原料藥GMP指南(中英文對(duì)照)

1、精選文檔 Q7a （中英文對(duì)照 ） 目錄 FDA 原料藥 GMP 指南 Table of Contents 1. INTRODUCTION 1. 簡(jiǎn)介 1.1 Objective 1.1 目的 1.2 Regulatory Applicability 1.2 法規(guī)的適用性 1.3 Scope 1.3 范圍 2. QUALITY MANAGEMENT 2. 質(zhì)量管理 2.1 Principles 2.1 總則 2.2 Responsibilities of the Quality Unit(s) 2.2 質(zhì)量部門的責(zé)任 2.3 Responsibility for Production Acti

2、vities 2.3 生產(chǎn)作業(yè)的職責(zé) 2.4 Internal Audits (Self Inspection) 2.4 內(nèi)部審計(jì)（自檢） 2.5 Product Quality Review 2.5 產(chǎn)品質(zhì)量審核 3. PERSONNEL 3. 人員 3.1 Personnel Qualifications 3. 人員的資質(zhì) 3.2 Personnel Hygiene 3.2 人員衛(wèi)生 3.3 Consultants 3.3 顧問 4. BUILDINGS AND FACILITIES 4. 建筑和設(shè)施 4.1 Design and Construction 4.1 設(shè)計(jì)和結(jié)構(gòu) 4.2 Ut

3、ilities 4.2 公用設(shè)施 4.3 Water 4.3 水 4.4 Containment 4.4 限制 4.5 Lighting 4.5 照明 4.6 Sewage and Refuse 4.6 排污和垃圾 4.7 Sanitation and Maintenance 4.7 衛(wèi)生和保養(yǎng) 5. 工藝設(shè)備 5.1 設(shè)計(jì)和結(jié)構(gòu) 5.2 設(shè)備保養(yǎng)和清潔 5.3 校驗(yàn) 5. PROCESS EQUIPMENT 5.1 Design and Construction 5.2 Equipment Maintenance and Cleaning 5.3 Calibration 87 / 82 5.

4、4 Computerized Systems 5.4 計(jì)算機(jī)控制系統(tǒng) 6. DOCUMENTATION AND RECORDS 6.1 Documentation System and Specifications 6.2 Equipment cleaning and Use Record 6.3 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials 6.4 Master Production Instructions (Master Production and Control Record

5、s) 6.5 Batch Production Records (Batch Production and Control Records) 6.6 Laboratory Control Records 6.7 Batch Production Record Review 6. 文件和記錄 6.1 文件系統(tǒng)和質(zhì)量標(biāo)準(zhǔn) 6.2 設(shè)備的清潔和使用記錄 6.3 原料、中間體、原料藥的標(biāo)簽和包裝材 料的記錄 6.4 生產(chǎn)工藝規(guī)程（主生產(chǎn)和控制記錄） 6.5 批生產(chǎn)記錄（批生產(chǎn)和控制記錄） 6.6 實(shí)驗(yàn)室控制記錄 6.7 批生產(chǎn)記錄審核 7. MATERIALS MANAGEMENT 7. 物料管理 7

6、.1 General Controls 7.1 控制通則 7.2 Receipt and Quarantine 7.2 接收和待驗(yàn) 7.3 Sampling and Testing of Incoming 7.3 進(jìn)廠物料的取樣與測(cè)試 Production Materials 7.4 Storage 7.4 儲(chǔ)存 7.5 Re-evaluation 7.5 復(fù)驗(yàn) 8. 生產(chǎn)和過程控制 8. PRODUCTION CONTROLS AND IN-PROCESS 8.1 Production Operations 8.1 生產(chǎn)操作 8.2 Time Limits 8.2 時(shí)限 8.3 In-pro

7、cess Sampling and Controls 8.4 Blending Batches of Intermediates or 8.3 工序取樣和控制 8.4 中間體或原料藥的混批 8.5 污染控制 APIs 8.5 Contamination Control AND 9. 原料藥和中間體的包裝和貼簽 9. PACKAGING AND IDENTIFICATION LABELING OF APIs INTERMEDIATES 9.1 General 9.2 Packaging Materials 9.3 Label Issuance and Control 9.4 Packaging

