(fēng)險排序及過濾 ........................15 Supp