和制藥工程工程全過程相整合調(diào)試和確認效勞

1、和制藥工程工程全過程相整合調(diào)試和確認效勞Agenda議程Introduction 導(dǎo)言Definition and Contents Of I-C&Q Service I-C&Q服務(wù)的定義與內(nèi)容Services Provider and Stakeholders 服務(wù)提供商及相關(guān)方Necessity必要性Implementation 實施References and Acknowledgements 參考文獻與致謝2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 導(dǎo)言Concepts 概念Good Engineering Practice良好工程規(guī)范E

2、stablished engineering methods and standards that are applied throughout the project lifecycle to deliver appropriated cost-effective solution.在項目周期中全程采用已建立的工程方法和標準，以交付合理的、經(jīng)濟有效的解決方案。Commissioning調(diào)試A well planned, documented and managed engineering approach to the start-up and turnover of facilities,

3、 systems, and equipment to the End-User that results in a safe and function environment that meets established design requirements and stakeholder expectations.采用一套良好計劃的、有文件記錄并受管理的工程方法，對工程設(shè)施、系統(tǒng)和設(shè)備進行試車并交付最終用戶，以建立符合既定設(shè)計要求及股東期望的安全、功能良好的環(huán)境。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 導(dǎo)言Concepts (cont.)

4、概念（續(xù)）DQ設(shè)計確認The documented verification that engineering design of a facility, utility or equipment that can affect product quality adhere to approved User Requirement and design specifications. 對可能影響產(chǎn)品質(zhì)量的設(shè)施、公用工程和設(shè)備的工程設(shè)計進行有文件記錄的查證，確認與被批準的用戶需求和設(shè)計描述一致。IQ安裝確認 The documented verification that all aspects

5、 of a facility, utility or equipment that can affect product quality adhere to approved specifications and are correctly installed. 對設(shè)施、公用工程和設(shè)備所有可能影響產(chǎn)品質(zhì)量的方面進行有文件記錄的查證，確認與被批準的描述一致并已得到正確的安裝。 2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 導(dǎo)言Concepts (cont.)概念（續(xù)）OQ操作確認The documented verification that all

6、 aspects of a facility, utility, or equipment that can affect product quality operate as intended throughout all anticipated ranges. 對設(shè)施、公用工程和設(shè)備所有可能影響產(chǎn)品質(zhì)量的方面進行有文件記錄的查證，確認它們在預(yù)期的操作極限內(nèi)運行正確。PQ性能確認The documented verification that all aspects of facility, utility, or equipment that can affect product qual

7、ity perform as intended meeting predetermined acceptance criteria. 對設(shè)施、公用工程和設(shè)備所有可能影響產(chǎn)品質(zhì)量的方面進行有文件記錄的查證，確認其性能符合預(yù)先確定的驗收標準。 2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 導(dǎo)言Concepts (cont.)概念（續(xù)）PV工藝驗證The process of establishing documented evidence which provides a high degree of assurance that a specific

8、 process will consistently produce a product meeting its pre-determined specifications and quality attributes. 建立文件證據(jù)，高度保證在特定生產(chǎn)工藝條件下，可均一地生產(chǎn)符合預(yù)定標準和質(zhì)量屬性的產(chǎn)品的過程。More concepts 更多的概念Risk Based Commensurate with risk 基于風險與風險相適應(yīng)Science Based CQA, CPPs 基于科學(xué)關(guān)鍵質(zhì)量屬性、關(guān)鍵工藝參數(shù)Quality by Design Verify throughout 質(zhì)量源

9、于設(shè)計全過程的驗證Subject Matter Expert Defined Role 學(xué)科問題專家角色定義2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 導(dǎo)言Current Issues Relative to C&Q in Chinese Pharmaceutical Industry 當前中國醫(yī)藥工業(yè)中調(diào)試與確認的相關(guān)問題Limited resource and focus on DQ and QBD is not well acknowledged. 投入資源有限，對設(shè)計確認、質(zhì)量源于設(shè)計等的重點未充分認識。Very rare profess

