GMP驗證過程介紹

1、Introduction to Process Validation過程驗證簡介1Course Contents 課程內(nèi)容Explain what validation is and why we do it 驗證的定義及進行驗證的原因Review what processes need to be validated 檢查什么樣的過程需要驗證Describe an effective process validation 描述一個有效的過程驗證Describe how to manage process validation 描述如何管理過程驗證Sterilization Validatio

2、n Brief Introduction 滅菌驗證簡介2FIRST SECTION第一部分Definitions of Validation 驗證的定義Significance of a Validation 驗證的意義3What is Validation FDA DefinitionFDA對驗證的定義Established documented evidence which provide a high degree of assurance that a specific process will consistently produce a product meeting its pr

3、edetermined specification and quality attributes. 建立提供高度保證的書面證據(jù)，確保特定過程將持續(xù)生產(chǎn)滿足既定參數(shù)和質(zhì)量屬性的產(chǎn)品。4What is Validation ISO Definition ISO對驗證的定義Confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use are fulfilled.通過測試和提供客觀證據(jù)，確認達到特定預(yù)期用途的特殊要求

4、是否得到滿足。7/28/20225Validation Training5What is Validation Baxters Definition百特公司對驗證的定義“Confirmation by examination and provision of objective evidence that the particular requirements for a specific intended use are consistently fulfilled.” “通過測試和提供客觀證據(jù)，確認達到特定預(yù)期用途的特殊要求是否得到持續(xù)滿足?！?Why do we validate? 為什

5、么我們要進行驗證？1.To control the assessment and implementation of equipment and processes, which might impact product safety, quality or efficacy 為了控制那些可能影響產(chǎn)品安全性, 質(zhì)量或功效的過程的評估和實施.Fulfill regulatory requirement滿足法規(guī)的要求7Validation Learning Curve驗證學(xué)習(xí)曲線Numbers of system errors系統(tǒng)錯誤數(shù)量Begin validation開始驗證Begin Prod

6、uction開始生產(chǎn)Begin Production開始生產(chǎn)End validation結(jié)束驗證Savings 節(jié)省 $Without validation沒有驗證With validation有驗證Time 時間Begin ProcessDevelopment開始過程準備8Benefits of Validation驗證的好處Quality Benefits質(zhì)量方面的好處End User Benefits用戶方面的好處Business Benefits商業(yè)方面的好處9Improve Customer Satisfaction/ Reduce Cost提高客戶滿意度/降低成本Reduce de

7、fects, scrap and rework 減少瑕疵品，廢品和返工Reduce complaints and field corrective actions 減少投訴和區(qū)域糾正措施Reduce development time 縮短準備周期Faster time to market 加快進入市場的步伐10Regulatory Requirements法規(guī)方面的要求Regulatory Agencies require validation: -US FDA via Drug/Device GMPs -EU CE Mark via the MDD/ISO -Japan via the GM

8、Ps -Australia via the TGA 法規(guī)機構(gòu)要求驗證： -美國FDA的藥品及醫(yī)療器械的GMP認證 -歐洲CE標志的MDD及ISO認證 -日本的GMP認證 -澳大利亞的TGA認證111998版中國GMP第七章的第五十七條至第六十條提出了“驗證“的要求：驗證包括哪些方面，什么情況下要驗證，驗證的實施，驗證的歸檔。12SECOND SECTION第二部分What Processes need to be Validated 什么樣的過程需要驗證？13What Process Require Validation 什么樣的過程需要驗證“ All processes that affec

9、t quality must be validated ” “所有影響質(zhì)量的過程都必須驗證。”14Types of Processes that required validation 需要驗證的過程的類型Critical System, e g. Water, air, steam 關(guān)鍵性系統(tǒng)，如水，空氣，蒸汽系統(tǒng)等Product Manufacturing Processes 產(chǎn)品制造過程Product Design Changes 產(chǎn)品設(shè)計變更New or modified equipment 新的或改良的設(shè)備Computer Software 計算機軟件Sterilization 滅菌

