【正文】 g, approving, and distributing the instructions for the production of intermediates or APIs according to written procedures2. Producing APIs and, when appropriate, intermediates according to preapproved instructions3. Reviewing all production batch records and ensuring that these are pleted and signed4. Making sure that all production deviations are reported and evaluated and that critical deviations are investigated and the conclusions are recorded5. Making sure that production facilities are clean and, when appropriate, disinfected6. Making sure that the necessary calibrations are performed and records kept7. Making sure that the premises and equipment are maintained and records kept8. Making sure that validation protocols and reports are reviewed and approved9. Evaluating proposed changes in product, process or equipment10. Making sure that new and, when appropriate, modified facilities and equipment are qualified生產(chǎn)作業(yè)的職責應當以文字形式加以說明，并應當包括，但不限于以下內(nèi)容：1. 按書面程序起草、審核、批準和分發(fā)中間體或原料藥的生產(chǎn)指令；2. 按照已批準的指令生產(chǎn)原料藥或者中間體；3. 審核所有的批生產(chǎn)記錄確保其完整并有簽名；4. 確保所有的生產(chǎn)偏差都已報告、評價，對關鍵的偏差已做了調(diào)查，并記錄結論；5. 確保生產(chǎn)設施的清潔，必要時要消毒；6. 確保進行必要的校驗，并有記錄；7. 確保對廠房和設備進行保養(yǎng)，并有記錄；8. 確保驗證方案和報告的審核與批準；9. 對產(chǎn)品、工藝或設備擬作的變更進行評估；10. 確保新的或已改進的生產(chǎn)設施和設備經(jīng)過了確認。這些責任應當以文字形式加以說明，而且應當包括，但不限于：1. 所有原料藥的放行與否。 The quality unit(s) should review and approve all appropriate qualityrelated documents. 所有與質量有關的文件應當由質量部門審核批準。 Procedures should exist for notifying responsible management in a timely manner of regulatory inspections, serious GMP deficiencies, product defects and related actions (., qualityrelated plaints, recalls, and regulatory actions). 應當有規(guī)程能確保公司的責任管理部門能及時得到有關藥政檢查、嚴重的GMP缺陷、產(chǎn)品缺陷及其相關活動（如質量投訴，召回，藥政活動等）的通知。對于關鍵性偏差應當進行調(diào)查，并記錄調(diào)查經(jīng)過及其結果。 All qualityrelated activities should be recorded at the time they are performed. 所有有關質量的活動應當在其執(zhí)行時就記錄。依照組織機構的大小，可以是分開的QA和QC部門，或者只是一個人或小組。所有涉及質量管理的活動都應當明確規(guī)定，并使其文件化。 Each manufacturer should establish, document, and implement an effective system for managing quality that involves the active participation of management and appropriate manufacturing personnel. 每一個生產(chǎn)商都應當建立并執(zhí)行一套有管理人員和有關員工積極參與的有效的質量管理體系，并使其文件化。This GMP guidance does not apply to steps prior to the introduction of the defined API starting material.本GMP指南不適用于引入定義了的“原料藥的起始物料”以前的步驟。原料藥生產(chǎn)中的GMP要求應當隨著工藝的進行，從原料藥的前幾步到最后幾步，精制和包裝，越來越嚴格。The guidance in this document would normally be applied to the steps shown in gray in Table 1. However, all steps shown may not be pleted. The stringency of GMP in API manufacturing should increase as the process proceeds from early API steps to final steps, purification, and packaging. Physical processing of APIs, such as granulation, coating or physical manipulation of particle size (., milling, micronizing) should be conducted according to this guidance.本文件的指南通常適用于表1中的灰色步驟。這包括對原料藥質量有影響的關鍵工藝步驟的驗證。表1給出了原料藥的起始物料從哪一點引入工藝過程的指導原則。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。原料藥的起始物料一般來說有特定的化學特性和結構。An API starting material is a raw material, an intermediate, 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 merce, a material purchased from one or more suppliers under contract or mercial agreement, or produced inhouse. API starting materials normally have defined chemical properties and structure.“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，或者以主要結構單元的形式被結合進原料藥結構中。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)。但是卻包括以血或血漿為原材料生產(chǎn)的原料藥。通過細胞培養(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，應當符合地方當局所規(guī)定的藥品（醫(yī)療用品）生產(chǎn)的GMP指南。 ScopeThis 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.本文件適用于人用藥品（醫(yī)療用品）所含原料藥的生產(chǎn)。 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。本指南不影響負責藥政審理部門在原料藥上市/制造授權或藥品申請方面建立特定注冊/歸檔要求的能力。這方面的管理是生產(chǎn)者固有的責任，也是國家法律規(guī)定的。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。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、質量控制、放行、原料藥的儲存和分發(fā)及其相關控制的所有操作。Q7a（中英文對照）FDA原料藥GMP指南Table of Contents目錄1. INTRODUCTION1. 簡介 Objective Regulatory Applicability Scope2. QUALITY MANAGEMENT Principles Responsibilities of the Quality Unit(s) Responsibility for Production Activities Internal Audits (Self Inspection)（自檢） Product Quality Review3. PERSONNEL3. 人員 Personnel Qualifications Personnel Hygiene 人員衛(wèi)生 Consultants 顧問4. BUILDINGS AND FACILITIES4. 建筑和設施 Design and Construction 設計和結構 Utilities 公用設施 Water 水 Containment 限制 Lighting 照明 Sewage and Refuse 排污和垃圾 Sanitation and Maintenance 衛(wèi)生和保養(yǎng)5. PROCESS EQUIPMENT5. 工藝設備 Design and Construction 設計和結構 Equipment Maintenance and Cleaning 設備保養(yǎng)和清潔 Calibration 校驗 Computerized S