FDA最新工藝驗證指導(dǎo)書

1、 . . 40/40 HYPERLINK :/ HYPERLINK :/ Guidance for Industry行業(yè)指南Process Validation: GeneralPrinciples and Practices工藝驗證：一般原則與規(guī)U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)Center

2、for Veterinary Medicine (CVM)January 2011Current Good Manufacturing Practices (CGMP)Revision 1美國衛(wèi)生與人類服務(wù)部食品藥品管理局藥物評價和研究中心（CDER）生物制品評價和研究中心（CBER）獸藥中心（CVM）2011年1月現(xiàn)行藥品質(zhì)量生產(chǎn)管理規(guī)（CGMP）修訂版1包含不具約束力的建議中文譯稿：大學(xué)藥物信息與工程研究中心Guidance for Industry行業(yè)指南Process Validation: GeneralPrinciples and Practices工藝驗證：一般原則與規(guī)Addit

3、ional copies are available from:Office of CommunicationsDivision of Drug Information, WO51, Room 220110903 New Hampshire Ave.Silver Spring, MD20993Phone: 301-796-3400; Fax: 301-847-8714and/orOffice of Communication, Outreach and Development, HFM-40Center for Biologics Evaluation a

4、nd ResearchFood and Drug Administration1401 Rockville Pike, Rockville, MD20852-1448(Tel) 800-835-4709 or 301-827-1800and/orCommunications Staff, HFV-12Center for Veterinary MedicineFood and Drug Administration7519 Standish Place,Rockville, MD20855(Tel) 240-276-9300./AnimalVeterinary/GuidanceC

5、omplianceEnforcement/GuidanceforIndustry/default.htm包含不具約束力的建議中文譯稿：大學(xué)藥物信息與工程研究中心另外的副本可從以下部門得到：馬里銀泉市新罕布什爾大道10193號2201室藥品信息處，對外信息辦公室，郵政編碼：20993：301-796-3400; ：301-847-8714/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm和/或馬里洛克維爾市洛克維爾大道1401號HFM-40 FDA生物制品評

6、價和研究中心對外信息、外聯(lián)與發(fā)展辦公室郵政編碼：20852-1448：800-835-4709 或301-827-1800./BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm和/或馬里洛克維爾市Standish Place 7519號食品藥品管理局獸藥中心HFV-12通訊處，郵政編碼：20885：240-276-9300./AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndus

7、try/default.htmU.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)Center for Veterinary Medicine (CVM)January 2011Current Good Manufacturing Practices (CGMP)Revision 1美國衛(wèi)生與人類服務(wù)部食品藥品管

8、理局藥物評估和研究中心（CDER）生物制品評估和研究中心（CBER）獸藥中心（CVM）2011年1月現(xiàn)行藥品質(zhì)量生產(chǎn)管理規(guī)（CGMP）修訂版1包含不具約束力的建議中文譯稿：大學(xué)藥物信息與工程研究中心Table of Contents目錄I. INTRODUCTION 1一. 簡介 1II. BACKGROUND 3二. 背景 3A. Process Validation and Drug Quality 4A. 工藝驗證與藥品質(zhì)量 4B. Approach to Process Validation 5B. 工藝驗證方法 5III. STATUTORY AND REGULATORY REQUI

9、REMENTS FOR PROCESS VALIDATION 7三. 對工藝驗證的法規(guī)和監(jiān)管要求 7IV. RECOMMENDATIONS 9四. 建議 9A. General Considerations for Process Validation 9A. 對工藝驗證的總體考慮 9B. Stage 1 - Process Design 10B.第一階段- 工藝設(shè)計 101. Building and Capturing Process Knowledge and Understanding 111. 建立和捕獲工藝知識與理解 112. Establishing a Strategy for

10、 Process Control 122. 建立工藝控制策略 12C. Stage 2 - Process Qualification 14C. 第二階段- 工藝確認 141. Design of a Facility and Qualification of Utilities and Equipment 141. 廠房設(shè)施設(shè)計以與公用設(shè)施與設(shè)備確認 142. Process Performance Qualification 162. 工藝性能確認 163. PPQ Protocol 173. 工藝性能確認方案 174. PPQ Protocol Execution and Report