10、Analytical Test Methods 分析測試方法Cleaning Methods 清潔方法15THIRD SECTION第三部分Describe an effective Process Validation 描述有效的過程驗證16What are the implication of not effectively validation 無效驗證的含義Extended Development Times 準備時間過長For Unreleased Product 對于未出售的產(chǎn)品 -Elevated scrap 廢品量增加 -Products holds 產(chǎn)品滯留 For Rele

11、ased Products對于已出售的產(chǎn)品 -Litigation 訴訟 -Customer complaints 客戶投訴 -Recalls 召回 -Patient safety concerns 病人安全問題17Validation System Model驗證系統(tǒng)模式Validation- Process Operation -Re-validation驗證 & Monitoring 再驗證 過程操作和監(jiān)控Validation Management驗證管理Validation does not begin or end with the protocol, it is a continu

12、ous improvement process驗證并不會隨驗證方案的開始或結(jié)束而開始或結(jié)束, 它是持續(xù)改進的一個閉合循環(huán)活動18First Step in Validation驗證的第一步Establish a Team 建立一個團隊 -One of the most important things you can do to assure a successful validation is to form a multi-functional team to oversee the validation activities -保證驗證成功的最重要事情之一是，組建一個多功能的團隊來監(jiān)督驗

13、證活動19First Step in Validation驗證的第一步The team members 團隊成員 -Chemist, Microbiologist, Quality Engineer, Project Engineer, Sterility Assurance Engineer, Production Supervisor, Regulation officer, IT -化學(xué)師, 微生物師, 質(zhì)量工程師, 無菌保證工程師, 生產(chǎn)主管, 法規(guī)專員, 信息技術(shù)人員20Validation Following Steps 驗證后續(xù)步驟Define Requirements 說明要求

14、DevelopProtocol 準備驗證方案RunValidation 進行驗證PrepareFinal Report 準備總結(jié)報告Approve & Report 批準并將總結(jié)報告歸檔FMEA / Quality Risk Analysis 失效模式和影響分析(FMEA)/ 質(zhì)量風險分析 High/Mid Risk 高中風險Validation Waiver 驗證豁免Low Risk 低風險21Define Requirements說明要求Define product and process characteristics that could be affected by whats be

15、ing validated. 說明會受驗證內(nèi)容影響的產(chǎn)品和過程的特征 These requirements include:這些要求包括： -Those defined in specifications 質(zhì)量標準說明的內(nèi)容 -Appropriate reference standards, i.e. GMP, ISO, ANSI, USP, MDD, etc. 適當?shù)膮⒖紭藴?，如：GMP, ISO, ANSI, USP, MDD 等 -Additional requirements not covered in specifications and standards質(zhì)量標準和參考標準里未包

16、括的附加要求22Define Requirements說明要求Design inputs - To specify each requirements of product / process, it is including: 設(shè)計輸入 - 說明產(chǎn)品或過程的每一項要求，它包括:- Reliability 可靠性- Characteristics 特征- Physical Requirements 物理要求- Functional Requirements功能要求- Safety Requirements 安全要求- Packaging 包裝要求- Regulatory 法規(guī)要求Design

17、Inputs23Design Inputs設(shè)計輸入3.1 Package Product ReliabilityDESIGN INPUT設(shè)計輸入3.1.1All design inputs must be 99.35% reliable with 95% confidence value unless otherwise stated.所有的設(shè)計輸入必須在95%的可信度上達到99.35% 的可靠性。Ensure all verification testing demonstrates performance to a high level of reliability with a high

18、 degree of confidence保證在高可信度的情況下所有的驗證測試證明結(jié)果具有高水平的可靠性。RATIONALE 基本原理Define Requirements說明要求24Design Inputs設(shè)計輸入3.2 Package Product Characteristics DESIGN INPUT設(shè)計輸入3.2.13.2.2Packaging materials must not degrade from exposure to PVI. 包裝材料必須能在聚維酮碘暴露的環(huán)境下不會降解。The pouch must provide a sanitary environment i