10、ional C&Q consultants aligned with international standard and practice. 專業(yè)的、與國際標準、規(guī)范接軌的調(diào)試與確認咨詢服務(wù)提供商非常罕見。Lack of local presence of international C&Q consulting expertise and the corresponding local professional engineer supportive team. 國際知名調(diào)試與確認專家罕有常駐中國本地，同時缺乏與其配套的本地專業(yè)工程師支持團隊。Importance of establish

11、ing a real QMS based on good C&Q practices is not well acknowledged by endorser top management. 以良好的調(diào)試與確認實踐為基礎(chǔ)建立一個真正的質(zhì)量管理體系的重要性并未被企業(yè)高層管理人員充分認識。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 導(dǎo)言Current Issues Relative to C&Q in Chinese Pharmaceutical Industry （cont.） 當前中國醫(yī)藥工業(yè)中調(diào)試與確認的相關(guān)問題 （續(xù)）Seldom corre

12、ct applications of risk assessment approach and over-interpreting of GMP regulations without understanding their rationales led to overinvestment of the project. 風險分析方法罕有正確應(yīng)用，未能從基本原理上進行理解，若干GMP法規(guī)被過度解讀導(dǎo)致項目過度投資。Seldom systematic planning at the very beginning, most are crash jobs in the final phase of

13、 the project. 鮮有在項目開始即進行系統(tǒng)性的策劃，大部分在項目后期進行突擊。Frequent change orders due to issues exposed in the final C&Q phase led to significant cost of remedy and delay. 因最終調(diào)試與確認階段暴露的問題而產(chǎn)生的變更導(dǎo)致可觀的索賠及工期延誤。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 導(dǎo)言Current Issues Relative to C&Q in Chinese Pharmaceutical Indu

14、stry （cont.） 當前中國醫(yī)藥工業(yè)中調(diào)試與確認的相關(guān)問題 （續(xù)）Unclear interfaces and poor communications of the different project parties led to considerable overlapping or missing of project works, commissioning integration with qualification is rare. 不同項目參與方節(jié)點不清，溝通不暢導(dǎo)致相當?shù)捻椖抗ぷ髦丿B或漏項, 罕有調(diào)試與確認進行整合。Due to lack of specialized C&

15、Q people, most of the C&Q jobs rely on sub-contractors or vendors, the jobs quality is not under control, and the owner or the EPC contractor has to pay extra charges for each equipment or system. 由于缺乏專業(yè)的調(diào)試與確認人員，大部分的調(diào)試與確認工作依賴于分包商或供應(yīng)商，工作質(zhì)量不可控，而業(yè)主或總承包商不得不為每一設(shè)備或系統(tǒng)付出額外的費用。2012 ISPE CHINA ANNUAL CONFEREN

16、CEIntroduction 導(dǎo)言Current Issues Relative to C&Q in Chinese Pharmaceutical Industry （cont.） 當前中國醫(yī)藥工業(yè)中調(diào)試與確認的相關(guān)問題 （續(xù)）Though several Q&V consultants available, the scope and standards of works are undetermined, and therefore both quantity and quality of their works are hard to evaluate. 盡管有數(shù)家確認與驗證咨詢服務(wù)提供

17、商，但工作范圍與標準不明確，因而工作的數(shù)量與質(zhì)量都很難評估。 Due to absence of SME in some disciplines , the Q&V consultants sometimes can only reveal the defects in the project, but fail to present the cost-effective solutions for them, especially when the GMP conflicts with local codes, e.g. fire fighting or EHS codes. 由于某些專業(yè)的

18、專家欠缺，確認與驗證咨詢服務(wù)提供商有時僅能揭示項目的某些缺陷，但不能給出相應(yīng)的經(jīng)濟有效的解決方案，尤其是在GMP與國內(nèi)規(guī)范，如消防、環(huán)保、職業(yè)安全衛(wèi)生規(guī)范發(fā)生沖突時。2012 ISPE CHINA ANNUAL CONFERENCEIntroduction 導(dǎo)言Gap to Current Good Practices of the International Pharmaceutical Industry 與當前國際醫(yī)藥工業(yè)良好實踐的差距Aspects 方面China 中國International 國際Marketing Environment市場環(huán)境Obvious demand, lim

