原料藥GMP指南(中英文對(duì)照)

1、v1.0可編輯可修改12目錄1. 簡(jiǎn)介目的法規(guī)的適用性范圍2. 質(zhì)量管理總則質(zhì)量部門(mén)的責(zé)任生產(chǎn)作業(yè)的職責(zé)內(nèi)部審計(jì)（自檢）產(chǎn)品質(zhì)量審核3. 人員3. 人員的資質(zhì)人員衛(wèi)生顧問(wèn)4. 建筑和設(shè)施設(shè)計(jì)和結(jié)構(gòu)of the Quality forUni t(s)Product ionQ7a （中英文對(duì)照）FDA原料藥GMP指南Table of Contents1. INTRODUCTIONObjectiveRegulatory ApplicabilityScope2. QUALITY MANAGEMENTPrin ciplesResp on sibilitiesResp on sibilityActivit

2、iesInternal Audits (Self In spect ion)Product Quality Review3. PERSONNELPersonnel Qualificati onsPers onnel Hygie neCon sulta nts4. BUILDINGS AND FACILITIESDesig n and Con struct ionv1.0可編輯可修改UtilitiesWaterCon tai nmentLighti ngSewage and Refuse公用設(shè)施水限制照明排污和垃圾衛(wèi)生和保養(yǎng)5. PROCESS EQUIPMENT5.工藝設(shè)備Desig n an

3、d Con struct ion設(shè)計(jì)和結(jié)構(gòu)Equipme nt Maintenance and Clea ning設(shè)備保養(yǎng)和清潔Calibratio n校驗(yàn)Computerized Systems計(jì)算機(jī)控制系統(tǒng)6. DOCUMENTATION AND RECORDS6.文件和記錄Docume ntati onSystemand 文件系統(tǒng)和質(zhì)量標(biāo)準(zhǔn)San itati on and Maintenance23Specificati ons設(shè)備的清潔和使用記錄Equipme nt clea ning and Use RecordRecordsof Raw Materials,原料、中間體、原料藥的標(biāo)

4、簽和包裝材料的In termediates,APILabel ingand 記錄Packag ing MaterialsMaster Productio nIn structi ons(Master生產(chǎn)工藝規(guī)程（主生產(chǎn)和控制記錄）（Batch批生產(chǎn)記錄（批生產(chǎn)和控制記錄）實(shí)驗(yàn)室控制記錄批生產(chǎn)記錄審核Product ion and Con trol Records)BatchProduct ionRecordsProduct ion and Con trol Records)Laboratory Con trol RecordsBatch Producti on Record Reviewv1.

5、0可編輯可修改7. MATERIALS MANAGEMENT7.物料管理Gen eral Con trols控制通則Receipt and Quara ntine接收和待驗(yàn)Sampli ngand Testi ngof Incoming進(jìn)廠物料的取樣與測(cè)試Product ion MaterialsStorage儲(chǔ)存Re-evaluati on復(fù)驗(yàn)8. PRODUCTION AND IN-PROCESS CONTROLS 8.生產(chǎn)和過(guò)程控制Product ion Operati ons生產(chǎn)操作Time Limits時(shí)限In-process Sampli ng and Con trols工序取樣和

6、控制Ble nding Batches of In termediatesor中間體或原料藥的混批APIsCon tam in ati on Con trol污染控制9. PACKAGIN(ANDIDENTIFICATION LABELING9.原料藥和中間體的包裝和貼簽OF APIs AND INTERMEDIATESGen eral總則Packaging Materials包裝材料Label Issua nee and Con trol標(biāo)簽發(fā)放與控制Packagi ng and Labeli ng Operati ons包裝和貼簽操作10. STORAGE AND DISTRIBUTION

