企業(yè)質(zhì)量風(fēng)險管理中英文對照

1、Tabieof【最te新資料亠 WORD文檔§目錄可編輯修改亠I人【Xi1. INTRODUCTION-1引言J1'丿、2. SCOPE范圍3. PRINCIPLES OF QUALITY RISK MANAGEMENT質(zhì)量風(fēng)險管理原理4. GENERAL QUALITY RISK MANAGEMENT PROCESS質(zhì)量風(fēng)險管理基本程序4.1 Resp on sibilities職責(zé)分配4.2 In itiat ing a Quality Risk Man ageme nt Process質(zhì)量風(fēng)險管理的啟動4.3 Risk Assessme nt風(fēng)險評估4.4 Risk C

2、on trol風(fēng)險控制4.5 Risk Commu ni cati on風(fēng)險交流4.6 Risk Review風(fēng)險回顧5. RISK MANAGEMENT METHODOLOGY風(fēng)險管理方法學(xué)6. INTEGRATION OF QUALITY RISK MANAGEMENT INTO INDUSTRY ANDREGULATORY OPERATIONS工業(yè)及監(jiān)管與質(zhì)量風(fēng)險管理的整合7. DEFINITIONS定義8. REFERENCES參考資料Annex I: Risk Man ageme nt Methods and Tools附件I:風(fēng)險管理方法及工具I.1 Basic Risk Mana

3、gement Facilitation MethodsI.1基本風(fēng)險管理簡易方法I.2 Failure Mode Effects An alysis (FMEA)I.2失誤模式影響分析(FMEA)I.3 Failure Mode, Effects and Criticality An alysis (FMECA)I.3失誤模式影響及危險程度分析(FMECA)I.4 Fault Tree An alysis (FTA)I.4故障樹型分析(FTA)I.5 Hazard An alysis and Critical Con trol Points (HACCP)I.5危害分析及關(guān)鍵控制點(HACCP

4、)I.6 Hazard Operability An alysis (HAZOP)I.6危害可操作性分析(HAZOP)I.7 Preliminary Hazard Analysis (PHA)I.7初步危害分析(PHA)I.8 Risk Ranking and FilteringI.8風(fēng)險排序及濾除I.9 Supporting Statistical ToolsI.9輔助統(tǒng)計工具Annex II: Potential Applications for Quality RiskMan ageme nt附件II:質(zhì)量風(fēng)險管理潛在應(yīng)用前景.II.1 Quality Risk Man ageme nt

5、 as Part of I ntegratedII.1綜合質(zhì)量管理中的質(zhì)量風(fēng)險管理Quality Man ageme nt11.2 Quality Risk Management as Part of Regulatory Operati ons11.3 Quality Risk Man ageme nt as Part of developme nt11.4 Quality Risk Management for Facilities,Equipme nt and Utilities11.5 Quality Risk Management as Part of MaterialsMan ag

6、eme nt11.6 Quality Risk Management as Part of Production11.7 Quality Risk Management as Part of LaboratoryControl and Stability Studies11.8 Quality Risk Man ageme nt as Part of Packag ing and Labelli ng1. INTRODUCTIONRisk management principles are effectively utilized in many areas of bus in ess and

7、 gover nment in clud ing finan ce, in sura nee, occupati onal safety, public health, pharmacovigila nee, and by age ncies regulati ng these in dustries. Although there are some examples of the use of quality risk management in the pharmaceutical industry today, they are limited and do not represe nt

8、 the full contributions that risk management has to offer. In addition, the importanee of quality systems has been recognized in the pharmaceutical industry and it is I beco ming evide nt that quality risk man ageme nt is a valuable comp onent of an effective quality system.It is commonly understood

9、 that risk is defined as the comb in ati on of the probability of occurre nee ofharm andthe 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 differe nt pote ntial har

