G04016質(zhì)量風(fēng)險管理規(guī)程-110726.doc

深圳九新藥業(yè)有限公司 Gosun Pharmaceutical Co., Ltd.標(biāo) 題：藥品質(zhì)量風(fēng)險管理規(guī)程Title:Quality Risk Management Procedure版 本： 第一版Version： 01頁 號： Page：014/13編 號Document number：Q/GS G04. 016-11ZG1. 目的 Objective建立質(zhì)量風(fēng)險管理程序，對可能影響到最終產(chǎn)品質(zhì)量的風(fēng)險因素進(jìn)行確定，評估和控制，保證最終的產(chǎn)品質(zhì)量。指導(dǎo)公司規(guī)避質(zhì)量事故或藥害事件的發(fā)生，保護(hù)患者的切身利益。The Quality Risk Management Procedure is established to define, evaluate and control potential risks to product quality, and to help to avoid adverse quality issues or accidents so as to assure patient benefit. 2. 范圍 Scope適用于公司質(zhì)量體系內(nèi)的質(zhì)量風(fēng)險管理。This procedure applies to quality risk management of Gosun quality system. 3. 責(zé)任 Responsibilities3.1所有人員職責(zé)：按本規(guī)程執(zhí)行質(zhì)量風(fēng)險評估，準(zhǔn)備文件。It is the responsibility of all personnel conducting Quality Risk Assessment and preparing the documents to adhere to this procedure.3.2質(zhì)量風(fēng)險管理組長Team leader of quality risk management3.2.1負(fù)責(zé)協(xié)調(diào)跨職能和部門的質(zhì)量風(fēng)險管理。Take responsibility for coordinating quality risk management across various functions and departments of the organization.3.2.2確保質(zhì)量風(fēng)險管理程序按本SOP規(guī)定執(zhí)行，并且有充足的資源可用。Assure that the quality risk management process as defined in this SOP is followed and that adequate resources are available.3.3質(zhì)量受權(quán)人：負(fù)責(zé)批準(zhǔn)質(zhì)量風(fēng)險評估表 及關(guān)閉風(fēng)險管理程序。The Qualified Person: approve and closing of a risk management process. 3.4 QA辦：負(fù)責(zé)審核在產(chǎn)品生命周期內(nèi)對其質(zhì)量風(fēng)險進(jìn)行評估、控制、信息交流和回顧評審的系統(tǒng)化過程。QA Office: review the systematic process of evaluation, control, communication and review of quality risks during the life circle of products. 4. 引用標(biāo)準(zhǔn)及文件 References藥品生產(chǎn)質(zhì)量管理規(guī)范（現(xiàn)行版） (current )EU GMP 指南 Volume 4ICH Q9 5. 內(nèi)容 Contents5.1定義Definition5.1.1可測定性：發(fā)現(xiàn)或測定危險源存在的能力Detectability - the ability to discover or determine the existence, presence, or fact of a hazard.5.1.2危害：對健康的傷害，包括產(chǎn)品質(zhì)量缺陷或可獲得性造成的傷害Harm - damage to health, including the damage that can occur from loss of product quality or availability.5.1.3危險源：潛在的危害來源。Hazard - the potential source of harm.5.1.4質(zhì)量風(fēng)險管理：一套系統(tǒng)的程序，用于藥物產(chǎn)品生命周期中的風(fēng)險評估、控制、信息交流以及回顧。Quality risk management - a systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product life cycle.5.1.5可能性：有害事件發(fā)生的頻率或可能性。Likelihood - frequency or probability of the adverse event occurring.5.1.6嚴(yán)重性：對危險源可能造成的后果的衡量Severity - A measure of the possible consequences of a hazard.5.1.7風(fēng)險評估：對可能造成系統(tǒng)故障的原因進(jìn)行仔細(xì)檢查，以便做出合理可行的決策，減少或者預(yù)防故障的發(fā)生。Risk Assessment - A careful examination of what could cause failure of the system so that decisions can be made about what is reasonably practicable to reduce or prevent malfunctions.5.2質(zhì)量風(fēng)險管理程序的適用范圍包括并不局限于以下情況：This quality risk management procedure applies but not limited to the following issues:5.2.1確定潔凈房間和潔凈空氣設(shè)施的監(jiān)控位置。