7、10.儲(chǔ)存和分發(fā)Warehousi ng Procedures入庫(kù)程序33v1.0可編輯可修改45Distributi on Procedures分發(fā)程序11. LABORATORY CONTROLS11.實(shí)驗(yàn)室控制Gen eral Con trols控制通則Testi ng of In termediates and APIs中間體和原料藥的測(cè)試Validati on of An alytical Procedures分析方法的驗(yàn)證Certificates of An alysis分析報(bào)告單Stability Monitoring of APIs原料藥的穩(wěn)定性監(jiān)測(cè)Expiry and Ret

8、est Dat ing有效期和復(fù)驗(yàn)期Reserve/Rete nti on Samples留樣12. VALIDATION12.驗(yàn)證Validation Policy驗(yàn)證方針Validati on Docume ntati on驗(yàn)證文件Qualificatio n確認(rèn)Approaches to Process Validati onProcess Validati on ProgramPeriodic Review of Validated SystemsClea ning Validati onValidation of An alytical Methods工藝驗(yàn)證的方法工藝驗(yàn)證的程序驗(yàn)證

9、系統(tǒng)的定期審核清洗驗(yàn)證分析方法的驗(yàn)證13.變更的控制13. CHANGE CONTROL14. REJECTION AND RE-USE OF MATERIALS 14.拒收和物料的再利用拒收返工Rejectio nReprocess ingv1.0可編輯可修改Reworki ngRecovery of Materials and SolventsReturns重新加工物料與溶劑的回收退貨5515. COMPLAINTS AND RECALLS15.投訴與召回16. CONTRACTMANUFACTURERSNCLUDING 16.協(xié)議生產(chǎn)商（包括實(shí)驗(yàn)室）LABORATORIES）REPACK

10、ERS,AND包裝者和重新貼簽者17. AGENTS, BROKERS, TRADERS,DISTRIBUTORS,RELABELLERSApplicabilityTraceability of Distributed APIs andIn termediatesQuality Man ageme ntRepackaging, Relabeling, and Holding ofAPIs and In termediatesStabilityTran sfer of In formatio nHan dli ng of Complai nts and RecallsHan dli ng of

11、Retur ns18. Specific Guida nee for APIsManu facturedbyCellCulture/Ferme ntati on17. 代理商、經(jīng)紀(jì)人、貿(mào)易商、經(jīng)銷(xiāo)商、重新適用性已分發(fā)的原料藥和中間體的可追溯性質(zhì)里官理原料藥和中間體的重新包裝、重新貼簽和待檢穩(wěn)定性信息的傳達(dá)投訴和召回的處理退貨的處理18. 用細(xì)胞繁殖/發(fā)酵生產(chǎn)的原料藥的特殊指南v1.0可編輯可修改Gen eral總則CellBank Maintenance and Record細(xì)胞庫(kù)的維護(hù)和記錄的保存Keep ingCell Culture/Ferme ntati on細(xì)胞繁殖/發(fā)酵Harves

12、ti ng,Isolati onand Purificati on收取、分離和精制Viral Removal/In activati on steps病毒的去除/滅活步驟19. APIs for Use in Clinical Trials19.用于臨床研究的原料藥Gen eral總則Quality質(zhì)量Equipment and Facilities設(shè)備和設(shè)施Control of Raw Materials原料的控制Product ion生產(chǎn)Validati on驗(yàn)證Changes變更Laboratory Con trols實(shí)驗(yàn)室控制Docume ntati on文件20. Glossary2

13、0.術(shù)語(yǔ)66v1.0可編輯可修改Q7a GMP Guida nee for APIsQ7a原料藥的GMpf南771. INTRODUCTIONObjectiveThis document is intended to provide guidanee regardinggood manufacturingpractice (GMP) for the manu facturi ng of active pharmaceutical in gredie nts (APIs) under an appropriate system for managing1.簡(jiǎn)介目的本文件旨在為在合適的質(zhì)量管理體系

14、下制造 活性藥用成分（以下稱(chēng)原料藥）提供有關(guān)優(yōu) 良藥品生產(chǎn)管理規(guī)范（GMP提供指南。它也 著眼于幫助確保原料藥符合其旨在達(dá)到或表 明擁有的質(zhì)量與純度要求。quality. It is also inten dedto helpensure that APIs meet the quality and purity characteristicsthat theypurport, or are represented, to possess.In this guidanee, the term manufacturing is defined to include all operations