10、ms, place a different probability on each harm occurring andII.2操作優(yōu)化中的應(yīng)用II.3研發(fā)中的應(yīng)用II.4對工具、設(shè)備和設(shè)施的質(zhì)量風(fēng)險管理II.5物料管理中的應(yīng)用II.6生產(chǎn)中的應(yīng)用II.7實驗室控制及穩(wěn)定性研究中的應(yīng)用II.8標(biāo)簽及包裝中的應(yīng)用引言風(fēng)險管理原理在商業(yè)和政府的許多領(lǐng)域都得到了有效 應(yīng)用，如：金融、保險、職業(yè)安全、公共衛(wèi)生、藥物 監(jiān)測及相應(yīng)的監(jiān)管部門。如今質(zhì)量風(fēng)險管理在藥企中 雖有應(yīng)用，但范圍有限，并沒有發(fā)揮岀它的全部效 用。藥企已經(jīng)意識到了質(zhì)量體系的重要性，而質(zhì)量風(fēng) 險管理越來越明顯地成為有效質(zhì)量體系的重要組分。

11、根據(jù)常規(guī)理解，風(fēng)險被定義為傷害發(fā)生的可能性及嚴 重程度。然而，要在不同利益集團之間尋求風(fēng)險管理 應(yīng)用方面的共同認識是相當(dāng)困難的，因為他們認識到 的潛在危害、各危害發(fā)生的可能性及嚴重程度都不 同。藥品相關(guān)的利益集團很多，如病人、醫(yī)療人員和 政府企業(yè)，但是質(zhì)量風(fēng)險管理的首要目的是保護病 人。attribute differe nt severities to each harm .In relati on topharmaceuticals, although there are a variety ofstakeholders, in clud ing patie nts and medical

12、 practiti on ersas well as gover nment and in dustry, the protecti on of thepatient by managing the risk to quality should becon sidered of prime importa nee.The man ufacturi ng and use of a drug (medic in al) product, including its components, necessarily entail some degree of risk. The risk to its

13、 quality is just one component of the藥品生產(chǎn)、使用過程，包括藥品的成分，都會不可避免地引入一定的風(fēng)險。質(zhì)量風(fēng)險只是其中的一部分。|在產(chǎn)品整個生命周期中，確保產(chǎn)品的質(zhì)量，使得藥品_|overall risk. It is important to understand that product質(zhì)量方面的重要性質(zhì)與臨床研究中的一致，做到這些quality should be maintained throughout the product是非常重要的。一個有效的質(zhì)量風(fēng)險管理方法能通過lifecycle such that the attributes tha

14、t are important to the|提供前攝措施，確疋控制研發(fā)和生產(chǎn)中潛在的質(zhì)量冋|quality of the drug (medic in al) product rema in con siste nt|題，來進一步確保藥品質(zhì)量。當(dāng)質(zhì)量問題岀現(xiàn)時，應(yīng)|with those used in the cli ni cal studies. An effective quality用質(zhì)量風(fēng)險管理還能改善決策過程。有效進行質(zhì)量風(fēng)risk management approach can further ensure the high險管理能促使產(chǎn)生更好更正式?jīng)Q策，增強監(jiān)控者對公quali

15、ty of the drug (medic in al) product to the patie nt by司處理潛在風(fēng)險能力的信心，積極影響直接監(jiān)理的程providi ng a proactive means to ide ntify and con trol度和水平。potential quality issues during development andman ufacturi ng. Additi on ally, use of quality riskman ageme nt can improve the decisi on making if a quality's

16、 ability toproblem arises. Effective quality risk man ageme nt can facilitate better and more in formed decisi ons, can provide regulators with greater assura nee of a compa ny deal with potential risks and can beneficially affect the exte nt and level of direct regulatory oversight.The purpose of t

17、his docume nt is to offer a systematic此文件的目的是提供質(zhì)量風(fēng)險管理方面的系統(tǒng)方approach to quality risk management. It serves as a foun dati on or resource docume nt that is in depe ndent of,I法。作為一個基礎(chǔ)性、資源性的文件，它獨立于卻又支持其它ICH質(zhì)量文件，補充藥企和監(jiān)管機構(gòu)內(nèi)已有的yet supports, other ICH Quality docume nts and compleme nts existi ng quality pr

18、actices, requireme nts, sta ndards, and guideli nes with in the pharmaceutical in dustry and regulatory en vir onmen t. It specifically provides guida nee on the pri nciples and some of the tools of quality risk management that can enable more effective and con siste nt risk based decisi ons, both b

