【文章內(nèi)容簡介】 or intended to be sold). For the purposes of this guidance, the termmercial manufacturing process does not include clinical trial or treatment IND material.，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(yàn)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(dú)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)范尚未公布，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cGMP要求約束。《FDA/ICH行業(yè)指南 Q7活性藥物成分良好生產(chǎn)規(guī)范指南（ICH）》對活性藥物成分的工藝驗(yàn)證進(jìn)行了討論，可在下述網(wǎng)址獲得。ICH Q7 第十二部分詳細(xì)描述了活性藥物成分工藝驗(yàn)證的原則。包含不具約束力的建議中文譯稿：北京大學(xué)藥物信息與工程研究中心 info@3Act6本指南不涵蓋下列類型產(chǎn)品：? A 類添加藥物產(chǎn)品或添加藥物飼料? 醫(yī)療器械5? 膳食補(bǔ)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 a submission.本指南沒有詳細(xì)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 (.,puter hardware and software interfaces), which are monly integrated into modern drugmanufacturing equipment. 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(yàn)證（即計(jì)算機(jī)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)備在內(nèi)的工藝驗(yàn)證有關(guān)。FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities.Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only asremendations, unless specific regulatory or statutory requirements are cited. The use of the word shouldin Agency guidances means that something is suggested or remended, but not required.FDA 的指南文件，包括本指南在內(nèi)，沒有規(guī)定依法強(qiáng)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(jī)構(gòu)目前對該主題的看法，應(yīng)該僅僅被視為建議。在本機(jī)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 Validation (the 1987 guidance).7 Since then, wehave obtained additional experience through our regulatory oversight that allows us to update ourremendations to industry on this topic. This revised guidance conveys FDA’s current thinking on processvalidation and is consistent with basic principles first introduced in the 1987 guidance. The revised guidancealso provides remendations that reflect some of the goals of FDA’s initiative entitled “Pharmaceutical5 Guidance on process validation for medical devices is provided in a separate document, Quality Management Systems –Process Validation, edition 2, available at ，《質(zhì)量管理體系工藝驗(yàn)證》，第二版，可在。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 at6．參見FDA 行業(yè)指南《擬用作移植的人體組織工藝流程驗(yàn)證》，可從以下網(wǎng)址獲得：包含不具約束力的建議中文譯稿：北京大學(xué)藥物信息與工程研究中心 info@4CGMPs for the 21st Century ― A RiskBased Approach,” particularly with regard to the use of technologicaladvances in pharmaceutical manufacturing, as well as implementation of modern risk management andquality system tools and 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(yàn)證一般原則指導(dǎo)原則》的指南（1987 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(yàn)。該修訂版指南傳達(dá)了FDA 目前對工藝驗(yàn)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(jì)制藥行業(yè)現(xiàn)行藥品生產(chǎn)管理規(guī)范——一種基于風(fēng)險的方法”計(jì)劃的若干目標(biāo)的建議，特別是關(guān)于藥品生產(chǎn)中技術(shù)進(jìn)步的應(yīng)用，以及對現(xiàn)代風(fēng)險管理和質(zhì)量體系的工具及概念的實(shí)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 validation 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 (a) and (a)).FDA 有權(quán)力和責(zé)任對由生產(chǎn)商實(shí)施的工藝驗(yàn)證進(jìn)行檢查和評估。用于驗(yàn)證制藥的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 （a）和（a）》)。A. Process Validation and Drug QualityA. 工藝驗(yàn)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 use. 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 inprocess and finishedproduct inspection or testing.? Each step of a manufacturing process is controlled to assure that the finished product meets all qualityattributes including specifications.有效的工藝驗(yàn)證對保證藥品質(zhì)量做出了重要貢獻(xiàn)。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(jì)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 andRadiological 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 remendations in that document, QualityManagement Systems – Process Validation, edition 2 (available on the Internet at ) 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(yàn)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(yàn)證》（第二版）（可從互聯(lián)網(wǎng)上獲得），對考慮藥物生產(chǎn)工藝也有用。8 See “Pharmaceutical cGMPS for the 21st Century — A RiskBased Approach: Second Progress Report and ImplementationPlan,” available atscGMPforDrugs/.8 參見《21 世紀(jì)制藥業(yè)現(xiàn)行藥品生產(chǎn)規(guī)范一種基于風(fēng)險的方法：第二份進(jìn)展報告實(shí)施計(jì)劃》，可從以下網(wǎng)址獲得：scGMPforDrugs/。包含不具約束力的建議中文譯稿：北京大學(xué)藥物信息與工程研究中心 info@5? 質(zhì)量不能僅通過生產(chǎn)中檢查或檢測以及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)格在內(nèi)所有質(zhì)量屬性。B. Approach to Process ValidationB. 工藝驗(yàn)證方法For purposes of this guidance, process validation is defined as the collection and evaluation of data, from theprocess design stage through mercial production, which establishes scientific evidence that a process i