15、of receipt of materials, producti on, packag ing, repackag ing,labeli ng,relabeli ng, qualitycon trol,release,storage and distribution of APIs and the本指南中所指的“制造”包括物料接收、生 產(chǎn)、包裝、重新包裝、貼簽、重新貼簽、質(zhì) 量控制、放行、原料藥的儲(chǔ)存和分發(fā)及其相 關(guān)控制的所有操作。本指南中，“應(yīng)當(dāng)”一詞表示希望采用的建議，除非證明其不適用或 者可用一種已證明有同等或更高質(zhì)量保證水related con trols. In this guid

16、a nee, the 平的供選物來(lái)替代。本指南中的“現(xiàn)行優(yōu)良v1.0可編輯可修改term should identifies recommendations生產(chǎn)管理規(guī)范（cGMp”和“優(yōu)良生產(chǎn)管理規(guī)that,when followed, willensure范（GMp” 是等同的。complia neewith CGMPs. An alter nativeapproach may be used if such approachsatisfies therequireme ntsof theapplicable statues. For the purposes ofthis guidanee

17、, the terms currentgoodmanu facturi ngpractices and goodmanu facturi ng practicesare equivale nt.88The guida nee as a whole does not coversafety aspects for the personnel engagedin manufacturing,nor aspects related to本指南在總體上未涉及生產(chǎn)人員的安全冋題，亦不包括環(huán)保方面的內(nèi)容。這方面的管理是生產(chǎn)者固有的責(zé)任，也是國(guó)家法律規(guī)定protect ingthe environment.

18、 These 的。con trols are in here nt resp on sibilitiesof the manu facturer and are gover ned by n atio nal laws.This guida nee is not inten ded to defi ne registration and/or filing requirements or modify pharmacopoeial requireme nts.This guidanee does not affect the ability of the resp on sible regul

19、atory age ncy to establish specificregistrati on /fili ngrequireme nts regard ing APIs within the con text ofmarket in g/ma nu facturi ng 本指南未規(guī)定注冊(cè)/歸檔的要求、或修改藥典 的要求。本指南不影響負(fù)責(zé)藥政審理部門(mén)在 原料藥上市/制造授權(quán)或藥品申請(qǐng)方面建立 特定注冊(cè)/歸檔要求的能力。注冊(cè)/歸檔的所 有承諾必須做到。v1.0可編輯可修改authorizations or drug applications.Allcommitme nts inregistra

20、ti on /fili ng法規(guī)的適用性may在世界范圍內(nèi)對(duì)原料藥的法定定義是各不相 as同的。當(dāng)某種物料在其制造或用于藥品的地 區(qū)或國(guó)家被稱(chēng)為原料藥，就應(yīng)該按照本指南 進(jìn)行生產(chǎn)。docume nts should be met.Regulatory ApplicabilityWithin the world community, materials vary as to their legal classification an API. When a material is classified as an API in the regi on or country in which it

21、 is manufacturedor used in a drugproduct, it should be manu factured accord ing to this guida nee.范圍本文件適用于人用藥品（醫(yī)療用品）所含原 料藥的生產(chǎn)。它適用于無(wú)菌原料藥在滅菌前 的步驟。本指南不包括無(wú)菌原料藥的消毒和 滅菌工藝，但是，應(yīng)當(dāng)符合地方當(dāng)局所規(guī)定 的藥品（醫(yī)療用品）生產(chǎn)的 GMP指南。ScopeThis guidanee applies to the manufacture of APIs for use in human drug (medicinal) products. It

22、applies to the manufacture of sterile APIs only up to the point immediately prior to the APIs being rendered sterile. The sterilization and aseptic process ing of sterile APIs are not covered by this guidanee, but should be performed inaccordaneewith GMPguida nces for drug (medici nal) products as d