8、and Labeling Operations 10. STORAGE AND DISTRIBUTION 10.1 Warehousing Procedures 10.2 Distribution Procedures 9.1 總則 9.2 包裝材料 9.3 標(biāo)簽發(fā)放與控制 9.4 包裝和貼簽操作 10. 儲(chǔ)存和分發(fā) 10.1 入庫(kù)程序 10.2 分發(fā)程序 11. 實(shí)驗(yàn)室控制 11.1 控制通則 11.2 中間體和原料藥的測(cè)試 11.3 分析方法的驗(yàn)證 11.4 分析報(bào)告單 11.5 原料藥的穩(wěn)定性監(jiān)測(cè) 11.6 有效期和復(fù)驗(yàn)期 11.7 留樣 13. 變更的控制 OF 14. 拒收和物料的再

9、利用 14.1 拒收 14.2 返工 14.3 重新加工 14.4 物料與溶劑的回收 14.5 退貨 15. 投訴與召回 16. CONTRACT MANUFACTURERS (INCLUDING LABORATORIES) 16. 協(xié)議生產(chǎn)商（包括實(shí)驗(yàn)室） 17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS 17.1 Applicability 17.2 Traceability of Distributed APIs and Intermediates 17.3 Quality Management

10、17.4 Repackaging, Relabeling, and Holding of APIs and Intermediates 17. 代理商、經(jīng)紀(jì)人、貿(mào)易商、經(jīng)銷商、重新 包裝者和重新貼簽者 17.1 適用性 17.2 已分發(fā)的原料藥和中間體的可追溯性 17.3 質(zhì)量管理 17.4 原料藥和中間體的重新包裝、重新貼簽 和待檢 11. LABORATORY CONTROLS 11.1 General Controls 11.2 Testing of Intermediates and APIs 11.3 Validation of Analytical Procedures 11.4

11、Certificates of Analysis 11.5 Stability Monitoring of APIs 11.6 Expiry and Retest Dating 11.7 Reserve/Retention Samples 12. VALIDATION 12. 驗(yàn)證 12.1 Validation Policy 12.1 驗(yàn)證方針 12.2 Validation Documentation 12.2 驗(yàn)證文件 12.3 Qualification 12.3 確認(rèn) 12.4 Approaches to Process Validation 12.4 工藝驗(yàn)證的方法 12.5 Pr

12、ocess Validation Program 12.5 工藝驗(yàn)證的程序 12.6 Periodic Review of Validated Systems 12.6 驗(yàn)證系統(tǒng)的定期審核 12.7 Cleaning Validation 12.7 清洗驗(yàn)證 12.8 Validation of Analytical Methods 12.8 分析方法的驗(yàn)證 13. CHANGE CONTROL 14. REJECTION AND RE-USE MATERIALS 14.1 Rejection 14.2 Reprocessing 14.3 Reworking 14.4 Recovery of

13、Materials and Solvents 14.5 Returns 15. COMPLAINTS AND RECALLS 17.5 Stability 17.5 穩(wěn)定性 17.6 Transfer of Information 17.6 信息的傳達(dá) 17.7 Handling of Complaints and Recalls 17.7 投訴和召回的處理 17.8 Handling of Returns 17.8 退貨的處理 18. Specific Guidance for APIs 18. 用細(xì)胞繁殖 / 發(fā)酵生產(chǎn)的原料藥的特殊 Manufactured by Cell Culture

14、/Fermentation 指南 18.1 General 18.1 總則 18.2 Cell Bank Maintenance and Record 18.2 細(xì)胞庫(kù)的維護(hù)和記錄的保存 Keeping 18.3 Cell Culture/Fermentation 18.3 細(xì)胞繁殖 / 發(fā)酵 18.4 Harvesting, Isolation and Purification 18.4 收取、分離和精制 18.5 Viral Removal/Inactivation steps 18.5 病毒的去除 / 滅活步驟 19. APIs for Use in Clinical Trials 19

15、. 用于臨床研究的原料藥 19.1 General 19.1 總則 19.2 Quality 19.2 質(zhì)量 19.3 Equipment and Facilities 19.3 設(shè)備和設(shè)施 19.4 Control of Raw Materials 19.4 原料的控制 19.5 Production 19.5 生產(chǎn) 19.6 Validation 19.6 驗(yàn)證 19.7 Changes 19.7 變更 19.8 Laboratory Controls 19.8 實(shí)驗(yàn)室控制 19.9 Documentation 19.9 文件 20. Glossary 20. 術(shù)語 Q7a GMP Gui

16、dance for APIs Q7a 原料藥的 GMP 指南 1. INTRODUCTION 1.1 Objective This document is intended to provide guidance regarding good manufacturing practice (GMP) for the manufacturing of active pharmaceutical ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensur

17、e that APIs meet the quality and purity characteristics that they purport, or are represented, to possess. In this guidance, the term manufacturing is defined to include all operations of receipt of materials, production, packaging, repackaging, labeling, relabeling, quality control, release, storag

18、e and distribution of APIs and the related controls. In this guidance, the term should identifies recommendations that, when followed, will ensure compliance with CGMPs. An alternative approach may be used if such approach satisfies the requirements of the applicable statues. For the purposes of thi

19、s guidance, the termscurrentgood manufacturing practicesandgood manufacturing practices are equivalent. 1. 簡(jiǎn)介 1.1 目的 本文件旨在為在合適的質(zhì)量管理體系下制造 活性藥用成分（以下稱原料藥）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。 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

20、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 平的供選物來替代。本指南中的“現(xiàn)行優(yōu)良 生產(chǎn)管理規(guī)范（ cGMP ）”和“優(yōu)良生產(chǎn)管理 規(guī)范（ GMP ）”是等同的。 The guidance as a whole does not cover safety aspects for the personnel engaged in manufacturing, nor aspects related to protecting the environment. These controls are inherent responsibilities of the man

21、ufacturer and are governed by national laws. 本指南在總體上未涉及生產(chǎn)人員的安全問 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 的。 This guidance is not intended to define registration and/or filing requirements or modify pharmacopoeial requirements. This guidance does not affect the ability of the responsible regulatory ag

22、ency to establish 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。 specific registration/filing requirements regarding APIs within the context of marketing/manufacturing authorizations or drug applications. All commitments in registration/filing docum

23、ents should be met. 1.2 Regulatory Applicability Within the world community, materials may vary as to their legal classification as an API. When a material is classified as an API in the region or country in which it is manufactured or used in a drug product, it should be manufactured according to t

24、his guidance. 1.3 Scope This guidance applies to the manufacture of APIs for use in human drug (medicinal) products. It applies to the manufacture of sterile APIs only up to the point immediately prior to the APIs being rendered sterile. The sterilization and aseptic processing of sterile APIs are n

25、ot covered by this guidance, but should be performed in accordance with GMP guidances for drug (medicinal) products as defined by local authorities. This guidance covers APIs that are manufactured by chemical synthesis, extraction, cell culture/fermentation, recovery from natural sources, or any com

26、bination of these processes. Specific guidance for APIs manufactured by cell culture/fermentation is described in Section 18. This guidance excludes all vaccines, whole cells, whole blood and plasma, blood and plasma derivatives (plasma fractionation), and gene therapy APIs. However, it does include

27、 APIs that are produced using blood or plasma as raw materials. Note that cell substrates (mammalian, plant, insect or microbial cells, tissue or animal sources including transgenic animals) and early process steps may be subject to GMP but are not covered by this guidance. In 1.2 法規(guī)的適用性 在世界范圍內(nèi)對(duì)原料藥的

28、法定定義是各不相 同的。當(dāng)某種物料在其制造或用于藥品的地 區(qū)或國(guó)家被稱為原料藥，就應(yīng)該按照本指南 進(jìn)行生產(chǎn)。 1.3 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)。它適用于無菌原料藥在滅菌前 的步驟。本指南不包括無菌原料藥的消毒和 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。 本文件適用于通過化學(xué)合成、提取、細(xì)胞培 養(yǎng)/發(fā)酵，通過從自然資源回收，或通過這些 工藝的結(jié)合而得到的原料藥。通過細(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

29、。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（例如，散裝的片劑和膠 囊）和放射性藥物的生產(chǎn)。 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。 addition, the guidance does not apply to medical gases, bulk-packaged drug (medicinal) prod

30、ucts (e.g., tablets or capsules in bulk containers), or radiopharmaceuticals. “原料藥的起始物料”是指一種原料、中間 體或原料藥，用來生產(chǎn)一種原料藥，或者以 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 始物料一般來說有特定的化學(xué)特性和結(jié)構(gòu)。 Section 19 contains guidance that only applies to the manufacture of APIs used in

31、the production of drug (medicinal) products specifically for clinical trials (investigational medicinal products). 生產(chǎn)廠商要指定并用書面文件說明原料藥的 生產(chǎn)從何處開始的理論依據(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）可能需要具體問題具體對(duì)待。表 1 給出了原料藥的起始物料從哪一點(diǎn)引入工藝 過程的指導(dǎo)原則。 An API starting material is a raw material, an intermed

