【正文】 ualityrelated returns, plaints and recalls● A review of adequacy of corrective actions 原料藥的定期質(zhì)量審核應(yīng)當以證實工藝的一致性為目的來進行。 The quality unit(s) should review and approve all appropriate qualityrelated documents. 所有與質(zhì)量有關(guān)的文件應(yīng)當由質(zhì)量部門審核批準。依照組織機構(gòu)的大小，可以是分開的QA和QC部門，或者只是一個人或小組。原料藥生產(chǎn)中的GMP要求應(yīng)當隨著工藝的進行，從原料藥的前幾步到最后幾步，精制和包裝，越來越嚴格。對于合成工藝而言，就是“原料藥的起始物料”進入工藝的那一點。但是卻包括以血或血漿為原材料生產(chǎn)的原料藥。 Regulatory ApplicabilityWithin 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.在世界范圍內(nèi)對原料藥的法定定義是各不相同的。In this guidance, the term manufacturing is defined to include all operations of receipt of materials, production, packaging, repackaging, labeling, relabeling, quality control, release, storage and distribution of APIs and the related controls. In this guidance, the term should identifies remendations that, when followed, will ensure pliance with CGMPs. An alternative approach may be used if such approach satisfies the requirements of the applicable statues. For the purposes of this guidance, the terms current good manufacturing practices and good manufacturing practices are equivalent.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、原料藥的儲存和分發(fā)及其相關(guān)控制的所有操作。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。它適用于無菌原料藥在滅菌前的步驟。 Section 19 contains guidance that only applies to the manufacture of APIs used in the production of drug (medicinal) products specifically for clinical trials (investigational medicinal products).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，特別是臨床實驗用藥（研究用醫(yī)療產(chǎn)品）的原料藥制造。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 of the API. However, it should be noted that the fact that a pany chooses to validate a process step does not necessarily define that steps as critical.從這步開始，本指南中的有關(guān)GMP規(guī)范應(yīng)當應(yīng)用在這些中間體和/或原料藥的制造中。Table 1: Application of this Guidance to API ManufacturingType of ManufacturingApplication of this guidance to steps (shown in gray) used in this type of manufacturingChemical manufacturingProduction of the API Starting materialIntroduction of the API starting material into processProduction of Intermediate(s)Isolation and purificationPhysical processing, and packagingAPI derived from animal sourcesCollection of organ, fluid, or tissueCutting, mixing, and/or initial processingIntroduction of the API starting material into processIsolation and purificationPhysical processing, and packagingAPI extracted from plant sourcesCollection of plantCutting and initial extraction(s)Introduction of the API starting material into processIsolation and purificationPhysical processing, and packagingHerbal extracts used as APICollection of plantsCutting and initial extractionFurther extractionPhysical processing, and packagingAPI consisting of minuted or powdered herbsCollection of plants and/or cultivation and harvestingCutting/minutingPhysical processing, and packagingBiotechnology: fermentation/cell cultureEstablishment of master cell bank and working cell bankMaintenance of working cell bankCell culture and/or fermentationIsolation and purificationPhysical processing, and packaging“Classical” fermentation to produce an APIEstablishment of cell bankMaintenance of the cell bankIntroduction of the cells into fermentationIsolation and purificationPhysical processing, and packagingIncreasing GMP requirements表 1: 本指南在原料藥生產(chǎn)中的應(yīng)用生產(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/細胞培養(yǎng)主細胞庫和工作細胞庫的建立工作細胞庫的維護細胞培養(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)原料藥細胞庫的建立細胞庫的維護細胞引入發(fā)酵分離和純化物理加工和包裝