23、efined by local authorities.99v1.0可編輯可修改This guida nee covers APIs that are manu faeturedby chemicalsyn thesis,extract ion, cell culture/ferme ntatio n, recovery from naturalsources, or anycomb in ati on of these processes. Specific guida nee for APIs manu factured by cell culture/ferme ntati onis d

24、escribed inSection 18.This guida nee excludes all vacci nes, whole cells, whole blood and plasma, blood and plasma derivatives (plasma fraction ati on), and gene therapy APIs.However, it does in clude APIs that are produced using blood or plasma as raw materials. Note that cell substrates (mammalia

25、n, pla nt, in sect or microbial cells, tissue or animal sources including transgenicanimals) and early processsteps may be subject to GMP but are not covered by this guida nee. In additi on, the guida nee does not apply to medical gases, bulk-packaged drug (medici nal) products ., tablets or capsule

26、s in bulk contain ers), or radiopharmaceuticals.本文件適用于通過(guò)化學(xué)合成、提取、細(xì)胞培養(yǎng)/發(fā)酵，通過(guò)從自然資源回收，或通過(guò)這些 工藝的結(jié)合而得到的原料藥。通過(guò)細(xì)胞培養(yǎng)/ 發(fā)酵生產(chǎn)的原料藥的特殊指南則在第18章論述。本指南不包括所有疫苗、完整細(xì)胞、全 血和血漿、全血和血漿的衍生物（血漿成分） 和基因治療的原料藥。但是卻包括以血或血 漿為原材料生產(chǎn)的原料藥。值得注意的是細(xì) 胞培養(yǎng)基（哺乳動(dòng)物、植物、昆蟲(chóng)或微生物 的細(xì)胞、組織或動(dòng)物源包括轉(zhuǎn)基因動(dòng)物）和 前期生產(chǎn)可能應(yīng)遵循 GMP規(guī)范，但不包括在 本指南之內(nèi)。另外，本指南不適用于醫(yī)用氣 體、散裝的制劑藥

27、（例如，散裝的片劑和膠 囊）和放射性藥物的生產(chǎn)。1010v1.0可編輯可修改Secti on 19 contains guida nee that only applies to the manufacture of APIs used in the product ionof drug (medici nal) 第19章的指南只適用于用在藥品 （醫(yī)療用品） 生產(chǎn)中的原料藥制造，特別是臨床實(shí)驗(yàn)用藥（研究用醫(yī)療產(chǎn)品）的原料藥制造。1111productsspecificallyfor clinicaltrials(in vestigati onalmedici nalproducts).An A

28、PI startingmaterialis a raw原料藥的起始物料”是指一種原料、中間material, an in termediate,or an API that體或原料藥，用來(lái)生產(chǎn)一種原料藥，或者以is used in the producti on of an API andthat is incorporatedas a significantstructural fragment into the structure of the API. An API start ing material can be an article of commerce, a material

29、主要結(jié)構(gòu)單元的形式被結(jié)合進(jìn)原料藥結(jié)構(gòu) 中。原料藥的起始物料可能是在市場(chǎng)上有售、 能夠通過(guò)合同或商業(yè)協(xié)議從一個(gè)或多個(gè)供應(yīng) 商處購(gòu)得，或由生產(chǎn)廠家自制。原料藥的起 始物料一般來(lái)說(shuō)有特定的化學(xué)特性和結(jié)構(gòu)。purchased from one or more suppliers un der con tract or commercial agreeme nt, or producedin-house.API start ingmaterialsno rmally have defi ned chemicalproperties and structure.The company should des

30、ignate and document the rati on alefor the point at whichproduct ion of the API beg ins. For synthetic processes, this is known as the point at which API starting materials are en tered into the process. For other 生產(chǎn)廠商要指定并用書(shū)面文件說(shuō)明原料藥的 生產(chǎn)從何處開(kāi)始的理論依據(jù)。對(duì)于合成工藝 而言，就是“原料藥的起始物料”進(jìn)入工藝 的那一點(diǎn)。對(duì)其他工藝（如：發(fā)酵，提取，純化等）可能需