11、194. 工藝性能確認執(zhí)行與報告 19D. Stage 3 - Continued Process Verification 20D. 第三階段- 持續(xù)工藝驗證 20V. CONCURRENT RELEASE OF PPQ BATCHES 22五. 工藝性能確認批次的同時放行 22VI. DOCUMENTATION 24六. 文件記錄 24VII. ANALYTICAL METHODOLOGY 24七. 分析方法 24GLOSSARY 26術(shù)語表 26REFERENCES 28參考資料 28包含不具約束力的建議中文譯稿：大學(xué)藥物信息與工程研究中心1Guidance for Industry1行

12、業(yè)指南1Process Validation: General Principles and Practices工藝驗證：一般原則與實施This guidance represents the Food and Drug Administrations (FDAs) current thinking on this topic. It doesnot create or confer any rights for or on any person and does not operate to bind FDA or the public. You canuse an alternative

13、approach if the approach satisfies the requirements of the applicable statutes andregulations. If you want to discuss an alternative approach, contact the FDA staff responsible forimplementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate numberlisted on the t

14、itle page of this guidance.本指南體現(xiàn)了食品藥品管理局（FDA）關(guān)于這一主題的最新見解。本指南不為任何人或?qū)θ魏稳瞬艅?chuàng)造或賦予任何權(quán)利，不起束縛FDA 或公眾的作用。如果替代方法能夠滿足適用法律、法規(guī)的要求，您可以使用替代方法。如果您希望討論一種替代性方法，請與負責(zé)執(zhí)行本指南的FDA 工作人員聯(lián)系。如果您不能確定相應(yīng)的FDA 工作人員，請撥打本指南標題頁所列的相應(yīng)。I. INTRODUCTION一. 簡介This guidance outlines the general principles and approaches that FDA considers app

15、ropriate elements ofprocess validation for the manufacture of human and animal drug and biological products, including activepharmaceutical ingredients (APIs or drug substances), collectively referred to in this guidance as drugs orproducts. This guidance incorporates principles and approaches that

16、all manufacturers can use to validatemanufacturing processes.本指南概述了FDA 認為是包括原料藥在的人與動物用藥和生物制品（在本指南中合稱為藥品或制品）生產(chǎn)工藝驗證相應(yīng)要素的一般原則和方法。該指南收編了所有生產(chǎn)商可用于驗證生產(chǎn)工藝的多種原則和方法。This guidance aligns process validation activities with a product lifecycle concept and with existing FDAguidance, including the FDA/Internationa

17、l Conferenceon Harmonisation (ICH) guidances for industry, Q8(R2)Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System.2Although this guidance does not repeat the concepts and principles explained in those guidances, FDAencourages the use of modern pharmaceuti

18、cal development concepts, quality risk management, and qualitysystems at all stages of the manufacturing process lifecycle.本指南將工藝驗證活動與產(chǎn)品生命周期概念和現(xiàn)有FDA 指南進行了對齊，包括FDA/人用藥1 This guidance has been prepared by the Division of Manufacturing and Product Quality, Center for Drug Evaluation andResearch (CDER),

19、 in cooperation with CDERs Office of Pharmaceutical Sciences, the Center for Biologics Evaluation andResearch (CBER), the Office of Regulatory Affairs (ORA) and the Center for Veterinary Medicine (CVM) at the Food and DrugAdministration.1.本指南由FDA 制造與產(chǎn)品質(zhì)量處、藥物評價與研究中心（CDER）與CDER 藥物科學(xué)辦公室、生物制品評價與研究中心（CBE

20、R）、監(jiān)管事物辦公室(ORA)和獸藥中心（CVM）合作編制。包含不具約束力的建議中文譯稿：大學(xué)藥物信息與工程研究中心2品注冊技術(shù)規(guī)國際協(xié)調(diào)會議(ICH)行業(yè)指南，Q8(R2)藥品開發(fā)、Q9質(zhì)量風(fēng)險管理和Q10藥品質(zhì)量體系。2 盡管本指南不復(fù)述那些指南解釋的概念或原則，但FDA 鼓勵在藥物工藝生命周期所有階段使用現(xiàn)代藥物開發(fā)概念、質(zhì)量風(fēng)險管理和質(zhì)量體系。The lifecycle concept links product and process development, qualification of the commercial manufacturingprocess,3 and mai