32、iate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API starting material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or pro

33、duced in-house. API starting materials normally have defined chemical properties and structure. 從這步開始， 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。 The company should designate and document the rationale for the point at which production of th

34、e API begins. For synthetic processes, this is known as the point at which API starting materials are entered into the process. For other processes (e.g., fermentation, extraction, purification), this rationale should be established on a case-by-case basis. Table 1 gives guidance on the point at whi

35、ch the API starting material is normally introduced into the process. From this point on, appropriate GMP as defined in this guidance should be applied to these intermediate and/or API manufacturing steps. This would include the validation of critical process steps determined to impact the quality o

36、f the API. However, it should be noted that the fact that a company chooses to validate a process step does not necessarily define that steps as critical. This GMP guidanee does not apply to steps本GMP指南不適用于引入定義了的原料藥 prior to the introduction of the defined API 的起始物料”以前的步驟。 starting material. Type of

37、 Manufacturing Application of this guidance to steps (shown in gray) used in this type of manufacturing Chemical manufacturing Production of the API Starting material Introduction of the API starting material into process Production of Intermediate(s) Isolation and purification Physical processing,

38、and packaging API derived from Collection of organ, Cutting, mixing, and/or Introduction of the API Isolation and Physical processing, and animal sources fluid, or tissue initial processing starting material into purification packaging process API extracted from Collection of plant Cutting and initi

39、al Introduction of the API Isolation and Physical processing, and plant sources extraction(s) starting material into purification packaging process Herbal extracts used Collection of plants Cutting and initial Further Physical processing, and as API extracti on extraction packaging API consisting of

40、 Collection of plants Cutting/comminuting Physical processing, and comminuted or and/or cultivation packaging powdered herbs and harvesting Biotechnology: Establishment of Maintenance of working Cell culture and/or Isolation and Physical processing, and fermentation/cell master cell bank and cell ba

41、nk fermentation purification packaging culture working cell bank “ Classical ” Establishment of cell Maintenance of the cell Introduction of the cells Isolation and Physical processing, and fermentation to bank bank into fermentation purification packaging produce an API Table 1: Application of this

42、 Guidance to API Manufacturing In creas ing GMP requireme nts The guida nee in this docume nt would no rmally be applied to the steps show n in gray in Table 1. However, all steps shown may not be completed. The stringency of GMP in API manu facturi ng should in crease as the process proceeds from e

43、arly API steps to final steps, purificati on,and packagi ng. Physical process ing of APIs, such as granu lati on, coati ng or physical manipulation of particle size (e.g., milli ng,micronizing) should be con ducted accord ing to this guida nee. 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

44、來了。 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， 越來越嚴(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。 生產(chǎn)類型 本指南在用于各類生產(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 的收集 切割、混合和/或初步加 工 原料藥起始物料引入工 藝過程 分離和純化 物理加工和包裝 從植物源提取的原料 藥 植物的收集 切割和初步提取 原料藥起始物料引入工 藝過程 分離和純化

45、 物理加工和包裝 草藥提取物用作原料 藥 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 由粉碎的或粉末狀草 藥組成的原料藥 植物的收集和/或培養(yǎng) 和收獲 切割/粉碎 物理加工和包裝 生物技術(shù)：發(fā)酵/細(xì)胞 培養(yǎng) 主細(xì)胞庫(kù)和工作細(xì)胞 庫(kù)的建立 工作細(xì)胞庫(kù)的維護(hù) 細(xì)胞培養(yǎng)和/或發(fā)酵 分離和純化 物理加工和包裝 經(jīng)典”發(fā)酵生產(chǎn)原 料藥 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 表1:本指南在原料藥生產(chǎn)中的應(yīng)用 2. QUALITY MANAGEMENT 2.1 Prin ciples 2.10 Quality should be the resp on sibil

46、ities of all pers ons in volved in manu facturi ng. 2.11 Each manu facturer should establish, document, and implement an effective system for managing quality that involves the active participation of management and appropriate manu facturi ng pers onn el. 2.12 The system for managing quality should

47、 en compass theorga ni zatio nalstructure, procedures, process and resources, as well as activities to en sure con fide nee that the API will meet its inten ded specificati ons for quality and purity. All quality-related activities should be defi ned and docume nted. 2.13 There should be a quality u

