【正文】 PHARMACEUTICAL INSPECTION CONVENTION PHARMACEUTICAL INSPECTION COOPERATION SCHEME藥品檢驗公約藥品檢驗合作計劃GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS PART I藥用產(chǎn)品良好生產(chǎn)規(guī)范指南第一部分目錄第一章 質(zhì)量管理 2第二章人員 11第三章 廠房設施 17第四章 文件 25第五章 生產(chǎn) 41第六章質(zhì)量控制 53第七章 委托生產(chǎn)與委托檢驗 62第八章 產(chǎn)品投訴和召回 66第九章 自檢 69CHAPTER 1 第一章 質(zhì)量管理QUALITY MANAGEMENTPRINCIPLE 原則The holder of a manufacturing authorisation must manufacture medicinal products so as to ensure that they are fit for their intended use, ply with the requirements of the Marketing Authorisation and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and mitment by staff in many different departments and at all levels within the pany, by the pany’s suppliers and by the distributors. To achieve the quality objective reliably there must be a prehensively designed and correctly implemented system of Quality Assurance Incorporating Good Manufacturing Practice, and thus Quality Control and Quality Risk Management. It should be fully documented and its effectiveness monitored. All parts of the Quality Assurance systems should be adequately resourced with petent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the holder of the manufacturing authorisation and for the authorised person(s). 生產(chǎn)許可證持有人必須生產(chǎn)藥品，從而確保藥品適合預期用途、符合相應的上市許可證或臨床試驗許 可證要求，不因為安全性問題、質(zhì)量問題或有效性問題而把患者置于風險之中。實現(xiàn)上述質(zhì)量目標是公司高級管理人員的職責，并要求公司的供應商、銷售商，公司內(nèi)所有各級員工與許多不同部門的員工共同參與、一起努力。要可靠地實現(xiàn)這一質(zhì)量目標，必須綜 合設計一個整合藥品生產(chǎn)質(zhì)量管理規(guī)范（GMP）和質(zhì)量控制、質(zhì)量風險管理的制藥質(zhì)量保證體系并正確實施。質(zhì)量體系應當全面文件化，并監(jiān)察其有效性。整個制藥質(zhì)量體 系應當配備充足的具有資質(zhì)的人員，以及充分并適用的建筑物、設備和設施。生產(chǎn)許可證持有人以及質(zhì)量受權人有額外的法律責任。The basic concepts of Quality Assurance, Good Manufacturing Practice, Quality Control and Quality Risk Management are interrelated. They are described here in order to emphasise their relationships and their fundamental importance to the production and control of medicinal products.質(zhì)量保證、藥品生產(chǎn)質(zhì)量管理規(guī)范、質(zhì)量控制以及質(zhì)量風險管理的基本概念是相互關聯(lián)的。在這里對其進行描述是為了強調(diào)它們之間的聯(lián)系以及其對藥品生產(chǎn)和控制的重要性。QUALITY ASSURANCE質(zhì)量保證 Quality Assurance is a wideranging concept, which covers all matters, which individually or collectively influence the quality of a product. It is the sum total of the organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use. Quality Assurance therefore incorporates Good Manufacturing Practice plus other factors outside the scope of this Guide.質(zhì)量保證是一個寬泛的概念，涵蓋所有因素，這些因素單獨或共同影響產(chǎn)品質(zhì)量。質(zhì)量保證是為了保證藥品質(zhì)量符合預期用途，而進行的有組織的安排的總和。因此，質(zhì)量保證中包含著藥品生產(chǎn)質(zhì)量管理規(guī)范以及本指南的范圍內(nèi)的其他因素。The system of Quality Assurance appropriate for the manufacture of medicinal products should ensure that: 一個適當?shù)馁|(zhì)量保證體系應當確保：i. medicinal products are designed and developed in a way that takes account of the requirements of Good Manufacturing Practice 。藥品的設計和開發(fā)應考慮藥品生產(chǎn)質(zhì)量管理規(guī)范的要求；ii. production and control operations are clearly specified and Good Manufacturing Practice adopted。