21、ntenance of the process in a state of control during routine commercial production. Thisguidance supports process improvement and innovation through sound science.生命周期概念銜接產(chǎn)品和工藝開發(fā)、商品化生產(chǎn)工藝確認3、以與日常商品化制造中處于受控狀態(tài)的過程維護。本指過可靠的科學(xué)為工藝改進和創(chuàng)新提供支持。This guidance covers the following categories of drugs: Human drugs

22、 Veterinary drugs Biological and biotechnology products Finished products and active pharmaceutical ingredients (APIs or drug substances)4 The drug constituent of a combination (drug and medical device) product本指南涵蓋下列類別的藥物： 人用藥 獸用藥 生物和生物技術(shù)制品 制劑產(chǎn)品和活性藥物成分（原料藥或藥用物質(zhì)）4 組合產(chǎn)品（藥物和醫(yī)療器械）的藥物組分This guidance doe

23、s not cover the following types of products: Type A medicated articles and medicated feed Medical devices5 Dietary supplements Human tissues intended for transplantation regulated under section 361 of the Public Health Service2To make sure you have the most recent version of a guidance, check the CD

24、ER guidance page /Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, the CBER guidance page /BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm,or the CVM guidance page /AnimalVeterinary/GuidanceComplianceEnforcement/G

25、uidanceforIndustry/default.htm2.為確保您能得到指南的最新版本，請核對藥物評價與研究中心（CDER）網(wǎng)頁，網(wǎng)址為：./Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm,生物制品評價與研究中心（CBER）指南網(wǎng)頁，網(wǎng)址為：./BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm,或獸藥中心指南網(wǎng)頁，網(wǎng)址為：./AnimalVe

26、terinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm3 In this guidance, the term commercial manufacturing process refers to the manufacturing process resulting in commercialproduct (i.e., drug that is marketed, distributed, and sold or intended to be sold). For the purposes of this

27、 guidance, the termcommercial manufacturing process does not include clinical trial or treatment IND material.3.本指南中，商品化生產(chǎn)工藝這一專業(yè)名詞指生產(chǎn)出商品化產(chǎn)品的生產(chǎn)工藝（即用于經(jīng)銷、流通、出售或擬出售的藥品）。就本指南而言，商品化生產(chǎn)工藝這一專業(yè)名詞不包括臨床試驗或用于治療的研究型藥物（IND）材料。4截止本指南發(fā)布之日，單獨針對藥物組分如有效藥用成分(藥用物質(zhì))和中間體的現(xiàn)行藥品生產(chǎn)質(zhì)量管理規(guī)尚未公布，但這些組分受聯(lián)邦食品、藥品和化妝品法第501節(jié)(a)(2)(B) 法定c

28、GMP要求約束。./Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.FDA/ICH行業(yè)指南Q7活性藥物成分良好生產(chǎn)規(guī)指南（ICH）對活性藥物成分的工藝驗證進行了討論，可在下述網(wǎng)址獲得，./Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 。ICH Q7 第十二部分詳細描述了活性藥物成分工藝驗證的原則。包含不具約束力的建議中文譯稿：大學(xué)藥物信息與工程研究中心3Act6本指南不涵蓋下列類型產(chǎn)品： A

29、 類添加藥物產(chǎn)品或添加藥物飼料 醫(yī)療器械5 膳食補充劑 受公共衛(wèi)生服務(wù)法第361 節(jié)監(jiān)管的擬用于移植的人體組織6This guidance does not specify what information should be included as part of a regulatory submission.Interested persons can refer to the appropriate guidance or contact the appropriate Center in determining thetype of information to include in

30、 a submission.本指南沒有詳細說明哪些信息應(yīng)該包括在監(jiān)管提交文件部分中。有興趣的人士可以參考相應(yīng)指南或聯(lián)系相應(yīng)中心以確定應(yīng)包括在提交文件中的信息類型。This guidance also does not specifically discuss the validation of automated process control systems (i.e.,computer hardware and software interfaces), which are commonly integrated into modern drugmanufacturing equipmen