Defining environmental monitoring positions of clean room and HVAC systems;5.2.2設(shè)定生產(chǎn)的標(biāo)準(zhǔn)和工藝參數(shù)。Establishing limits and parameters of manufacturing process;5.2.3評估變更影響。Evaluating effect of changes;5.2.4確定偏差調(diào)查和糾正措施的程度。Determining levels of deviation investigations and correction actions;5.2.5評估工藝的薄弱和高風(fēng)險區(qū)。Evaluating and defining weakness and high-risk issues of manufacturing process.5.3質(zhì)量風(fēng)險管理流程Quality Risk Management Process 5.4啟動質(zhì)量風(fēng)險管理程序Initiating a Quality Risk Management Process.5.4.1執(zhí)行以下步驟，啟動并計劃質(zhì)量風(fēng)險管理程序。A quality risk management process is planned and initiated as follows: 5.4.1.2確定風(fēng)險項目 Define the risk question確定難題或風(fēng)險問題，包括對相關(guān)潛在風(fēng)險的設(shè)想。質(zhì)量風(fēng)險評估從一個定義明確的難題或風(fēng)險疑問開始。Define the problem and/or risk question, including pertinent assumptions identifying the potential for risk. Quality risk assessments begin with a well-defined problem description or risk question.5.4.1.3組建質(zhì)量風(fēng)險管理小組 Organize a quality risk management team 由難題或風(fēng)險問題部門負(fù)責(zé)人或其指定的人員擔(dān)任組長，風(fēng)險管理小組的成員應(yīng)該至少包括該難題或風(fēng)險問題部門的成員及QA人員。同時根據(jù)需要，也可以邀請其他相關(guān)部門的專業(yè)成員參加。The person in charge of or the person designated by the person in charge of the department which possesses the problem or risk question is designated as the leader of quality risk management team, and personnel engaged in the department which possesses the problem or risk question QA personnel should be involved in the quality risk management team at least. Experts of other relevant department might be involved in the team, where necessary. 5.4.1.4風(fēng)險管理小組組長，搜集潛在危險源、危害或風(fēng)險評估相關(guān)的人員健康影響的背景資料或數(shù)據(jù)，并向風(fēng)險管理小組的成員講解整個項目的情況，幫助風(fēng)險管理小組成員了解整個項目。The leader of quality risk management team assembles background information and/or data on the potential hazard, harm or human health impact relevant to the risk assessment and explains the program to team members to help them get to know this program. 5.4.1.5風(fēng)險管理小組成員依據(jù)自己的專業(yè)，使用5.6中介紹的質(zhì)量風(fēng)險管理方法，找到該項目中可能存在的影響到產(chǎn)品質(zhì)量的危險源，并對這些危險源進(jìn)行分析討論，確認(rèn)各類危險源對最終產(chǎn)品質(zhì)量影響的嚴(yán)重性，風(fēng)險管理小組組長根據(jù)最后的風(fēng)險分析的結(jié)果，起草質(zhì)量風(fēng)險評估表（編號：G04.016- R1）第一部分內(nèi)容，質(zhì)量風(fēng)險評估表第一部分的內(nèi)容應(yīng)包括但不限于：風(fēng)險項目名稱、存在的危險源、風(fēng)險發(fā)生后的危害、目前的控制方式等。According to their expertise, quality risk management team members employ the quality risk management tools listed in article 5.6 to identify and analyze potential risk sources that may affect product quality and define the severity; the team leader prepare the first part of Quality Risk assessment Sheet (No.: G04.016- R1 ) based on the conclusion of risk analysis. The content of Quality Risk assessment Sheet includes but is not limited to name of the risk question, existing hazard resources, possible consequences and current controls, etc. 5.4.1.6明確風(fēng)險評估的計劃開始時間和完成時間 Specify the timeline of risk management process. 