19、n which the cap is contained until the patient is ready to use the cap. 包裝袋必須給碘伏帽提供衛(wèi)生的環(huán)境，直至病人使用。Must maintain a neat appearance for the customer. 使客戶在使用產(chǎn)品時仍保持整潔的外觀。Needed to provide ease of use for the customer.客戶用起來放心，安全。 RATIONALE 基本原理25Failure Modes and Effects Analysis (FMEA): An FMEA is systema

20、tic analysis of the potential failure modes. It includes the identification of possible failure modes, determination of the potential causes and consequences and an analysis of the associated risk. FMEA can be performed on both the product and the process. 失效模式和影響分析(FMEA)：FMEA是對潛在失敗模式的系統(tǒng)分析。它包括可能的失效模

21、式的鑒定，潛在的原因和推理，以及相關(guān)風險的判定。FMEA可適用于產(chǎn)品和過程。FMEA / Quality Risk Analysis 失效模式和影響分析(FMEA) / 質(zhì)量風險分析 26Risk Analysis: Prevention tool used to identify potential failure modes, its causes, and the impact on the system and final user. 風險分析: 識別潛在的失敗模式, 以及它們的起因和對系統(tǒng)及使用者的影響的預(yù)防工具.RequirementsDefinitionPrior to Buil

22、dFix DuringValidationMay Be Much MoreRecalls, Regulatory Action,ComplaintsFMEA / Quality Risk Analysis 失效模式和影響分析(FMEA) / 質(zhì)量風險分析 在之前說明要求在驗證中解決也許更多的產(chǎn)品召回, 法規(guī)措施, 和投訴27FMEA / Quality Risk Analysis 失效模式和影響分析(FMEA) / 質(zhì)量風險分析 O - Occurrence, rating from 1-5 points, rating 5 stands for highest probability O -

23、 代表發(fā)生的可能性, 分1-5個等級, 等級5代表可能性最高S - Severity, rating from 1-5 points, rating 5 stands for most serious S - 代表嚴重程度, 分1-5個等級, 等級5代表程度最嚴重D - Detection, rating from 1-5 points, rating 5 stands for most difficult to detect D - 代表被檢測到的可能性, 分1-5個等級, 等級5代表最難檢測到RPN- Risk Priority Number 風險等級 RPN=O*S*D 風險等級等于以上

24、3個得分的成積Risk Priority Number (RPN) 風險等級28FMEA / Quality Risk Analysis 失效模式和影響分析(FMEA) / 質(zhì)量風險分析 Risk Priority Number (RPN) 風險等級O - OccurrenceRating: 1 = 1/100K 表示發(fā)生的可能性約十萬分之一 2 = 1/10K表示發(fā)生的可能性約萬分之一 3 = 1/1K 表示發(fā)生的可能性約千分之一 4 = 1/100 表示發(fā)生的可能性約百分之一 5 = 1/10表示發(fā)生的可能性約十分之一29S - SeverityRating: 1 = Minor Fail

25、ure (Unlikely to be noticed in the next process)輕微失?。ㄎ幢卦谝院竽懿煊X） 2 = Minor Failure (Downstream annoyance complaints. Causes minor work-arounds in the next process, or additional testing by another department輕微失敗（下游的投訴。引起下一工序的額外工作或其他部門的額外測試） 3 = Moderate failure (Downstream reduction in performance & t

26、hroughput. Causes delays, rework, or capacity reductions in the next process step)中等失?。ㄏ掠蔚纳a(chǎn)能力和表現(xiàn)下降。引起延遲、返工或下一工序的生產(chǎn)能力的下降） 4 = Major Failure (System inoperable or major reduction in performance. Causes loss of product.)主要失?。ㄏ到y(tǒng)不能工作或表現(xiàn)明顯下降。導(dǎo)致產(chǎn)品損失） 5 = Safety and/or regulatory issue. (Causes a non-confo