19、y regulators and in dustry, regard ing the quality of drug substa nces and drug (medic in al) products across the product lifecycle. It is not inten ded to create any new expectati ons bey ond the curre nt regulatory requireme nts.質(zhì)量措施、要求、標(biāo)準(zhǔn)和指南。特別是它提供了一些 質(zhì)量風(fēng)險管理工具的原理指南，這些工具能促使監(jiān)管 者和企業(yè)考慮整個產(chǎn)品周期中藥用物質(zhì)和藥品的

20、質(zhì) 量，做出更有效、更連續(xù)的基于風(fēng)險的決策，并不想 在現(xiàn)有法規(guī)之外提岀新的期望。It is neither always appropriate nor always necessary to use a formal risk man ageme nt process (us ing recog ni zed tools and/ or internal procedures e.g., sta ndard operati ng procedures). The use of in formal risk man ageme nt processes (us ing empirical to

21、ols and/ or internal procedures) can also be con sidered acceptable.Appropriate use of quality risk management can facilitate but does not obviate in dustry' s obligati on to compregulatory requireme nts and does not replace appropriate commu ni cati ons betwee n in dustry and regulators.應(yīng)用正式的風(fēng)險

22、管理程序并非總是合適的或必要的（用已承認的工具或內(nèi)部程序，如標(biāo)準(zhǔn)操作規(guī)程）。有時也允許使用非正式的風(fēng)險管理程序（用經(jīng)驗工具或內(nèi)部程序）。恰當(dāng)運用風(fēng)險管理能方便但不消除企業(yè)遵守法規(guī) 要求的責(zé)任，也不能取代企業(yè)和監(jiān)管者之間必要的溝 通交流。y with2. SCOPE2.范圍This guideli ne provides prin ciples and examples of tools for quality risk man ageme nt that can be applied to differe nt aspects of pharmaceutical quality. These

23、aspects本指南給岀了質(zhì)量風(fēng)險管理工具的原理和應(yīng)用實例，這些工具可用于藥品質(zhì)量各方面，即藥用物質(zhì)、藥品、生物和生物技術(shù)產(chǎn)品（包括藥品中用到的原料、溶劑、賦形include development, manufacturing, distribution, and the劑、包裝標(biāo)簽材料等） 生命周期中的研發(fā)、生產(chǎn)、銷售、in specti on and submissi on/review processes throughout the檢察、提交和復(fù)審各過程。lifecycle of drug substa nces, drug (medic in al) products,3.質(zhì)量風(fēng)險

24、管理原理biological and biotech no logical products (in cludi ng the use of raw materials, solve nts, excipie nts, packag ing and labeli ng materials in drug (medic in al) products, biological and biotech no logical products).3. PRINCIPLES OF QUALITY RISK質(zhì)量風(fēng)險管理的兩條基本原理是：1. 評估質(zhì)量風(fēng)險應(yīng)基于科學(xué)知識并最終同對病人的保 護聯(lián)系起來。2.

25、投入的努力程度、管理的正式程度及文件管理水平 應(yīng)與風(fēng)險水平相適應(yīng)。MANAGEMENTTwo primary principles of quality risk management are: ? The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patie nt; and4.質(zhì)量風(fēng)險管理基本過程? The level of effort, formality and documentation o

26、f the quality risk man ageme nt process should be comme nsurate with the level of risk.4. GENERAL QUALITY RISK MANAGEMENT質(zhì)量風(fēng)險管理是對藥品質(zhì)量風(fēng)險進行評估，控制，交 流和審查的系統(tǒng)過程，這一過程貫穿藥品整個生命周 期。圖1給岀了這方面的一個模型，其他模型也有應(yīng) 用。具體情況不同，框架中各組分受重視水平會各有 差別，可是一個有效的管理過程會將所有因素納入考 慮，各因素受關(guān)注程度會因風(fēng)險的特異而各有區(qū)別PROCESSQuality risk man ageme nt is a

27、 systematic process for the assessme nt, con trol, commu ni cati on and review of risks to the quality of the drug (medic in al) product across the product lifecycle. A model for quality risk management is outl ined in the diagram (Figure 1). Other models could be used. The emphasis on each comp one