31、t. This guidance is relevant, however, to the validation of processes that includeautomated equipment in processing.本指南也沒有具體討論自動化工藝控制系統(tǒng)驗證（即計算機硬件和軟件界面），這些自動化控制系統(tǒng)通常集成在現(xiàn)代化藥物生產(chǎn)設(shè)備中。然而，該指南與包括工藝過程自動設(shè)備在的工藝驗證有關(guān)。FDAs guidance documents, including this guidance, do not establish legally enforceable responsibil

32、ities.Instead, guidances describe the Agencys current thinking on a topic and should be viewed only asrecommendations, unless specific regulatory or statutory requirements are cited. The use of the word shouldin Agency guidances means that something is suggested or recommended, but not required.FDA

33、的指南文件，包括本指南在，沒有規(guī)定依法強制執(zhí)行責(zé)任。相反，除非引述具體的監(jiān)管或法規(guī)要求，指南描述的是本機構(gòu)目前對該主題的看法，應(yīng)該僅僅被視為建議。在本機構(gòu)指南中所使用的“應(yīng)該”一詞，指建議或推薦某事，并非必須的。II. BACKGROUND二. 背景In the Federal Register of May 11, 1987 (52 FR 17638), FDA issued a notice announcing the availability of aguidance entitled Guideline on General Principles of Process Validat

34、ion (the 1987 guidance).7 Since then, wehave obtained additional experience through our regulatory oversight that allows us to update ourrecommendations to industry on this topic. This revised guidance conveys FDAs current thinking on processvalidation and is consistent with basic principles first i

35、ntroduced in the 1987 guidance. The revised guidancealso provides recommendations that reflect some of the goals of FDAs initiative entitled “Pharmaceutical5 Guidance on process validation for medical devices is provided in a separate document, Quality Management Systems Process Validation, edition

36、2, available at ./sg3/sg3-final.html. See infra note 6.5.醫(yī)療儀器工藝驗證指南以一個單獨文件的形式提供，質(zhì)量管理體系工藝驗證，第二版，可在./sg3/sg3-final.html 獲得。參見下文中的注釋6。6 See the FDA guidance for industry, Validation of Procedures for Processing of Human Tissues Intended for Transplantation,available on the Internet at.f

37、/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.6參見FDA 行業(yè)指南擬用作移植的人體組織工藝流程驗證，可從以下網(wǎng)址獲得：./BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm包含不具約束力的建議中文譯稿：大學(xué)藥物信息與工程研究中心4CGMPs for the 21st Century A Risk-Based Approach,

38、” particularly with regard to the use of technologicaladvances in pharmaceutical manufacturing, as well as implementation of modern risk management andquality system tools and concepts.8 This revised guidance replaces the 1987 guidance.1987 年5 月11 日，F(xiàn)DA 在聯(lián)邦公告(52 FR 17638)上發(fā)布公告，宣布題為工藝驗證一般原則指導(dǎo)原則的指南（19

39、87 年版指南）面世。7 從那時起，通過監(jiān)管監(jiān)督，我們能夠在此主題上更新對業(yè)界的建議，使我們獲得了更多經(jīng)驗。該修訂版指南傳達了FDA 目前對工藝驗證的看法，并與1987 年版指南首次提出的基本原則相一致。修訂版指南還提出了一些反映FDA“21 世紀制藥行業(yè)現(xiàn)行藥品生產(chǎn)管理規(guī)一種基于風(fēng)險的方法”計劃的若干目標的建議，特別是關(guān)于藥品生產(chǎn)術(shù)進步的應(yīng)用，以與對現(xiàn)代風(fēng)險管理和質(zhì)量體系的工具與概念的實施。8 該修訂版指南取代1987 年版指南。FDA has the authority and responsibility to inspect and evaluate process validatio

40、n performed bymanufacturers. The CGMP regulations for validating pharmaceutical (drug) manufacturing require that drugproducts be produced with a high degree of assurance of meeting all the attributes they are intended topossess (21 CFR 211.100(a) and 211.110(a).FDA 有權(quán)力和責(zé)任對由生產(chǎn)商實施的工藝驗證進行檢查和評估。用于驗證制藥的

41、cGMP 法規(guī)要求藥品在高度保證符合所有預(yù)期擁有屬性的情況下生產(chǎn)(聯(lián)邦法規(guī)21 編122.100（a）和211.110（a）)。A. Process Validation and Drug QualityA. 工藝驗證與藥品質(zhì)量Effective process validation contributes significantly to assuring drug quality. The basic principle of qualityassurance is that a drug should be produced that is fit for its intended us