31、要具體問(wèn)題具體對(duì)待。表 1 給出了原料藥的起始物料從哪一點(diǎn)引入工藝v1.0可編輯可修改processes ., ferme ntati on, extracti on, purificati on), this rati on ale should be established on a case-by-case basis. Table 1 gives guida nee on the point at which the API starti ngmaterial isno rmally in troduced into the process.From this point on, ap

32、propriate GMP as defi ned in this guida nee should be applied to these in termediatean d/or APImanu facturi ng steps. This would in clude the validationof critical process stepsdeterm ined to impact the quality of theAPI. However, it should be no ted that the fact that a compa ny chooses to validate

33、 a process step does not necessarily define that steps as critical.The guidaneein thisdocument wouldnormally be applied to the steps shown in gray in Table 1. However, all steps shown may not be completed. The stri ngency of GMPn API manu facturi ngshould in creaseas the process proceeds from early

34、API steps to final steps, purification, and packag ing. Physical process ing of APIs,過(guò)程的指導(dǎo)原則。從這步開(kāi)始，本指南中的有關(guān) GMP規(guī)范應(yīng)當(dāng) 應(yīng)用在這些中間體和/或原料藥的制造中。 這 包括對(duì)原料藥質(zhì)量有影響的關(guān)鍵工藝步驟的 驗(yàn)證。但是，值得注意的是廠商選擇某一步 驟進(jìn)行驗(yàn)證，并不一定將該步驟定為關(guān)鍵步 驟。本文件的指南通常適用于表 1中的灰色步驟。 但在表中體現(xiàn)的所有步驟并不是將應(yīng)用GMP管理的所有步驟全部體現(xiàn)出來(lái)了。原料藥生 產(chǎn)中的GMP要求應(yīng)當(dāng)隨著工藝的進(jìn)行，從原 料藥的前幾步到最后幾步，精制和包裝，

35、越 來(lái)越嚴(yán)格。原料藥的物理加工，如制粒、包 衣或顆粒度的物理處理 （例如制粉、微粉化） 應(yīng)當(dāng)按本指南的標(biāo)準(zhǔn)進(jìn)行。1212v1.0可編輯可修改such as granulation,coating or physicalmanipulationof particle size ., milling,micronizing) should becon ductedaccord ing to this guida nee.1313This GMPguidanee does not apply to steps 本GMP旨南不適用于引入定義了的“原料藥prior to the introduction

36、of the defined 的起始物料”以前的步驟。API starting material.Table 1: Application of this Guidance to API ManufacturingType ofManufacturingApplication of this guidance to steps (shown in gray) used in this type of manufacturingChemical manufacturingProduction of theAPI StartingmaterialIntroduction of theAPI sta

37、rting materialinto processProduction ofIntermediate(s)Isolation andpurificationPhysical processing, and packagingAPI derived fromCollection ofCutting, mixing,Introduction of theIsolation andPhysical processing, andanimal sourcesorgan, fluid, orand/or initialAPI starting materialpurificationpackaging

38、tissueprocessinginto processAPI extracted fromCollection of plantCutting and initialIntroduction of theIsolation andPhysical processing, andplant sourcesextraction(s)API starting materialpurificationpackaginginto processHerbal extractsCollection ofCutting and initialFurtherPhysical processing, andus

39、ed as APIplantsextracti onextractionpackagingAPI consisting ofCollection ofCutting/comminutingPhysical processing, andcomminuted orplants and/orpackagingpowdered herbscultivation andharvestingv1.0可編輯可修改Biotechnology:Establishment ofMaintenance ofCell culture and/orIsolation andPhysical processing, a