19、ited investment, development required需求明顯但投入有限，需要培育Regular demand, worth to invest, mature and normative需求一般，認為投入值得，成熟、規(guī)范Professionals專業(yè)人員Limited quantity, inexperienced, discipline-absent 數(shù)量、經(jīng)驗有限，學(xué)科配套不齊全 Abundant, experienced, complete disciplines，high -cost 數(shù)量充足，經(jīng)驗豐富，學(xué)科齊全,費用昂貴Organization機構(gòu)Tempora

20、l, project based, lately involve 臨時、基于項目、后期介入Standing, multi-projects, life-cycle involved 常設(shè)，多項目，全程Implementation執(zhí)行Random, no strict procedure, absent or overlapping隨意，無嚴格程序，漏項或重疊Normative, strict procedure, integrity 規(guī)范、程序嚴格、過程完整Documentation文件Poor integrity , irregular, non-real-time，reference ab

21、sent 完整性差，不規(guī)范，非實時，引用失缺 Good integrity, normative, real-time, complete reference, credible完整性好，規(guī)范，實時，引用齊全可信Approach 方法Partly follows ISPE Baseline Guide 5僅部分參照ISPE調(diào)試與確認指南ASTM E2500 07+ISPE Baseline Guide + GAMP52012 ISPE CHINA ANNUAL CONFERENCEDefinition 定義Commissioning & qualification services integ

22、rated into the pharmaceutical project lifecycle（I-C&Q Services) are the valuable consulting services provided by a professional C&Q consultant to help owner or EPC contractor to implement the commissioning and qualifications of design, installation, operation, performance of facilities, systems, and

23、 equipments, and finally the process validation of the facilities of a pharmaceutical project by applying GEP, GMP principles and engineering experiences，beginning with developing the OPR and extending through all phases of project delivery and into operation and maintenance. 與制藥工程項目全過程相整合的調(diào)試與確認服務(wù)(I

24、-C&Q服務(wù)）系由專業(yè)調(diào)試與確認咨詢商提供有價值的咨詢服務(wù)，應(yīng)用GEP、GMP原則和工程經(jīng)驗，從形成業(yè)主項目需求開始擴展到項目交付、直到運行和維護等所有階段，提供有價值的咨詢服務(wù)，幫助業(yè)主或總承包商完成制藥工程項目中設(shè)施、系統(tǒng)、設(shè)備的調(diào)試以及設(shè)計、安裝、運行、性能等一系列確認乃至設(shè)施的工藝驗證等。Definition and Contents of I-C&Q Services I-C&Q服務(wù)的定義與內(nèi)容Definition (cont.)定義（續(xù)）When Does Commissioning Occur? 調(diào)試的時機Commissioning can begin during pre-de

25、sign, design, construction or building start-up. The process can offer significantly greater and more cost effective benefits when it begins during pre-design or early design. 調(diào)試可從設(shè)計前、設(shè)計、施工或開車的時候開始。當從設(shè)計前或者設(shè)計早期開始時，該過程能產(chǎn)生更大并更經(jīng)濟有效的效益。 Commissioning integration into qualification調(diào)試與確認的整合Commissioning ca

26、n support qualification if performed within a qualification regime. In this case, it is critical to define the over-all scope of the tests and verifications to be performed for a system, before starting any commissioning or qualification work. 當按確認的制度來進行時，調(diào)試可用以支持確認，關(guān)鍵是在開展調(diào)試與確認工作前，應(yīng)定義系統(tǒng)測試與查證的所有范圍。13D

27、efinition and Contents of I-C&Q Services I-C&Q服務(wù)的定義與內(nèi)容Pre-DesignDesignConstructionStart-UpOperations &MaintenanceTest &BalanceStart-up TestingDefinition (cont.)-Commissioning Span of Control 定義(續(xù))-調(diào)試跨度的控制Commissioning 設(shè)計前調(diào)試開車測試設(shè)計施工開車運行及維護測試及平衡Source（來源）: D. Colburn et al. (2003)I-C&QC&QRisk Manageme

