【正文】 e. API starting materials normally have defined chemical properties and structure.但是卻包括以血或血漿為原材料生產(chǎn)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。 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 not covered by this guidance, but should be performed in accordance with GMP guidances for drug (medicinal) products as defined by local authorities. Within the world munity, 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 this guidance.注冊(cè)/歸檔的所有承諾必須做到。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 agency to establish specific registration/filing requirements regarding APIs within the context of marketing/manufacturing authorizations or drug applications. All mitments in registration/filing documents should be met.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。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。 1. 簡介 Objective1. INTRODUCTION 實(shí)驗(yàn)室控制 Documentation 生產(chǎn) Validation 質(zhì)量 Equipment and Facilities設(shè)備和設(shè)施 Control of Raw Materials 原料的控制 Production19. APIs for Use in Clinical Trials 用于臨床研究的原料藥 General 收取、分離和精制 Viral Removal/Inactivation steps 投訴和召回的處理 Handling of Returns 穩(wěn)定性 Transfer of Information 信息的傳達(dá) Handling of Complaints and Recalls17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS 投訴與召回 重新加工 Recovery of Materials and Solvents 返工 Reworking 工藝驗(yàn)證的程序 Periodic Review of Validated Systems 驗(yàn)證文件 Qualification 驗(yàn)證方針 Validation Documentation12. VALIDATION11. LABORATORY CONTROLS 標(biāo)簽發(fā)放與控制 Packaging and Labeling Operations 包裝和貼簽操作 總則 Packaging Materials 包裝材料 Label Issuance and Control原料藥和中間體的包裝和貼簽 General 控制通則 Receipt and Quarantine 實(shí)驗(yàn)室控制記錄 Batch Production Record Review生產(chǎn)工藝規(guī)程（主生產(chǎn)和控制記錄） Batch Production Records (Batch Production and Control Records) 設(shè)備的清潔和使用記錄 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials4. BUILDINGS AND FACILITIESTable of Contents中英文） 目的 Regulatory Applicability法規(guī)的適用性 Scope2. QUALITY MANAGEMENT 總則 Responsibilities of the Quality Unit(s) 生產(chǎn)作業(yè)的職責(zé) Internal Audits (Self Inspection) 內(nèi)部審計(jì)（自檢） Product Quality Review3. PERSONNEL 人員的資質(zhì) Personnel Hygiene 水 Containment 限制 Lighting 排污和垃圾 Sanitation and Maintenance 衛(wèi)生和保養(yǎng) 設(shè)計(jì)和結(jié)構(gòu) Equipment Maintenance and Cleaning6. DOCUMENTATION AND RECORDS 文件和記錄 Documentation System and Specifications 文件系統(tǒng)和質(zhì)量標(biāo)準(zhǔn) Equipment cleaning and Use Record 批生產(chǎn)記錄審核 物料管理 General Controls 接收和待驗(yàn) Sampling and Testing of Ining Production Materials 進(jìn)廠物料的取樣與測試 Storage 儲(chǔ)存 Reevaluation8. PRODUCTION AND INPROCESS CONTROLS 工序取樣和控制 Blending Batches of Intermediates or APIs9. PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES 有效期和復(fù)驗(yàn)期 Reserve/Retention Samples 清洗驗(yàn)證 Validation of Analytical Methods 分析方法的驗(yàn)證14. REJECTION AND REUSE OF Rejection 拒收 Reprocessing 退貨 適用性 Traceability of Distributed APIs and Intermediates已分發(fā)的原料藥和中間體的可追溯性 Quality Management 質(zhì)量管理 Repackaging, Relabeling, and Holding of APIs and Intermediates原料藥和中間體的重新包裝、重新貼簽和待檢 Stability18. Specific Guidance for APIs Manufactured by Cell Culture/Fermentation用細(xì)胞繁殖/發(fā)酵生產(chǎn)的原料藥的特殊指南 General 變更 Laboratory Controls 術(shù)語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，“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)量保證水平的供選物來替代。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 manufacturer and are governed by national laws.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。 Regulatory Applicability當(dāng)某種物料在其制造或用于藥品的地區(qū)或國家被稱為原料藥，就應(yīng)該按照本指南進(jìn)行生產(chǎn)。它適用于無菌原料藥在滅菌前的步驟。This guidance covers APIs that are manufactured by chemical synthesis, extraction, cell culture/fermentation, recovery from natural sources, or any bination of these processes. Specific guidance for APIs manufactured by cell culture/fermentation is described in Section 、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。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 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 addition, the guidance does not apply to medical gases, bulkpackaged drug (medicinal) products (., tablets or capsules in bulk containers), or radiopharmaceuticals.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。原料藥的起始物料可能是在市場上有售、能夠通過合同或商業(yè)協(xié)議從一個(gè)或多個(gè)供應(yīng)商處購得，或由生產(chǎn)廠家自制。The pany should designate and document the rationale for the point at which production of the API begins. For synthetic processes, this is known as the point at which API starting materials are entered into the process. For other processes (., fermentation, extraction, purification), this rationale should be established on a casebycase basis. Table 1 gives guidance on the point at which the API starting material is normally introduced into the process.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)。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)出來了。