27、rmance in product efficacy, purity, and/or potency that may not be captured downstream. Causes the process to occur outside approved parameters.)安全和或法規(guī)方面的后果（導(dǎo)致產(chǎn)品的功效，純度，和或潛在的影響不能在下游發(fā)現(xiàn)。導(dǎo)致過程超出了規(guī)定的參數(shù)范圍）FMEA / Quality Risk Analysis 失效模式和影響分析(FMEA) / 質(zhì)量風險分析 Risk Priority Number (RPN) 風險等級30FMEA / Quality

28、Risk Analysis 失效模式和影響分析(FMEA) / 質(zhì)量風險分析 Risk Priority Number (RPN) 風險等級D - DetectionRating: 1 =1/MCompletely mistake proof. Current controls ensure failure prevention / detection prior to passing on to the next step)檢測不到的可能性為百萬分之一，完全能防止錯誤。目前的控制手段能保證防止或發(fā)現(xiàn)失敗進入下一步。2 =1/10KFailure obvious. (Pre-run or in

29、 process quality checks look for possibility of the failure mode)檢測不到的可能性為萬分之一，失敗是顯而易見的。（試運轉(zhuǎn)或過程檢查能發(fā)現(xiàn)這一失?。? =1/1KFailure likely to be detected. (Quality check dont look specifically for this failure mode, but may likely catch them.)檢測不到的可能性為千分之一，失敗有可能被發(fā)現(xiàn)。（質(zhì)量控制的檢查并不是特定用來發(fā)現(xiàn)這一失敗，但有可能發(fā)現(xiàn)到它） 4 =1/100Failur

30、e not obvious. (Quality checks are statically based, or not performed for every run.)檢測不到的可能性為百分之一，失敗不明顯。（質(zhì)量檢查是靜態(tài)進行的，或并不是每次運作時都有質(zhì)量檢查） 5 =1/10No detection plan, chance of missing failure. (No Quality checks in place)檢測不到的可能性為十分之一，沒有探測方案，極有可能放過這一失敗。31FMEA / Quality Risk Analysis 失效模式和影響分析(FMEA) / 質(zhì)量風險

31、分析 Risk level:風險水平: - Low Risk RPN 1.33 for key process.百特公司要求關(guān)鍵過程的Cpk要大于1.33Operational Qualification 運行確認OQ Items 運行確認考慮因素52Operational Qualification 運行確認OQ Items 運行確認考慮因素LSLUSLAn Unstable Process 不穩(wěn)定的過程Grand standard deviation and average are both quite different from that of sub-group.總體的標準偏差及平均

32、值與小組的標準偏差及平均值有較大差異.53Operational Qualification 運行確認OQ Items 運行確認考慮因素A Stable but not Capable Process 穩(wěn)定但沒有能力的過程USLLSLGrand standard deviation and average are both almost the same as that of sub-group. OOL sometimes.總體的標準偏差及平均值與小組的標準偏差及平均值幾乎一致. 有時會超標.54Operational Qualification 運行確認OQ Items 運行確認考慮因素L

33、SLUSLA Stable & Capable Process 穩(wěn)定的和有能力的過程Grand standard deviation and average are both almost the same as that of sub-group. Far away from the limit all the time.總體的標準偏差及平均值與小組的標準偏差及平均值幾乎一致. 而且總是離限度很遠.55The calculation of Cpk:Cpk 的計算：Determine specification limit - USL & LSL 確定規(guī)范限度Calculate average

34、 (X) and standard deviation ( )計算平均值和標準偏差Calculate Cpk計算Cpk Formula is:計算公式：Cpk = (USL X)/3 or (X - LSL)/3 (the min. result is Cpk)Cpk = （上限平均值）個標準偏差或（平均值下限） 個標準偏差取最小的結(jié)果作為Cpk。Operational Qualification 運行確認OQ Items 運行確認考慮因素56There are many tools for helping to achieve stable and capable processes: 有許