42、e. This principle incorporates theunderstanding that the following conditions exist: Quality, safety, and efficacy are designed or built into the product. Quality cannot be adequately assured merely by in-process and finished-product inspection or testing. Each step of a manufacturing process is con

43、trolled to assure that the finished product meets all qualityattributes including specifications.有效的工藝驗證對保證藥品質(zhì)量做出了重要貢獻。質(zhì)量保證的基本原則在于生產(chǎn)出來的藥品符合其預(yù)定用途。該原則包括對存在下列情況的理解： 質(zhì)量、安全性和功效被設(shè)計或構(gòu)建于產(chǎn)品之中。7 The 1987 guidance was prepared by a working group that included representation from the Center for Devices andRadio

44、logical Health (CDRH). Since that time, CDRH elected to reference a process validation guidance prepared incooperation with the Global Harmonization Task Force (GHTF). The principles and recommendations in that document, QualityManagement Systems Process Validation, edition 2 (available on the Inter

45、net at ./sg3/sg3-final.html) are alsouseful to consider for drug manufacturing processes.7 從那時以來，CDRH 選擇與全球協(xié)調(diào)工作組（the Global Harmonization Task Force (GHTF)）合作編制的工藝驗證指南作為參考。該文件的原則和建議，質(zhì)量管理體系工藝驗證（第二版）（可從互聯(lián)網(wǎng)上獲得./sg3/sg3-final.html），對考慮藥物生產(chǎn)工藝也有用。8 See “Pharmaceutical cGMPS for the 21st Ce

46、ntury A Risk-Based Approach: Second Progress Report and ImplementationPlan,” available /Drugs/DevelopmentApprovalProcess/Manufacturing/QuestionsandAnswersonCurrentGoodManufacturingPracticescGMPforDrugs/ucm071836.htm.8 參見21 世紀制藥業(yè)現(xiàn)行藥品生產(chǎn)規(guī)一種基于風(fēng)險的方法：第二份進展報告實施計劃，可從以下網(wǎng)址獲得：./Drugs/Developme

47、ntApprovalProcess/Manufacturing/QuestionsandAnswersonCurrentGoodManufacturingPracticescGMPforDrugs/ucm071836.htm。包含不具約束力的建議中文譯稿：大學(xué)藥物信息與工程研究中心5 質(zhì)量不能僅通過生產(chǎn)中檢查或檢測以與成品檢查或檢測給予充分保證。 生產(chǎn)工藝的每一步均予以控制，確保成品符合包括規(guī)格在所有質(zhì)量屬性。B. Approach to Process ValidationB. 工藝驗證方法For purposes of this guidance, process validation i

48、s defined as the collection and evaluation of data, from theprocess design stage through commercial production, which establishes scientific evidence that a process iscapable of consistently delivering quality product. Process validation involves a series of activities takingplace over the lifecycle

49、 of the product and process. This guidance describes process validation activities inthree stages.就本指南而言，工藝驗證被定義為從工藝設(shè)計階段到商業(yè)生產(chǎn)的整個過程中，對數(shù)據(jù)進行收集和評價，建立能夠使工藝能夠始終如一地傳遞到優(yōu)質(zhì)產(chǎn)品中的科學(xué)證據(jù)。工藝驗證涉與整個產(chǎn)品生命周期和生產(chǎn)中發(fā)生的一系列活動。本指南分三個階段對工藝驗證進行說明。 Stage 1 Process Design: The commercial manufacturing process is defined during this

50、 stagebased on knowledge gained through development and scale-up activities. 第一階段工藝設(shè)計: 在開發(fā)和放大活動過程中獲得的知識基礎(chǔ)上，在此階段對商品化制造工藝進行定義。 Stage 2 Process Qualification: During this stage, the process design is evaluated todetermine if the process is capable of reproducible commercial manufacturing. 第二階段工藝確認: 在此階