28、nt of the framework might differ from case to case but a robust process will in corporate con siderati on of all the eleme nts at a level of detail that is comme nsurate with the specific risk.Figure 1:典型質(zhì)量風(fēng)險管理過程簡介啟動質(zhì)量風(fēng)險管理風(fēng)險管理工具由于決策行為隨時都可能發(fā)生，上圖就沒有顯示決策 點。這些決策有可能被反饋到上一步以尋求更多信 息，這些信息可用于調(diào)整風(fēng)險模型；也可能用于管理 過

29、程的終止。注解：圖中的“不可接受”項不僅指違 背了法令法規(guī)要求，也表示風(fēng)險管理過程需要重頭再 來。Decisi on no des are not show n in the diagram above because decisions can occur at any point in the process. These decisi ons might be to retur n to the previous step and seek further information, to adjust the risk models or even to term in ate the

30、risk man ageme nt process based upon in formati onthat supports such a decisi on.Note:“ unacceptable in”he flowchart does not only refer to statutory, legislative or regulatory requirements, but also to the need to revisit the risk assessment process.4.1 Resp on sibilities4.1.職責(zé)分配Quality risk manage

31、ment activities are usually, but not質(zhì)量風(fēng)險管理經(jīng)常是但也不總是由交叉學(xué)科團隊執(zhí)always, undertaken by interdisciplinaryteams. When行。除了要有風(fēng)險管理方面的經(jīng)驗人士，團隊還應(yīng)包teams are formed, they should include experts from the括相關(guān)領(lǐng)域的專家（例如：質(zhì)量小組、事業(yè)發(fā)展、工appropriate areas (e.g., quality un it, bus in ess developme nt.程、管理，生產(chǎn)、行銷、法律、統(tǒng)計和臨床方面等。engin

32、 eeri ng, regulatory affairs,producti on operati ons,決策者必須負責(zé)組織協(xié)調(diào)各部門之間的關(guān)系，保障團sales and marketing, legal, statistics and clinical)in隊各項功能的有效發(fā)揮，確保整個管理過程得以合理addition to individuals who are knowledgeable about the展開、不斷完善、反復(fù)審查，保障有足夠的資源供團quality risk man ageme nt process.隊使用。Decisi on makers should? take r

33、esp on sibilityfor coord in at ingquality riskmanagement across various functions and departments oftheir orga ni zati on; and? assure that a quality risk management process is defined,deployed and reviewed and that adequate resources areavailable.4.2 In itiat ing a Quality Risk Man ageme nt Process

34、4.2質(zhì)量風(fēng)險管理的啟動Quality risk man ageme nt should in clude systematic質(zhì)量風(fēng)險管理應(yīng)包括這樣一些系統(tǒng)程序，這些設(shè)計好processes desig ned to coord in ate, facilitate and improve的程序用來協(xié)調(diào)，推動和改善那些風(fēng)險方面基于科學(xué)science-based decision making with respect to risk.認識的決定。一項管理程序的發(fā)起和設(shè)計可能要經(jīng)過Possible steps used to initiate and plan a quality risk如下

35、步驟：man ageme nt process might in clude the follow ing:?定義存在的難題和風(fēng)險問題，包括識別潛在風(fēng)險的相? Define the problem and/or risk question, including關(guān)假設(shè)；pertinent assumptions identifying the potential for risk;?收集風(fēng)險評估相關(guān)的關(guān)于潛在危險、危害或人體健康? Assemble background information and/ or data on the影響的背景信息和數(shù)據(jù)；pote ntial hazard, ha

36、rm or huma n health impact releva nt to?確定領(lǐng)導(dǎo)人和重要資源；the risk assessme nt;?詳細說明決策的時間表，可交付性和適當(dāng)?shù)臉?biāo)準(zhǔn)。? Ide ntify a leader and n ecessary resources;? Specify a timeline, deliverables and appropriate level of decisi on making for the risk man ageme nt process.4.3 Risk Assessme ntRisk assessment consists of

37、the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards (as defined below). Quality risk assessme nts begi n with a well-defi ned problem descripti on or risk question. When the risk in question is well defined, an appropriate risk management