35、多工具用于優(yōu)化參數(shù)達到穩(wěn)定和有能力的過程 Control Charts 控制圖 Multi-variant Charts多變量圖 Analysis of Mean均值分析 Component S Studies成分交換研究 Scatter Diagrams離散圖 Response Surface Studies表面響應(yīng)研究 Taguchi Methods田口方法 Variation Transmission Analysis變異轉(zhuǎn)移分析Operational Qualification 運行確認OQ Items 運行確認考慮因素57Performance Qualification-PQ 性能

36、確認“Documented evidence that the process, under all anticipated conditions, consistently produces a product which meets all predetermined requirements.” “過程在所有預(yù)期條件下，持續(xù)生產(chǎn)符合所有既定要求的產(chǎn)品的書面證據(jù)?！盜n this phase, the key objective is to demonstrate the process will consistently produce acceptable product under

37、normal operating conditions. 在本階段，關(guān)鍵目標是演示將在正常操作條件下持續(xù)生產(chǎn)合格產(chǎn)品的過程。58Performance Qualification 性能確認PQ Items 性能確認考慮因素Produce product using process parameters and procedures established in OQ. 使用在運行確認里建立的過程參數(shù)和程序來生產(chǎn)產(chǎn)品Reconfirm acceptability of the products, (assure process capability) 重新確認產(chǎn)品的可接受性（保證過程能力）Dem

38、onstrate Process Repeatability (assure process stability, such as 3 trials) 演示過程的重復(fù)性（保證過程的穩(wěn)定性，如三次試驗）Product release requirements (generally to be released only after final report approval, unless the product quality can be qualified under certain specific procedure, e.g.100% inspection)產(chǎn)品放行的要求 (通常只有

39、在總結(jié)報告批準后才放行, 除非產(chǎn)品的質(zhì)量在某些特定的程序下得到保證, 如有效的100%檢查)59Protocol Phases 方案的各個階段For all three phases IQ, OQ and PQ based on the product / process requirements: 對于基于產(chǎn)品/過程要求的安裝確認，運行確認和性能確認： -Determine what to verify / measure 確定檢驗/測量內(nèi)容 -Determine how to verify / measure 確定檢驗/測量方式 -Determine how many to verify

40、/ measure, i.e. Statistical significance 確定檢驗/測量數(shù)量，如統(tǒng)計顯著性 -Determine Acceptance / Rejection Criteria 確定接受/拒絕標準 -Determine required documentation 確定要求的文件60Determine What to verify / measure 確定檢驗/測量內(nèi)容For a carton using alternative texture, strength must be measured. 對于選用替代紙質(zhì)的紙箱，必須測量其抗壓強度For modified s

41、olution bag, leak test must be conducted. 對于改良的溶液袋，必須進行泄漏測試For Sub-Assy design change, drain time must be evaluated to be meet requirement or not.對于附件設(shè)計的變更，必須評估排液時間是否還是符合要求61Determine How to Verify / Measure確定檢驗/測量方式Utilize standard test methods such as ASTM, ANSI, ISO, USP, etc. When ever possible

42、盡可能利用標準測試法，如ASTM，ANSI，ISO，USP等Test methods should replicate actual use conditions 測試方法必須再現(xiàn)實際使用條件Assure test equipment is calibrated 保證測試設(shè)備經(jīng)校正Assure test method is validated 保證測試方法經(jīng)驗證62Utilize Statistically Valid Techniques 利用有效的統(tǒng)計技術(shù) -Sampling Plan for validation 驗證取樣計劃 Utilize WinSSD software 1.5 ve