51、段，對工藝設(shè)計進行評估，以確認工藝是否具備可重現(xiàn)的商品化制造能力。 Stage 3 Continued Process Verification: Ongoing assurance is gained during routineproduction that the process remains in a state of control. 第三階段持續(xù)工藝核實:在日常生產(chǎn)中獲得工藝保持處于受控狀態(tài)的持續(xù)和不斷發(fā)展的保證。This guidance describes activities typical of each stage, but in practice, some acti

52、vities might occur inmultiple stages.本指南對每個階段的典型活動進行了說明，但在實踐中，有些活動可能發(fā)生于多個階段。Before any batch from the process is commercially distributed for use by consumers, a manufacturer shouldhave gained a high degree of assurance in the performance of the manufacturing process such that it willconsistently pr

53、oduce APIs and drug products meeting those attributes relating to identity, strength, quality,purity, and potency. The assurance should be obtained from objective information and data from laboratory-,pilot-, and/or commercial-scale studies. Information and data should demonstrate that the commercia

54、lmanufacturing process is capable of consistently producing acceptable quality products within commercialmanufacturing conditions.經(jīng)工藝生產(chǎn)出任何批次產(chǎn)品經(jīng)過商業(yè)流通給消費者使用之前，生產(chǎn)商應(yīng)在生產(chǎn)工藝性能方面取得高度保證，以始終如一地生產(chǎn)出滿足與鑒別、含量、質(zhì)量、純度和效價相關(guān)的那些屬性的原料藥和藥品。這些保證應(yīng)該從來自于實驗室小試、中試、和/或商品化大生產(chǎn)研究的客觀信息或數(shù)據(jù)獲得。信息和數(shù)據(jù)應(yīng)該顯示，商品化制造工藝應(yīng)能在商品化制造條件下始終如包含不具約束力的建議

55、中文譯稿：大學(xué)藥物信息與工程研究中心6一地生產(chǎn)出合格的優(yōu)質(zhì)產(chǎn)品。A successful validation program depends upon information and knowledge from product and processdevelopment. This knowledge and understanding is the basis for establishing an approach to control of themanufacturing process that results in products with the desired qual

56、ity attributes. Manufacturers should:一個成功的驗證方案取決于來自產(chǎn)品和工藝開發(fā)的知識。這種知識和理解是建立能夠生產(chǎn)出具備期望得到的質(zhì)量屬性產(chǎn)品生產(chǎn)工藝控制方法的基礎(chǔ)。制造商應(yīng)該： Understand the sources of variation 了解變異來源 Detect the presence and degree of variation 探測變異存在和程度 Understand the impact of variation on the process and ultimately on product attributes 了解變異對工藝

57、和最終對產(chǎn)品屬性的影響 Control the variation in a manner commensurate with the risk it represents to the process andproduct 用與代表工藝與產(chǎn)品風(fēng)險相稱的方式控制變異。Each manufacturer should judge whether it has gained sufficient understanding to provide a high degree ofassurance in its manufacturing process to justify commercial

58、distribution of the manufacturing process andassociated variations may not lead to adequate assurance of quality. After establishing and confirming theprocess, manufacturers must maintain the process in a state of control over the life of the process, even asmaterials, equipment, production environm

59、ent, personnel, and manufacturing procedures change.9所有生產(chǎn)商均應(yīng)判斷是否已經(jīng)對生產(chǎn)工藝提供高度保證獲得足夠理解，為產(chǎn)品商業(yè)流通提供保證。只是專注于確認努力，而忽略對生產(chǎn)工藝和相關(guān)變異的關(guān)注，不能導(dǎo)致對質(zhì)量的充分保證。在建立和確認工藝之后，生產(chǎn)商必須保持工藝在工藝生命期處于受控狀態(tài)，即便是材料、設(shè)備、生產(chǎn)環(huán)境、人員和生產(chǎn)工序發(fā)生變更的情況下。9Manufacturers should use ongoing programs to collect and analyze product and process data to evaluate thestate of control of the process. These programs may identify process or product problems or opportunities forprocess improvements that can be evaluated and implemented through some of the activities described inStages 1 and 2.生產(chǎn)商應(yīng)使用持續(xù)和不斷發(fā)展的方案收集分析產(chǎn)品和工藝數(shù)據(jù)，對工藝受控狀態(tài)進行評估。這些方案可以確定工藝或產(chǎn)品問題，或找出工藝改善的適當(dāng)時機