5.4.2質(zhì)量風(fēng)險分析報告交相關(guān)部門會審，QP批準(zhǔn)質(zhì)量風(fēng)險評估的啟動。After being finished, the quality analysis report is reviewed by relevant departments and approved by Qualified Person before the quality risk assessment program is initiated. 5.4.3從質(zhì)量管理部文件QA處取得質(zhì)量風(fēng)險評估編號，按以下方式編號：QRA yy-mm-dd，yy為兩位年號，mm為兩位月號，dd為兩位月度流水號。文件QA發(fā)放編號的同時登記質(zhì)量風(fēng)險管理臺帳（編號：G04. 016-R3）。The QA personnel in charge of documentation assigns a number to quality risk assessment in the form of “QRA yy-mm-dd”, where “yy” is the last two figures of the year, “mm” is the two figures indicating the month, and “dd” is the two sequential numbers which are renewed monthly. The assigned number is recorded in Quality Risk Management Log (No.: G04. 016-R3) by the QA personnel in charge of documentation. 5.5執(zhí)行正式風(fēng)險評估 Deploy a risk assessment 5.5.1按以下步驟執(zhí)行風(fēng)險評估 The risk assessment is deployed as follows: 5.5.1.1質(zhì)量風(fēng)險評估啟動后，由風(fēng)險管理小組組長組織小組成員，或邀請其它相關(guān)部門的專業(yè)成員，填寫質(zhì)量風(fēng)險評估表（編號：G04.016- R1）第二部分內(nèi)容執(zhí)行正式風(fēng)險評估，第二部分的內(nèi)容應(yīng)包括但不限于：數(shù)據(jù)評估（總結(jié)數(shù)據(jù)的充分性，有效性及其他相關(guān)方面）、風(fēng)險識別、風(fēng)險分析及評估、擬定采用的控制方式，風(fēng)險控制實施的標(biāo)準(zhǔn)等。After a risk assessment is initiated, members of the quality risk management team and/or experts of relevant departments, organized by the team leader, fill out the second part of Quality Risk assessment Sheet (No.: G04.016- R1 ) with (including but not limited to) data assessment (adequacy, effectiveness and other related aspects of the data), risk identification, risk analysis and evaluation, proposed risk control methods, acceptance criteria of execution of risk control, etc. 5.5.1.1.1由風(fēng)險管理小組組長組織小組成員，或邀請其它相關(guān)部門的專業(yè)成員，收集相關(guān)數(shù)據(jù)（歷史數(shù)據(jù)、理論分析、已知的見解或相關(guān)利益者的關(guān)注點），并總結(jié)數(shù)據(jù)的充分性、有效性及其他相關(guān)方面。填入質(zhì)量風(fēng)險評估表（編號：G04.016- R1）的“數(shù)據(jù)評估”中。Members of the quality risk management team and/or experts of relevant departments, organized by the team leader, assemble relevant data (historical data, theoretical analysis, informed opinions or concerns of stakeholders), summarize adequacy, effectiveness and other relevant aspects and fill out the “Data Evaluation” item of the Quality Risk assessment Sheet (No.: G04.016- R1 ).5.5.1.1.2風(fēng)險管理小組成員依據(jù)自己的專業(yè)，根據(jù)風(fēng)險提問（什么可能出錯？）和問題描述，系統(tǒng)地利用“數(shù)據(jù)評估”中的信息來確定該項目中可能存在的影響到產(chǎn)品質(zhì)量的危險源，并填入質(zhì)量風(fēng)險評估表（編號：G04.016- R1）的“風(fēng)險識別”中。According to their expertise, quality risk management team members use fundamental question “what might go wrong” and information listed in “Data Evaluation” mentioned above to identify hazards referring to the risk question or problem description and fill out the “Risk Identification” item of the Quality Risk assessment Sheet (No.: G04.016- R1 ).5.5.1.1.3風(fēng)險分析及評估： 風(fēng)險管理小組對這些危險源進(jìn)行分析討論，確認(rèn)各類危險源對最終產(chǎn)品質(zhì)量影響的嚴(yán)重性以及風(fēng)險發(fā)生的可能性。