43、rsion to determine the sample size during OQ/PQ based on the classification of defect and confidence (95% for OQ and 90% for PQ). 在運行和性能確認階段基于缺陷的分類和所要求的可信度(對于OQ選用95%,對于PQ選用90% ), 應(yīng)用WinSSD軟件來確定樣品量.Determine How Many to Verify / Measure確定檢驗/測量數(shù)量63Determine Confidence 確定可信度輸入缺陷百分率(假設(shè)等于0.65%) (它必須小于缺陷分類

44、所述的AQL值)64Sample size 樣品量可接受缺陷數(shù)65A sample size of 459 with 0 observed defectives allows one to state with 95% confidence that the percent defective is no more than 0.65%.在459個樣品中沒有缺陷被發(fā)現(xiàn)表明該驗證確認的過程所產(chǎn)生的缺陷率低于0.65%的可信度為95%.66Define Acceptance/Rejection Criteria說明接受/拒絕標準Address all product and process req

45、uirements 陳述所有產(chǎn)品和過程要求Establish specific criteria for each requirement, upper and lower limits 為每個要求建立特別標準，高限度和低限度 -Based on product specifications 以產(chǎn)品質(zhì)量標準為基礎(chǔ) -Based on established standards 以已建立標準為基礎(chǔ) -Assure limits will result in a robust process. i.e. Cpk 確保限度在滿足要求的前提下能使過程順利進行，如Cpk67Define Acceptan

46、ce / Rejection Criteria說明接受/拒絕標準Acceptance Criteria 接受標準What to Measure測量內(nèi)容How to Measure測量方法HowMany數(shù)量AcceptanceCriteria接受標準Drain Time Timer n=50 X + 3 SD within 10 mins排液時間 計時器 平均值加 3個標準偏差在 10 分鐘內(nèi) (Variable) Visual Defects Visual n=298 None allowed (AQL=1.0%) 可見缺陷 目測 不允許有Leak Test Squeeze Tester n=

47、4607 No leak allowed(AQL=0.065%)泄漏測試 擠壓機 不允許有泄漏 (Attribute) 68Summarize of the Validation Process驗證過程小結(jié)Steps ( before running ) 步驟（運行前）1. Form a Multifunctional Team 組織一個多功能團隊2. Define Requirements, for Product and Process 說明產(chǎn)品和過程的要求3.Risk Assessment 風險分析4. Prepare Validation Process 準備驗證過程 -IQ, OQ

48、and PQ 安裝、操作和性能確認5. Define What, How, How Many to do, Acceptance Criteria and required documentation for each Phase 說明每個階段應(yīng)有的檢測內(nèi)容、方式和數(shù)量，接受標準及要求的文件69Run Validation 進行驗證The people executing the validation should be trained on: 執(zhí)行驗證的人員應(yīng)接受以下的培訓(xùn):GMPGMPGDP (Good Documentation Practices) 良好的文件規(guī)范Protocol 驗證

49、方案Equipment Safety設(shè)備安全Operation 操作Measurement 測量70Run Validation 進行驗證Be sure to 確保以下內(nèi)容Review the validation with those who will perform the testing 與進行測試的人員審閱驗證2 Retain all defects for root cause analysis 保留所有缺陷樣本以便作根本原因分析3.Document any unusual situation 用文件記錄任何異常情況4.Review all documentation for cla

50、rity & completeness 審閱所有文件的清晰性和完整性71Run Validation 進行驗證Be sure to 確保以下內(nèi)容All materials/samples used/made in OQ should be considered to be experimental materials. 所有用于OQ的物料或OQ造的樣品應(yīng)考慮為只作實驗用.- Storage:儲存:Experimental material must be stored in a quarantine area. 實驗用物料必須儲存在隔離區(qū)域. - Labeling:標識: A.Describe

51、 materials to be used in the validation document.描述物料用于哪個驗證B.Label experimental materials with “Experimental goods for test & evaluation only” and “ Not for Human Use” labels.用“僅作測試和評估用的實驗物品”和“不能使用”的標簽標識實驗用物料72Be sure to 確保以下內(nèi)容All materials/samples used/made in OQ should be considered to be experime