38、tool (see examples in secti on 5) and the types of in formati on n eeded to address the risk question will be more readily identifiable. As an aid to clearly defining the risk(s) for risk assessment purposes, three fun dame ntal questi ons are ofte n helpful:1. What might go wrong?2. What is the lik

39、elihood (probability) it will go wrong?3. What are the con seque nces (severity)?Risk identificationis a systematic use of information toidentify hazards referring to the risk question or problem description. Informationcan include historical data,theoretical an alysis, in formed opinions, and the c

40、on cer ns of stakeholders. Risk identification addresses the “ What might go wrong? ” question, including identifyingthepossible con seque nces. This provides the basis for further steps in the quality risk man ageme nt process.Risk analysis is the estimation of the risk associated with the identifi

41、ed hazards. It is the qualitative or quantitative process of linking the likelihood of occurrenee and4.3風(fēng)險評估風(fēng)險評估：此過程進行危險確認并對接觸這些危險所 帶來的風(fēng)險進行分析評價。它以一個定義明確的難點 描敘或風(fēng)險問題開始，當(dāng)風(fēng)險明確后，選擇合適而有 針對性的管理工具和信息類型將會變得更容易。以下 三個基本問題將有助于給岀風(fēng)險的清晰定義。1. 什么可能會出錯？2. 岀錯的可能性有多大？3. 岀錯的后果和嚴重性有哪些？風(fēng)險鑒定： 參照風(fēng)險問題或難點描敘，系統(tǒng)利用已有 信息去鑒定危險。這些信

42、息包括歷史數(shù)據(jù)、理論分 析、多方面觀點和風(fēng)險承擔(dān)人的意見。風(fēng)險鑒定時提 出“什么會出錯”這一問題，同時還確定可能答案。 這一過程為后續(xù)步驟奠定了基礎(chǔ)。風(fēng)險分析： 估計與已確認危險相聯(lián)系的風(fēng)險，這是對危害發(fā)生的可能性和嚴重程度進行定性和定量分析的過程。風(fēng)險評價中同樣也應(yīng)用到某些管理工具檢測危severity of harms. In some risk management tools, the ability to detect the harm (detectability) also factors in the estimation of risk.害的能力（檢測能力）。Risk eva

43、luation compares the identified and analyzed risk against given risk criteria. Risk evaluations consider the stre ngth of evide nee for all three of the fun dame ntal questi ons.In doing an effective risk assessme nt, the robust ness of the data set is important because it determines the quality of

44、the output. Reveali ng assumpti ons and reas on able sources of un certa inty will enhance con fide nee in this output and/or help identify its limitations. Uncertainty is due to comb in ati on of in complete kno wledge about a process and its expected or unexpected variability. Typical sources of u

45、n certa intyin cludegaps in kno wledge gaps inpharmaceutical scie nee and process un dersta nding, sources of harm (e.g., failure modes of a process, sources of variability), and probability of detecti on of problems.The output of a risk assessment is either a quantitative estimate of risk or a qual

46、itative description of a range of risk. When risk is expressed quantitatively, a numerical probability is used. Alter natively, risk can be expressed using qualitative descriptors, such as“ high ”"low "which should be defined in as much detail as possible. Sometimes a "risk score"

47、; is used to further defi ne descriptors in risk ranking. Inqua ntitativeriskassessments, a risk estimate provides the likelihood of a specific consequenee, given a set of risk-generating風(fēng)險評估：將經(jīng)過分析和鑒定的風(fēng)險同給定標(biāo)準(zhǔn)作比 較，考慮三個基本問題的證據(jù)力。風(fēng)險評估中，數(shù)據(jù) 的有效性決定了評估結(jié)果的質(zhì)量。揭示、設(shè)想、分析 不確定性的來源將有助于增強對結(jié)果的信心、識別結(jié) 果的局限性。對過程了解不充分、過程