28、nt 風險管理Design Review 設(shè)計審核Change Management 變更管理Product Knowledge生產(chǎn)知識Regulatory法規(guī) Company Quality公司質(zhì)量Process Knowledge工藝知識Good Engineering Practice良好工程規(guī)范Requirements需求Specification & Design規(guī)格與設(shè)計Verification確認Acceptance & Release驗收與放行Operations & CI運行及持續(xù)改進ASTM E2500-07: Standards for Specification, De

29、sign & Verification of Pharmaceutical & Biopharmaceutical Manufacturing Systems & EquipmentDefinition (cont.)-Flexible Approach ASTM E2500 定義(續(xù))-ASTM E2500 -07柔性方法15ISPE Baseline Guide 5 Design Inputs設(shè)計輸入 Impact Assessment 影響評估 Design Qualification 設(shè)計確認 Commissioning 調(diào)試 Multiple Trial Runs to Get Th

30、ings Right 多次試運行以達標 IQ, OQ, PQ and Acceptance Criteria IQ,OQ, PQ及接受標準 GEP scope and QA scope overlapped GEP和QA范圍重疊 Focused on Documentation Deliverables 注重關(guān)注文件 Rigid Change Management剛性的變更管理ASTM E2500 Design Inputs設(shè)計輸入 Design Review設(shè)計審核 Risk Mitigation降低風險 Critical Control Parameters Define Acceptan

31、ce Criteria 關(guān)鍵控制參數(shù)定義接受標準 Verification Testing確認測試 Performance Testing 性能測試 GEP scope and QA scope have clear boundary GEP和QA界限清晰 Process, Product Quality and Patient Safety工藝，產(chǎn)品質(zhì)量和病人安全 Quality by Design, Design Space and Continuous Improvement質(zhì)量源于設(shè)計，設(shè)計空間及持續(xù)改進Definition and Contents of I-C&Q Services

32、 I-C&Q服務(wù)的定義與內(nèi)容Definition (cont.)定義（續(xù)）Source（來源）: IT Pharma Validation Europe (2008)162012 ISPE CHINA ANNUAL CONFERENCEContents服務(wù)內(nèi)容Represents “owner “ as an objective advocate 作為目標宣傳者代表業(yè)主Guides the development of F-URS, URS 指導(dǎo)編制設(shè)施URS及系統(tǒng)URSOrganizes or attends gap analysis, impact assessment, risk ass

33、essment and DR or DQ組織或參加偏差分析、影響分析、風險評估以及設(shè)計審核或設(shè)計確認Reviews standards/strategies early in design 在設(shè)計階段審核標準/策略Develops the Cx Plan and VMP編制調(diào)試計劃及驗證總計劃Definition and Contents of I-C&Q Services I-C&Q服務(wù)的定義與內(nèi)容2012 ISPE CHINA ANNUAL CONFERENCEContents (cont.) 服務(wù)內(nèi)容（續(xù)）Develops Cx contract language for the A/E

34、 & Construction contracts 編制建筑/工程設(shè)計及施工合同中的調(diào)試條款Guides the Development Quality System Program and Implementation Plan 指導(dǎo)編制質(zhì)量體系程序及實施方案Guides the total C&Q process 指導(dǎo)調(diào)試、確認全過程Ensures implementation of selected measures identified in the OPR 確保業(yè)主項目需求中明確的選擇措施的實施Verifies minimum targets have been met 查證最低目標

35、已滿足Completes final C&Q report 完成最終調(diào)試、確認報告Definition and Contents of I-C&Q Services I-C&Q服務(wù)的定義與內(nèi)容2012 ISPE CHINA ANNUAL CONFERENCEContents (cont.) 服務(wù)內(nèi)容（續(xù)）Guides Computer System Validation指導(dǎo)計算機系統(tǒng)驗證Guides Analytical Instrument Qualification and Analytical Method Analysis指導(dǎo)分析儀器確認與分析方法驗證 Guides Cleaning,

36、 Sterilization, and Fumigation Validation指導(dǎo)清潔、滅菌、熏蒸驗證Guides the PV process, completes PV report 指導(dǎo)工藝驗證過程，完成工藝驗證報告Coordinates system testing and operator training 協(xié)調(diào)系統(tǒng)測試和操作人員培訓(xùn)Definition and Contents of I-C&Q Services I-C&Q服務(wù)的定義與內(nèi)容2012 ISPE CHINA ANNUAL CONFERENCE Service Packets Breakdown 服務(wù)工作包分解Gap