52、ntal materials. 所有用于OQ的物料或OQ造的樣品應(yīng)考慮為只作實驗用.- Testing control:測試控制:A.Tests are performed in specific and controlled areas like quality laboratories, quarantined areas. 測試應(yīng)在特定和受控的區(qū)域進行, 如實驗室, 隔離區(qū)等.B.Perform a line clearance inspection of an area after OQ testing to assure that no experimental materials/

53、OQ samples remain.在OQ測試完成后進行在線清場以保證沒有實驗用的物料/樣品遺留在場.Run Validation 進行驗證73Prepare Final Report 準備總結(jié)報告Contents 內(nèi)容Executive summary執(zhí)行情況Data analysis數(shù)據(jù)分析Final report needs to address each acceptance criteria 總結(jié)報告需要陳述每條接受標準State conclusion 陳述結(jié)論Original Data 原始資料Other referenced documents, I.e. specificati

54、on, drawings, forms, etc. 其他參考文件，如質(zhì)量標準，圖紙，表格等Final review and approval 最終審核和批準74 Report 將總結(jié)報告歸檔Retrievable 可檢索Protected from damage 避免受損75At a minimum, once every five years ensure the validation status of each appropriate process (there is another specific period for sterilization validation) is fo

55、rmally validated and documented. The five-year cycle begins after the initial validation of a process, a formal revalidation of the entire process or a formal verification of the validation status.至少每五年確保每一適當?shù)倪^程(滅菌驗證另有規(guī)定)都已被正式驗證，并有文件記錄。五年周期從初始的過程驗證、正式的整個過程的再驗證或者正式的驗證狀態(tài)確認后開始。 Revalidation 再驗證 76Reval

56、idation is required for: 以下情形要求再驗證Changes in the process 過程變更Changes in Quality Indicator Trends 質(zhì)量指標趨勢的變化Changes in the product or customer usage 產(chǎn)品或客戶用途變更Time, when it could have an impact 時間，如果它可能有影響Product Transfers (A process is transferred from one plant to another) 產(chǎn)品轉(zhuǎn)換（過程由一家工廠轉(zhuǎn)到另一家工廠）Revalid

57、ation再驗證77Fourth Section第四部分Describe how to Manage Process Validation 描述如何管理過程驗證78 Validation ManagementNeed Procedures that Address:驗證管理需要程序說明：Validation system 驗證系統(tǒng)Protocol format & Master protocols 驗證方案格式和主驗證方案Final Report Contents and Organization. 總結(jié)報告的內(nèi)容和組織Final Report review and approval 總結(jié)報告

58、的審核和批準Filing/Tracking system for Final Report 總結(jié)報告的歸檔/跟蹤系統(tǒng)SOP-QM-5579Validation System Procedure驗證系統(tǒng)程序Define what processes require validation 說明什么樣的過程需要驗證Define require activities 說明要求的活動Define responsibilities and approvals 說明職責和批準人員Scope and thoroughness of validation should be commensurate with

59、risk and complexity of the process. 驗證的范圍和程度應(yīng)與過程的風險和復(fù)雜性相稱。SOP-QM-5580Protocol Format Procedure驗證方案格式程序Check List檢查清單Protocol Approve Cover Sheet驗證方案審批封面Protocol Format 驗證方案格式Final Report Cover Sheet總結(jié)報告審批封面81Master Protocol Procedure主驗證方案程序Used when process validation requires multiple protocols to

60、accomplish 用于過程驗證需要多種驗證方案來完成的情況Master Protocol is used to break large validation efforts involving multiple processes into manageable sub-units 主驗證方案用于將包含多種過程的大型驗證劃分為易管理的小單元Master Protocol links in each individual piece and validates the entire process together 主驗證方案連接每個獨立部分，驗證整個過程82Final Report Con