40、ndfermentation/cellmaster cell bank andworking cell bankfermentationpurificationpackagingcultureworking cell bank“Classical ”Establishment ofMaintenance of theIntroduction of theIsolation andPhysical processing, andfermentation tocell bankcell bankcells intopurificationpackagingproduce an APIferment

41、ation表1:本指南在原料藥生產(chǎn)中的應(yīng)用生產(chǎn)類(lèi)型本指南在用于各類(lèi)生產(chǎn)的工藝步驟（灰色背景）中的應(yīng)用化學(xué)品的生產(chǎn)原料藥起始物料的生產(chǎn)原料藥起始物料引入工藝過(guò)程中間體的生產(chǎn)分離和純化物理加工和包裝動(dòng)物源原料藥器官、分泌物或組織切割、混合和/或初步加原料藥起始物料引入工分離和純化物理加工和包裝的收集工藝過(guò)程從植物源提取的原料植物的收集切割和初步提取原料藥起始物料引入工分離和純化物理加工和包裝藥藝過(guò)程草藥提取物用作原料植物的收集切割和初步提取進(jìn)一步提取物理加工和包裝藥由粉碎的或粉末狀草植物的收集和/或培切割/粉碎物理加工和包裝藥組成的原料藥養(yǎng)和收獲生物技術(shù)：發(fā)酵/細(xì)胞主細(xì)胞庫(kù)和工作細(xì)胞工作細(xì)胞庫(kù)的維

42、護(hù)細(xì)胞培養(yǎng)和/或發(fā)酵分離和純化物理加工和包裝培養(yǎng)庫(kù)的建立“經(jīng)典”發(fā)酵生產(chǎn)細(xì)胞庫(kù)的建立細(xì)胞庫(kù)的維護(hù)細(xì)胞引入發(fā)酵分離和純化物理加工和包裝原料藥GMP的要求增加1414v1.0可編輯可修改2. QUALITY MANAGEMENTPrin ciplesQuality should be the resp on sibilities of all persons involved in manufacturing.Eachmanu facturershould establish,document, and implementan effectivesystem for managing qualit

43、y that involves the active participati on of man ageme nt and appropriatemanu facturi ng pers onn el.The system for man agi ng quality should en compass the orga ni zati onal structure, procedures, process and resources, as well as activities to en sure con fide nee that the API will meet itsintende

44、dspecifications for quality and purity.All quality-related activities should be defi ned and docume nted.There should be a quality un it(s) thatis independent of production and that fulfills both quality assuranee (QA and quality con trol (QC)resp on sibilities.2. 質(zhì)量管理總則參與原料藥生產(chǎn)的每一個(gè)人都應(yīng)當(dāng)對(duì)質(zhì)量 負(fù)責(zé)。每一個(gè)生產(chǎn)商都

45、應(yīng)當(dāng)建立并執(zhí)行一套有管 理人員和有關(guān)員工積極參與的有效的質(zhì)量管 理體系，并使其文件化。質(zhì)量管理體系應(yīng)當(dāng)包括組織機(jī)構(gòu)、規(guī)程、工藝和資源，以及確保原料藥會(huì)符合其預(yù)期的 質(zhì)量與純度要求所必需的活動(dòng)。所有涉及質(zhì) 量管理的活動(dòng)都應(yīng)當(dāng)明確規(guī)定，并使其文件 化。應(yīng)當(dāng)設(shè)立一個(gè)獨(dú)立于生產(chǎn)部門(mén)的質(zhì)量部門(mén)，同時(shí)履行質(zhì)量保證 (QA和質(zhì)量控制(QC的 職責(zé)。依照組織機(jī)構(gòu)的大小，可以是分開(kāi)的 QA和 QC部門(mén)，或者只是一個(gè)人或小組。1515v1.0可編輯可修改The quality unit can be in the form of separate QA and QC unitsor a singlein divi