37、 analysis and URS development guidance偏差分析及設(shè)施用戶需求編制指導(dǎo)GMP review GMP審核System Impact Assessment and Validation Master Plan development 系統(tǒng)影響評估與驗證總計劃編制Quality system program and implementation plan development Guidance 質(zhì)量體系程序及實施方案編制指導(dǎo)Definition and Contents of I-C&Q Services I-C&Q服務(wù)的定義與內(nèi)容2012 ISPE CHINA

38、 ANNUAL CONFERENCE Service Packets Breakdown (cont.) 服務(wù)工作包分解 （續(xù)）Risk Analysis and S-E/URS SOP, VP development guidance 風險分析及設(shè)備/系統(tǒng)用戶需求、驗證計劃編制指導(dǎo)Commissioning Plan and Qualification Protocol development guidance調(diào)試計劃和確認方案編制指導(dǎo)Component Impact Assessment, Risk Assessment guidance and DQ 組件影響分析、風險分析指導(dǎo)與設(shè)計確認

39、IQ，OP，PQ guidance安裝確認、運行確認、性能確認指導(dǎo)Computer System Validation guidance計算機系統(tǒng)驗證指導(dǎo)Definition and Contents of I-C&Q Services I-C&Q服務(wù)的定義與內(nèi)容2012 ISPE CHINA ANNUAL CONFERENCE Service Packets Breakdown (cont.) 服務(wù)工作包分解 （續(xù)）Analytical Instrument Qualification and Analytical Method Validation Guide分析儀器確認與分析方法驗證指導(dǎo)

40、Cleaning, Sterilization, and Fumigation Validation guide 清潔、滅菌、熏蒸驗證指導(dǎo)Process Validation guide工藝驗證指導(dǎo)Definition and Contents of I-C&Q Services I-C&Q服務(wù)的定義與內(nèi)容2012 ISPE CHINA ANNUAL CONFERENCEServices Provider and Stakeholders 服務(wù)提供商及相關(guān)方The Qualified Service Team Structure 合格的服務(wù)團隊人員構(gòu)成Based on the project

41、scope, resource requirements, and the key stakeholders; 取決于項目的范圍、資源需求以及主要相關(guān)方;Experienced and professional in individual field; 在相應(yīng)領(lǐng)域具有經(jīng)驗和專業(yè)素養(yǎng)Need to understand the roles, responsibilities, and levels of authority; 應(yīng)能理解自身的角色、責任以及權(quán)力層次；Have excellent communication, planning, and coordination between di

42、fferent parties.與不同的項目參與方間有很好的溝通、計劃與協(xié)調(diào)。 2012 ISPE CHINA ANNUAL CONFERENCEServices Provider and Stakeholders 服務(wù)提供商及相關(guān)方The Qualified Service Team Structure (cont.) 合格的服務(wù)團隊人員構(gòu)成（續(xù)）Including but not limited to, 包括但不限于，Team leader 團隊領(lǐng)導(dǎo)Compliance and regulatory expert 合規(guī)和法規(guī)專家Mechanical C&Q engineer (HVAC,

43、utilities) 機械調(diào)試與確認工程師（暖通、公用）Process equipment/system C&Q engineer 工藝設(shè)備、工藝系統(tǒng)調(diào)試與確認工程師2012 ISPE CHINA ANNUAL CONFERENCEServices Provider and Stakeholders 服務(wù)提供商及相關(guān)方The Qualified Service Team Structure (cont.) 合格的服務(wù)團隊人員構(gòu)成（續(xù)）Computer system validation engineer (software and hardware) 計算機系統(tǒng)驗證工程師AMV enginee

44、r and process validation engineer 分析方法驗證工程師及工藝驗證工程師Cleaning，sterilization, and fumigation validation engineer 清潔，滅菌，熏蒸驗證工程師Document coordinator and technical writer文件協(xié)調(diào)控制員及技術(shù)文件編制人員 2012 ISPE CHINA ANNUAL CONFERENCEServices Provider and Stakeholders 服務(wù)提供商及相關(guān)方The Qualified Service Team Structure (cont