如若可能，可應(yīng)用風(fēng)險管理工具分析和評價風(fēng)險。風(fēng)險管理工具的適用性由危險源的特點和可能造成的嚴(yán)重性確定。Risk analysis and evaluation: the risk management team estimate hazard resources, define the severity of harms and likelihood of occurrence. Analyze and evaluate risk using risk management tools if appropriate. The appropriateness of the tool will be justified by the nature and probable severity of the hazard. 風(fēng)險控制的目的是為了減少或降低風(fēng)險使其達(dá)到可接受水平。某種情況下，風(fēng)險是可接受的。當(dāng)風(fēng)險超過可接受水平時，必須采取相關(guān)措施以降低或避免質(zhì)量風(fēng)險。The purpose of risk control is to reduce the risk to an acceptable level. In some instances, it is appropriate to accept the risk. When risk exceeds an acceptable level then measures must be proposed for mitigation or avoidance of quality risk. 風(fēng)險減少一般包括危害的嚴(yán)重性和可能性的降低。Risk reduction will generally include actions taken to mitigate the severity and probability of harm. 提高危害的可測定性的步驟和引起的質(zhì)量風(fēng)險也可作為風(fēng)險控制策略的一部分。Processes that improve the detectability of hazards and quality risks may also be used as part of a risk control strategy.風(fēng)險控制方式與風(fēng)險的嚴(yán)重性相呼應(yīng)。 The ways of the quality risk management process should be commensurate with the level of risk. 評估降低風(fēng)險影響的措施，這些措施可能造成新的風(fēng)險或增加早前風(fēng)險的嚴(yán)重性。 Evaluate the impact of risk reduction measures that may introduce new risk or increase the significance of early risk.5.5.1.2風(fēng)險管理小組組長依據(jù)風(fēng)險控制方式制定風(fēng)險控制方式實施計劃，實施計劃中應(yīng)該包括，但不局限于以下內(nèi)容：風(fēng)險控制方式、控制方式的開始時間、控制方式的完成時間、控制方式的負(fù)責(zé)部門及負(fù)責(zé)人等。According to the risk control measures the leader of risk management team prepare a risk control plan, which includes but is not limited to risk control measures, starting time and closing time of risk control measures, responsible person and responsible department for implementation of risk control measures, etc. 5.5.1.3質(zhì)量風(fēng)險分析報告交相關(guān)部門會審，QP批準(zhǔn)質(zhì)量風(fēng)險分析結(jié)果。Quality risk analysis reports are reviewed by relevant departments and the conclusions of quality risk analysis are approved by the Qualified Person. 5.6質(zhì)量風(fēng)險管理記錄 Documentation of quality risk management QA在質(zhì)量風(fēng)險管理記錄（編號：G04. 016- R2）中記錄所有的質(zhì)量風(fēng)險控制實施情況。Implementation of quality risk controls is recorded in Quality Risk Management Record (No.: G04. 016- R2) by QA.5.7質(zhì)量風(fēng)險分析的方法 Quality risk analysis methodology 在風(fēng)險分析及評估過程中，如若可能，應(yīng)用風(fēng)險管理工具分析和評估風(fēng)險。風(fēng)險評估工具的適用性由危險源的特點和可能造成的嚴(yán)重性確定。Analyze and evaluate risk using risk management tools if appropriate. The appropriateness of the tool will be justified by the nature and probable severity of the hazard.基本風(fēng)險管理工具有： Basic risk management tools include: a) 簡易化工具（流程圖、檢查表、頭腦風(fēng)暴等等）Facilitation devices (flow charts, check sheets, brainstorming, etc)b) 失敗模式效果分析（FMEA）Failure Mode Effects Analysis (FMEA)c) 危害分析及關(guān)鍵控制點（HACCP） d) 魚骨圖分析Fishbone Analysis e) 支持的統(tǒng)計學(xué)工具Supporting statistical tools - 某些質(zhì)量風(fēng)險管理工具檢測危險的能力（可測定性）被認(rèn)為是對風(fēng)險的評估。