48、nit(s) that is in depe ndent of product ion and that fulfills both quality assuranee (QA) and quality control (QC) resp on sibilities. The quality unit can be in 2. 質(zhì)量管理 2.1總則 2.10參與原料藥生產(chǎn)的每一個(gè)人都應(yīng)當(dāng)對(duì)質(zhì) 量負(fù)責(zé)。 2.11每一個(gè)生產(chǎn)商都應(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。 2.12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

49、 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。 2.13應(yīng)當(dāng)設(shè)立一個(gè)獨(dú)立于生產(chǎn)部門的質(zhì)量部 門，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 的QA和QC部門，或者只是一個(gè)人或小組。 the form of separate QA and QC units or a single individual or group, depending upon the size and structure of the organization. 2.14 The persons authorized to release

50、intermediates and APIs should be specified. 2.15 All quality-related activities should be recorded at the time they are performed. 2.16 Any deviation from established procedures should be documented and explained. Critical deviations should be investigated, and the investigation and its conclusions

51、should be documented. 2.17 No materials should be released or used before the satisfactory completion of evaluation by the quality unit(s) unless there are appropriate systems in place to allow for such use (e.g., release under quarantine as described in Section 10 or the use of raw materials or int

52、ermediates pending completion of evaluation). 2.18 Procedures should exist for notifying responsible management in a timely manner of regulatory inspections, serious GMP deficiencies, product defects and related actions (e.g., quality-related complaints, recalls, and regulatory actions). 2.2 Respons

53、ibilities of the Quality Unit(s) 2.20 The quality unit(s) should be involved in all quality-related matters. 2.21 The quality unit(s) should review and approve all appropriate quality-related documents. 2.22 The main responsibilities of the independent quality unit(s) should not be delegated. These

54、responsibilities should be described in writing and should include, but not 2.14 應(yīng)當(dāng)指定授權(quán)發(fā)放中間體和原料藥的人 員。 2.15 所有有關(guān)質(zhì)量的活動(dòng)應(yīng)當(dāng)在其執(zhí)行時(shí)就 記錄。 2.16 任何偏離既定規(guī)程的情況都應(yīng)當(dāng)有文字 記錄并加以解釋。對(duì)于關(guān)鍵性偏差應(yīng)當(dāng)進(jìn)行 調(diào)查，并記錄調(diào)查經(jīng)過及其結(jié)果。 2.17 在質(zhì)量部門對(duì)物料完成滿意的評(píng)價(jià)之 前，任何物料都不應(yīng)當(dāng)發(fā)放或使用，除非有 合適的系統(tǒng)允許此類使用 （如 10.20 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） 。 2.18 應(yīng)當(dāng)有規(guī)程

55、能確保公司的責(zé)任管理部門 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。 2.2 質(zhì)量部門的責(zé)任 2.20 質(zhì)量部門應(yīng)當(dāng)參與所有與質(zhì)量有關(guān)的事 物。 2.21 所有與質(zhì)量有關(guān)的文件應(yīng)當(dāng)由質(zhì)量部門 審核批準(zhǔn)。 2.22 獨(dú)立的質(zhì)量部門的主要職責(zé)不應(yīng)當(dāng)委派 給他人。這些責(zé)任應(yīng)當(dāng)以文字形式加以說明， 而且應(yīng)當(dāng)包括，但不限于： necessarily be limited to: 1. Releasing or rejecting all APIs. Releasing or rejecting intermediates for use

56、 outside the control of the manufacturing company 2. Establishing a system to release or reject raw materials, intermediates, packaging, and labeling materials 3. Reviewing completed batch production and laboratory control records of critical process steps before release of the API for distribution

57、4. Making sure that critical deviations are investigated and resolved 5. Approving all specifications and master production instructions 6. Approving all procedures affecting the quality of intermediates or APIs 7. Making sure that internal audits (self-inspections) are performed 8. Approving interm

58、ediate and API contract manufacturers 9. Approving changes that potentially affect intermediate or API quality 10. Reviewing and approving validation protocols and reports 11. Making sure that quality-related complaints are investigated and resolved 12. Making sure that effective systems are used fo

59、r maintaining and calibrating critical equipment 13. Making sure that materials are appropriately tested and the results are reported 14. Making sure that there is stability data to support retest or expiry dates and storage conditions on APIs and/or intermediates, where appropriate 15. Performing p

60、roduct quality reviews (as defined in Section 2.5) 2.3 Responsibility for Production Activities The responsibility for production activities should be described in writing and should include, but not necessarily be limited to: 1. 所有原料藥的放行與否。 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)；