45、.) 合格的服務(wù)團隊人員構(gòu)成（續(xù)）Outsource support subject matter experts of compliance and regulatory, mechanical (HVAC, utilities), process & equipment, clean finishing, operation, QC/QA, QMS etc. 合規(guī)和法規(guī)、機械（暖通、公用）、工藝與設(shè)備、潔凈裝修、運行、質(zhì)量控制與質(zhì)量保證、質(zhì)量管理體系等外部學(xué)科問題支持專家。 2012 ISPE CHINA ANNUAL CONFERENCEOther Project Parties 其它項

46、目參與方 A/E consultants 工程設(shè)計Procurement 采購Construction 施工Project management 項目管理Commissioning leaders or coordinator from contractors and owner 承包商、業(yè)主調(diào)試負責人或協(xié)調(diào)員 Operations/Production, maintenance, R&D, EHS, QC, QA, Qualification &Validation from the owner 業(yè)主生產(chǎn)運行、維護、研發(fā)、環(huán)保及健康安全、QC、QA、確認與驗證等部門Services Prov

47、ider and Stakeholders 服務(wù)提供商及相關(guān)方2012 ISPE CHINA ANNUAL CONFERENCEThe Authorities 監(jiān)管部門Food & Drug Administration食品藥品監(jiān)督部門 Municipal planning & construction administration規(guī)劃、建設(shè)管理部門Environmental Protection環(huán)保部門Fire authority消防部門Safety Supervision Administration安全監(jiān)督部門Labor Protection 勞動保護部門Quality Supervis

48、ion 質(zhì)量監(jiān)督部門 Services Provider and Stakeholders 服務(wù)提供商及相關(guān)方2012 ISPE CHINA ANNUAL CONFERENCERegulatory Requirements 法規(guī)要求 Necessity必要性Source（來源）: R. E. Chew and D. Petko (2007)EU GMP Annex 15 and SFDA GMP Chap. 7 “Qualification and Validation” define the requirements. 歐盟GMP附錄15和中國GMP第七章“確認與驗證”有明確要求。Relat

49、ionship of ASTM Standard to GMP regulations and guidance documentsASTM標準與GMP法規(guī)和指南文件的關(guān)系日本美國歐盟諸如CFR 211.68 “設(shè)備應(yīng)按書面程序進行校驗、檢查、或核對以確保其恰當性能”等條款是確認的基礎(chǔ)ICH Q9 質(zhì)量風險管理可用來決定“確認”的范圍指導(dǎo)如何執(zhí)行ASTM標準的主要原理及基本原則闡明基于風險的查證（或確認）的原理及基本原則Benefits to the Owner 為業(yè)主帶來的好處Risk controlled earlier 風險及早得到控制Reduce time and cost to ac

50、hieve and maintain compliance降低項目完成所耗費用與時間并維持項目的合規(guī)性Reduce change orders during construction 減少施工過程的變更令Less waste & repetition 更少的浪費與重復(fù)Reduce project delays 較少項目推遲Shorten building turnover period 縮短建筑交付周期Validation team and QMS set up 建立驗證團隊和質(zhì)量管理體系 Earlier released and commercial manufacture 更早地通過認證并

51、投入商業(yè)生產(chǎn) Necessity必要性Benefits to the Owner (cont.) 為業(yè)主帶來的好處(續(xù)）Cost effective operation and maintenance經(jīng)濟高效的運行及維護Reduce equipment replacement 減少設(shè)備更換Better knowledge, understanding of systems 對系統(tǒng)更好的認識和理解Better trained operations staff 更好地培訓(xùn)運行團隊Operations and maintenance manuals are complete and submitte

52、d at project turnover. 運行及維護手冊完成并在項目交付時提交Necessity必要性Benefits to the Contractors對承包商的好處Better planning will result in improved installation 更好的計劃可導(dǎo)致安裝的改進More emphasis on quality control on what matters 對質(zhì)量控制更加強調(diào)Quicker resolution of problems (identify problems during QC) 更快地解決問題（在QC過程中界定問題）Increase