對生產(chǎn)和控制操作進行明確規(guī)定，并符合藥品生產(chǎn)質(zhì)量管理規(guī)范的要求；iii. managerial responsibilities are clearly specified。明確規(guī)定管理職責；iv. arrangements are made for the manufacture, supply and use of the correct starting and packaging materials。 對下述活動均有協(xié)議約束：生產(chǎn)、供應、使用正確的起始物料與包裝材料。v. all necessary controls on intermediate products, and any other inprocess controls and validations are carried out。對中間產(chǎn)品以及其他任何中間過程控制與驗證實施所有必要的控制；vi. the finished product is correctly processed and checked, according to the defined procedures。成品根據(jù)確定的程序進行正確生產(chǎn)和檢測；vii. medicinal products are not sold or supplied before an authorised person has certified that each production batch has been produced and controlled in accordance with the requirements of the marketing authorisation and any other regulations relevant to the production, control and release of medicinal products。質(zhì)量受權人需簽發(fā)證明以確認每一批次藥品的生產(chǎn)和控制均符合上市許可要求以及與藥品生產(chǎn) 、控制和放行相關的任何其他法規(guī)要求，未經(jīng)質(zhì)量受權人簽發(fā)證明的藥品不得銷售或供貨；viii. satisfactory arrangements exist to ensure, as far as possible, that the medicinal products are stored, distributed and subsequently handled so that quality is maintained throughout their shelf life。藥品貯存 、發(fā)運和后續(xù)處理確保有滿意的管理規(guī)程，從而盡量保證藥品貨架期內(nèi)的質(zhì)量ix. there is a procedure for selfinspection and/or quality audit, which regularly appraises the effectiveness and applicability of the quality assurance system.有自檢和 / 或質(zhì)量審計規(guī)程，以定期評價質(zhì)量保證體系的有效性與適用性。GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS (GMP)藥品生產(chǎn)質(zhì)量管理規(guī)范 Good Manufacturing Practice is that part of Quality Assurance which ensures that Medicinal products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorisation or product specification. Good Manufacturing Practice is concerned with both production and quality control. The basic requirements of GMP are that:藥品生產(chǎn)質(zhì)量管理規(guī)范是質(zhì)量管理體系的一部分，保證按適合預期用途的質(zhì)量標準及上市許可、臨床試驗許可或產(chǎn)品質(zhì)量標準要求始終如一地生產(chǎn)及控制產(chǎn)品。藥品生產(chǎn)質(zhì)量管理規(guī)范涉及生產(chǎn)和質(zhì)量控制。藥品生產(chǎn)質(zhì)量管理規(guī)范的基本要求是：i. all manufacturing processes are clearly defined, systematically reviewed in the light of experience and shown to be capable of consistently manufacturing medicinal products of the required quality and plying with their specifications。所有生產(chǎn)工藝得到明確規(guī)定、按照經(jīng)驗經(jīng)過系統(tǒng)的審核，并經(jīng)過證明表明有能力始終如一地生產(chǎn)具有所需質(zhì)量且符合質(zhì)量標準的藥品ii. critical steps of manufacturing processes and significant changes to the process are validated。生產(chǎn)工藝的關鍵步驟以及重大的工藝變更已經(jīng)驗證；iii. all necessary facilities for GMP are provided including:提供了 GM P需要的所有設施，包 括 ：a. appropriately qualified and trained personnel。 有適當資質(zhì)并經(jīng)過培訓的員工；b. adequate premises and space。 充足的廠房與空間 ；c. suitable equipment and services。 適 當 的 設 備 及 保 養(yǎng) ；d. correct materials, containers and labels。 恰當?shù)牟牧?、?器 和 標 簽 ；e. approved procedures and instructions。 經(jīng)批準的規(guī)程與操作方法；f. suitable storage and transport。 合 適 的 貯 存 與 運 輸 ；iv. instructions and procedures are written in an instructional form in clear and unambiguous language, specifically applic