- In some risk management tools, the ability to detect the harm (detectability) is considered in the estimation of risk.- 風(fēng)險評估的結(jié)果要么是對風(fēng)險的定量評估，要么是對風(fēng)險范圍的定性描述。當(dāng)風(fēng)險被定性描述為“高”“中”“低”時，盡量要對其進(jìn)行詳細(xì)描述。- The output of a risk assessment will either be a quantitative estimate of risk or a qualitative description of a range of risk. When risk is expressed using qualitative descriptors, such as “high”, “medium”, or “l(fā)ow”, these must be defined in as much detail as possible.5.8風(fēng)險評估的關(guān)閉 Closing of risk assessment 5.8.1風(fēng)險控制方式實施結(jié)束后，風(fēng)險管理小組組長根據(jù)風(fēng)險控制實施計劃實施的結(jié)果，填寫質(zhì)量風(fēng)險評估表（編號：G04. 016- R1）第三部分內(nèi)容：風(fēng)險控制執(zhí)行完畢后的風(fēng)險再評估，對控制后的風(fēng)險項目按5.5項重新進(jìn)行風(fēng)險評估，以確定風(fēng)險是否消除或降低風(fēng)險至可接受的程度。At the end of execution of risk control protocol, according to the outputs of risk control, the leader of risk management team fills out the third part of Quality Risk Assessment Sheet (No,: G04. 016- R1), Risk Reassessment, to reassess the risk as specified in article 5.5 and to determine if the risk is eliminated or reduced to an acceptable level. 5.8.2風(fēng)險控制執(zhí)行完畢后的風(fēng)險再評估內(nèi)容應(yīng)包括但不限于以下內(nèi)容：控制方式實施后的風(fēng)險結(jié)果、實施風(fēng)險控制方式前后的風(fēng)險對比、實施結(jié)論等。Risk reassessment includes but is not limited to outputs of risk controls, comparison between the risk before and after execution of risk controls, conclusion, etc. 5.8.3質(zhì)量風(fēng)險評估表（編號：G04. 016- R1）第三部分內(nèi)容交相關(guān)部門會審，如果結(jié)論經(jīng)會審確認(rèn)風(fēng)險已經(jīng)消除或降低至可接受程度的，則接受風(fēng)險，由QP關(guān)閉風(fēng)險管理程序；如果結(jié)論經(jīng)會審確認(rèn)風(fēng)險沒有消除或降低至可接受的程度，拒絕風(fēng)險，按照5.5的程序，重新啟動風(fēng)險管理程序，重新啟動風(fēng)險管理程序仍沿用原來的編號，但需在編號后加R，代表一位流水號。舉例：QRA11-07-01R1，表示編號為QRA11-07-01的風(fēng)險評估重新進(jìn)行了1次評估。Relevant departments review the third part of Quality Risk Assessment Sheet (No,: G04. 016- R1). If the review come to a conclusion that the risk is eliminated or reduced to an acceptable level, the risk will be accepted and the Qualified Person close the risk management process; otherwise, the risk management process shall be initiated again as specified in article 5.5. Adding RX at the end of the original QRA number as the QRA number of quality risk re-assessment process, X represent serial number. For example: QRA11-07-01 R1, representing one re-assessment of the quality risk assessment which numbered QRA11-07-01. 5.8.4質(zhì)量風(fēng)險評估表（編號：G04. 016- R1）第三部分內(nèi)容完成后，作為最終風(fēng)險評估驗收的標(biāo)準(zhǔn)之一，來判斷風(fēng)險評估是否最終完成。The content of the third part of Quality Risk Assessment Sheet (No,: G04. 016- R1) is utilized to justify whether a risk assessment process is finished.5.9檔案存儲 Archival and Storage完成的質(zhì)量風(fēng)險評估表（編號：G04. 016- R1）、質(zhì)量風(fēng)險管理記錄（編號：G04. 016- R2）由質(zhì)量管理部文件QA歸檔。Quality Risk Assessment Sheet (No,: G04. 016- R1) and Quality Risk Management Record(No,: G04. 016- R2) are archived by QA personnel in charge of document