46、dual or group, depe nding upon the size and structure of the orga ni zati on.Thepers onsauthorized to release應(yīng)當(dāng)指定授權(quán)發(fā)放中間體和原料藥的人員。in termediatesand APIs should be1616specified.All quality-related activities should所有有關(guān)質(zhì)量的活動(dòng)應(yīng)當(dāng)在其執(zhí)行時(shí)就記be recordedat the time theyare 錄。performed.Any deviati onfrom establish

47、ed任何偏離既定規(guī)程的情況都應(yīng)當(dāng)有文字記procedures shouldbe docume nted and錄并加以解釋。對(duì)于關(guān)鍵性偏差應(yīng)當(dāng)進(jìn)行調(diào)expla in ed.Criticaldeviatio nsshould be 查，并記錄調(diào)查經(jīng)過(guò)及其結(jié)果。in vestigated, and the in vestigati on and its con clusi ons should be docume nted.No materials should be released or used before the satisfactory completion of evaluati o

48、n by the quality un it(s) uni ess there are appropriate systems in place toallow forsuch use ., releaseunderquara nti neas describedin Section10 orthe use ofraw materialsor in termediates在質(zhì)量部門(mén)對(duì)物料完成滿(mǎn)意的評(píng)價(jià)之前， 何物料都不應(yīng)當(dāng)發(fā)放或使用，除非有合適的 系統(tǒng)允許此類(lèi)使用（如條款所述的待檢情況 下的使用，或是原料或中間體在等待評(píng)價(jià)結(jié) 束時(shí)的使用）。v1.0可編輯可修改pending completi

49、on of evaluati on).1717Procedures should exist for no tify ingresponsiblemanagement in a timely mannerof regulatory in spect ions, serious GMPdeficie ncies,productdefectsandrelatedactions.,quality-related應(yīng)當(dāng)有規(guī)程能確保公司的責(zé)任管理部門(mén)能及時(shí)得到有關(guān)藥政檢查、嚴(yán)重的GMP缺陷、產(chǎn)品缺陷及其相關(guān)活動(dòng) （如質(zhì)量投訴，召回, 藥政活動(dòng)等）的通知。compla in ts,recalls, and

50、regulatoryactio ns).Resp on sibilitiesof the Quality Unit(s)質(zhì)量部門(mén)的責(zé)任The quality un it(s) should be in volved in all quality-related matters.The quality un it(s) should review and approve all appropriate quality-related docume nts.質(zhì)量部門(mén)應(yīng)當(dāng)參與所有與質(zhì)量有關(guān)的事物。所有與質(zhì)量有關(guān)的文件應(yīng)當(dāng)由質(zhì)量部門(mén)審 核批準(zhǔn)。The mainresp on sibilitiesof

51、theindependent quality unit(s) should not be delegated. These resp on sibilitiesshouldbe described in writi ng and should in clude, but not n ecessarily be limited to:1. Releas ingor rejecti ng all APIs.Releas ing or rejecti ng in termediates獨(dú)立的質(zhì)量部門(mén)的主要職責(zé)不應(yīng)當(dāng)委派給他人。這些責(zé)任應(yīng)當(dāng)以文字形式加以說(shuō)明，而且應(yīng)當(dāng)包括，但不限于：1. 所有原料藥的

52、放行與否。用于生產(chǎn)商控制范圍以外的中間體的放行與否；2. 建立一個(gè)放行與拒收原材料、中間體、包裝材料和標(biāo)簽的系統(tǒng);v1.0可編輯可修改for use outside the con trol of themanu facturi ng compa ny2. Establish ing a system to release or reject raw materials, in termediates, packag ing, and labeli ng materials3. Review ing completed batch product ionand laboratorycontro

53、lrecords ofcritical process steps before release of the API for distribution4. Making sure that critical deviati onsare in vestigated and resolved5. Approvi ngallspecificatio nsandmaster product ion in struct ions6. Approvi ngall proceduresaffect ingthe quality of in termediates or APIs7. Making sure that internal audits (self- in spect ions) are performed8. Approvi ngin termediate and APIcon tract manufacturers9. Approvingchanges that potentiallyaffect in termediate or API qual