【正文】 d, when appropriate, intermediates according to preapproved instructions3. The responsibility for production activities should be described in writing and should include, but not necessarily be limited to:1. 開展產(chǎn)品質(zhì)量審核（）。 確保有穩(wěn)定性數(shù)據(jù)支持中間體或原料藥的復(fù)驗期或有效期和儲存條件；15. 確保物料都經(jīng)過了適當(dāng)?shù)臋z驗并報告結(jié)果；14. 確保用有效的體系來維護(hù)和校驗關(guān)鍵設(shè)備；13. 確保調(diào)查并解決質(zhì)量問題的投訴；12. 審核并批準(zhǔn)驗證方案和報告；11. 批準(zhǔn)可能影響到中間體或原料藥質(zhì)量的變更；10. 確保進(jìn)行內(nèi)部審計（自檢）；8. 批準(zhǔn)所有的規(guī)格標(biāo)準(zhǔn)和主生產(chǎn)指令；6. 在供銷售的原料藥放行前，審核已完成的關(guān)鍵步驟的批生產(chǎn)記錄和實驗室檢驗記錄；4.用于生產(chǎn)商控制范圍以外的中間體的放行與否；2.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：1. Performing product quality reviews (as defined in Section ) Making sure that there is stability data to support retest or expiry dates and storage conditions on APIs and/or intermediates, where appropriate15. Making sure that materials are appropriately tested and the results are reported14. Making sure that effective systems are used for maintaining and calibrating critical equipment13. Making sure that qualityrelated plaints are investigated and resolved12. Reviewing and approving validation protocols and reports11. Approving changes that potentially affect intermediate or API quality10. Making sure that internal audits (selfinspections) are performed8. Approving all specifications and master production instructions6. Reviewing pleted batch production and laboratory control records of critical process steps before release of the API for distribution4. Releasing or rejecting all APIs. Releasing or rejecting intermediates for use outside the control of the manufacturing pany2. 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(dāng)由質(zhì)量部門審核批準(zhǔn)。 The quality unit(s) should be involved in all qualityrelated matters. 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(yīng)當(dāng)有規(guī)程能確保公司的責(zé)任管理部門能及時得到有關(guān)藥政檢查、嚴(yán)重的GMP缺陷、產(chǎn)品缺陷及其相關(guān)活動（如質(zhì)量投訴，召回，藥政活動等）的通知。 No materials should be released or used before the satisfactory pletion of evaluation by the quality unit(s) unless there are appropriate systems in place to allow for such use (., release under quarantine as described in Section 10 or the use of raw materials or intermediates pending pletion of evaluation). Any deviation from established procedures should be documented and explained. Critical deviations should be investigated, and the investigation and its conclusions should be documented. 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。 應(yīng)當(dāng)指定授權(quán)發(fā)放中間體和原料藥的人員。 The persons authorized to release intermediates and APIs should be specified. 應(yīng)當(dāng)設(shè)立一個獨(dú)立于生產(chǎn)部門的質(zhì)量部門，同時履行質(zhì)量保證(QA)和質(zhì)量控制 (QC)的職責(zé)。 There should be a quality unit(s) that is independent of production and that fulfills both quality assurance (QA) and quality control (QC) responsibilities. The quality unit can be in the form of separate QA and QC units or a single individual or group, depending upon the size and structure of the organization.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，以及確保原料藥會符合其預(yù)期的質(zhì)量與純度要求所必需的活動。每一個生產(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。參與原料藥生產(chǎn)的每一個人都應(yīng)當(dāng)對質(zhì)量負(fù)責(zé)。 2．質(zhì)量管理 PrinciplesThis 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(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。本文件的指南通常適用于表1中的灰色步驟。但是，值得注意的是廠商選擇某一步驟進(jìn)行驗證，并不一定將該步驟定為關(guān)鍵步驟。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。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。對于合成工藝而言，就是“原料藥的起始物料”進(jìn)入工藝的那一點(diǎn)。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)?！霸纤幍钠鹗嘉锪稀笔侵敢环N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。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.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(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。本文件適用于人用藥品（醫(yī)療用品）所含原料藥的生產(chǎn)。 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. Scope在世界范圍內(nèi)對原料藥的法定定義是各不相同的。 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/歸檔的所有承諾必須做到。本指南未規(guī)定注冊/歸檔的要求、或修改藥典的要求。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。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 guida