53、likelihood of completing project on schedule maximize profit 提高按時完成項目的可能性利潤最大化Reduce post-construction callbacks preserve profit 減少施工后召回保護利潤Necessity必要性Benefits to the Authorities 對監(jiān)管部門的好處Genuine ,valid and systemic documentations 文件真實、有效、系統(tǒng)Easy of inspection 便于檢查Genuine, credible records and trends

54、 真實可信的記錄與趨勢Easy of supervision 便于監(jiān)管Clear management programs, integral approvals in manufacturers site 廠商管理程序清晰，審批完整Easy of investigation afterwards便于事后追究Necessity必要性Implementation Flow of Pharmaceutical Project制藥工業(yè)項目實施流程Production Start有效投產(chǎn)Feasibility Study可行性研究Concept Design概念設(shè)計Procurement采購Constr

55、uction 施工Detail Engineering詳細設(shè)計SupportValidation驗證支持 C&Q 調(diào)試與確認Decision “GO”客戶決定工程繼續(xù)進行Basic + Ext.Basic Engineering基本擴充設(shè)計Final investment Decision 客戶做出最終投資決定Cost Estimate造價估算 20%Cost Estimate造價估算 10%Concept Phase 概念階段 Design Phase 設(shè)計階段Execution Phase 實施階段 Hand Over交付Validation Phase驗證階段MaintenanceCus

56、tomer Service維修/客戶服務(wù)Facility Management設(shè)施管理Second Opinion Value Engineering 修改/補充Implementation 實施 Workflow 工作流程Acknowledgement （感謝）: Instruction from Mr. D .W. Vincent F(設(shè)施)-URSGA偏差分析BOD設(shè)計基礎(chǔ)VMP驗證總計劃RA風險分析E/S(設(shè)備/系統(tǒng))-URSVP驗證計劃CSVFD/FS功能設(shè)計/說明DD/DS詳細設(shè)計/設(shè)計說明CP(FAT, SAT, etc.), Qual.Protocol 調(diào)試計劃及確認方案PQ性

57、能確認OQ運行確認IQ安裝確認Commissioning (FAT/SAT, etc.) Exec.調(diào)試（工廠/現(xiàn)場驗收測試等）執(zhí)行DQ設(shè)計確認Procurement& Construction采購施工CV清潔驗證Sterilization Validation滅菌驗證PV工藝驗證Medium Fill培養(yǎng)基灌裝Utility Qua/Val公用系統(tǒng)確認/驗證Fumigation Validation熏蒸驗證AIQ分析儀器確認CSV計算機系統(tǒng)驗證CSV計算機系統(tǒng)驗證CSV計算機系統(tǒng)驗證AMV分析方法驗證SIA系統(tǒng)影響評估GMP Rev.GMP審核Implementation 實施 Workfl

58、ow 工作流程 Acknowledgement （感謝）: Instruction from Mr. C.BachofenWorkflowa brief case study (WFI system) 工作流程 簡略的案例分析(注射用水系統(tǒng)）Specify the final users, capacity, standards，etc. to be followed for WFI. system in F-URS 在設(shè)施URS中明確注射用水系統(tǒng)的終端用戶、供應(yīng)能力以及遵循的標準等。Implement GA for the renovated systems. 對改造的系統(tǒng)進行偏差分析。De

59、velop the schematic design of WFI system (e.g. MB, PFD，main equipment list) in the BOD of the facility （design consultant). 在設(shè)施的設(shè)計基礎(chǔ)中進行 注射用水系統(tǒng)的方案設(shè)計（物料平衡、工藝流程圖,主要設(shè)備表等）(設(shè)計咨詢方）。Implementation 實施 Workflowa brief case study (WFI system)（cont.) 工作流程 簡略的案例分析(注射用水系統(tǒng)）(續(xù)）Implement the IA of the WFI system acc

60、ording to the criteria. 按照判據(jù)進行注射用水的影響評估 。Specify the level of C&Qs (including CSV) and the rationale of the system in VMP. 在驗證總計劃中闡明調(diào)試確認(包括計算機系統(tǒng)驗證）的程度及原因.Develop the URS of the system (including the C&Q requirement), VP based on RA. 在風險分析的基礎(chǔ)上編制系統(tǒng)的URS及驗證計劃.Implementation 實施 Workflowa brief case study