48、中可預(yù)見及不 可預(yù)見變動的發(fā)生，都將導(dǎo)致不確定性的發(fā)生。知識 結(jié)構(gòu)的不完整，有限的藥學(xué)發(fā)展水平、不充分的過程 理解、危險來源（不成功的過程模式、變動的來源）及 問題被發(fā)現(xiàn)的可能性都是不確定性的典型來源。評估結(jié)果可以是對風(fēng)險的定量表示，也可以是對分險程度的定性描述。定量表示時可用數(shù)值表示可能性，用 高、中、低來給風(fēng)險排序時，各個詞的適用范圍都 要詳細規(guī)定，有時候還用到風(fēng)險評分來進一步定義。 定量評估能對給定的風(fēng)險衍生環(huán)境中特定結(jié)果發(fā)生的 可能性做岀判斷。因此，定量評估一次只能評判一個 特定結(jié)果。于是一些管理工具用到相對衡量尺度，將 多重水平的嚴重性和可能性結(jié)合起來，以完成對相對 風(fēng)險的整體評估。

49、評分過程的中間步驟有時也用到定 量風(fēng)險估計方法?！癐-刀,medium , orcircumstances. Thus, quantitative risk estimation is useful for one particular con seque nee at a time. Alter natively, some risk management tools use a relative risk measure to combine multiple levels of severity and probability into an overall estimate of re

50、lative risk. The in termediate steps within a scori ng process can sometimes employ quantitative risk estimation.4.4 Risk Con trolRisk 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 f

51、or risk control should be proportional to the significance of the risk. Decision makers might use different processes, includingbenefit-cost analysis, for understanding theoptimal level of risk con trol.Risk con trol might focus on the follow ing questi ons:? Is the risk above an acceptable level? W

52、hat can be done to reduce or elim in ate risks? What is the appropriate bala nce among ben efits, risks and resources? Are new risks introduced as a result of the identified risks being con trolled?Risk reduction focuses on processes for mitigation or avoidance of quality risk when it exceeds a spec

53、ified (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 be4.4風(fēng)險控制風(fēng)險控制包括風(fēng)險抑低和風(fēng)險接受兩方面的決策過程，進行控制的目的是將風(fēng)險降低到可接受水平，投入努力量應(yīng)與風(fēng)險的嚴重程度相襯。決策者應(yīng)用包括 效益-耗費比分析在

54、內(nèi)的不同的程序去理解風(fēng)險控制的 最佳水平。風(fēng)險控制過程中以下問題會受到關(guān)注： 風(fēng)險水平是否高于可接受水平之上？ 怎樣做才能降低乃至消除風(fēng)險？ 如何尋求效益、風(fēng)險和資源之間的合適平衡？ 對已確定風(fēng)險進行控制時是否會引入新的風(fēng)險？風(fēng)險抑低：此過程著力于減輕或避免超過一定水平（可接受水平）的質(zhì)量風(fēng)險，包括為減輕危害嚴重性和發(fā)生 可能性而采取的一系列措施，還包括一些致力于改善 危險及質(zhì)量風(fēng)險可檢測性的程序。風(fēng)險抑低過程可能 會給系統(tǒng)帶入新的風(fēng)險，其他業(yè)已存在的風(fēng)險的嚴重 程度也可能增加。因此，完成風(fēng)險抑低程序后，有必used as part of a risk control strategy. Th

55、e implementation of risk reduction measures can introduce new risks into the system or in crease the sig nifica nee of other exist ing risks. Hence, it might be appropriate to revisit the risk assessme nt to ide ntify and evaluate any possible cha nge in risk after implementing a risk reduction proc

56、ess.要再重復(fù)一下質(zhì)量評估過程，來識別和評價風(fēng)險系統(tǒng) 的可能變化。Risk acceptanee is a decision to accept risk. Risk風(fēng)險接受：就是接受風(fēng)險的決定。它可能為接受殘留accepta nee can be a formal decisi on to accept the residual風(fēng)險的正式?jīng)Q定，也可以是忽略剩余風(fēng)險的消極決risk or it can be a passive decision in which residual risks定。有些類型的風(fēng)險，即使用最好的質(zhì)量風(fēng)險管理手are not specified. For some types of harms, eve n the best段，也不能完全清除。在這種情形下，應(yīng)確認使用了quality risk management practices might not entirely合適的風(fēng)險管理策略，且風(fēng)險已被降至特定水平（可接elim in ate risk. In these circumsta nces, it might be agreed受水平）。這個可接受水平由很多參數(shù)和各例具體情況that an appropriate quality risk management strategy has來確定。been applied and that qu