Technical Requirements for the Registration Dossier of EDMF/COS/CTD and Filing strategies in EU countries  EDMF/COS/CTD 注册文件的技术要求及在欧盟国家的文件编撰策略Filing strategies CEP ASMF/EDMF procedure ??? 文件编撰策略CEP ASMF/EDMF 程序??? ARED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com ARED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com Preparation and Filing of EDMF/ASMF for COS/CEP application ies  申请COS/CEP 的EDMF/ASMF 文件制作Certification procedure Application at the EDQM (European Directorate for the Quality of Medicines) How to apply ? Application form Procedere Timetable COS 证明程序在EDQM 申请（药品质量欧洲理事会）怎样申请？申请表程序时间表ARED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com ARED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com Content of the dossier for chemical purity and microbiological quality  文件内容化学纯度和微生物质量Schematic description 图解ALFRED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com ALFRED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com Application form –Request for New Certificate of Suitability  申请表－－ 新适应性证书的要求Certification procedure Application at the EDQM (European Directorate for the Quality of Medicines) How to apply ? Application form Procedere Timetable 证明程序申请EDQM (European Directorate for the Quality of Medicines) 如何申请? 申请表程序时间表ALFRED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com ALFRED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com Technical Advice to Applicants and Holders of Certificates of Suitability (CEP) 对适应性证书(CEP) 的申请者和持有者的技术建议 ALFRED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com ALFRED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com Procedure for Revision / Renewals of Certificates of Suitability (CEP) 适应性证书(CEP) 的修订/更新程序ALFRED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com ALFRED E. TIEFENBACHER(GmbH & Co)Van-der-Smissen-Str. 122767 HamburgGermanyTel.:	+49-40-441809-0Fax.:	+49-40-441809-26Mail.: info@tiefenbacher.comwww.tiefenbacher.com GMP (ICH Q7A) Compliance and Inspection for COS/CEPGMP for Active Pharmaceutical Ingredients (APIs)ICH Q7A, Annex 18 to EU Guide to GMP Dr. Berthold Stemmle Pharma Consulting Associated Partner of Concept Heidelberg GMP (ICH Q7A) 遵守COS/CEP 检查原料药的GMP (APIs)ICH Q7A, 欧盟GMP 指南附件18  Dr. Berthold Stemmle Pharma Consulting Associated Partner of Concept Heidelberg General The guideline was published by the EMEA (European Agency for Evaluation of Medicinal Products). Pharmaceutical manufacturers should only use APIs manufactured according to GMP in the manufacture of medicinal products. Not mandatory in the EU but when there are causes for concern, or when required by certain Member States, GMP inspections of API manufacturers will be carried out. An application for a centralised authorisation will trigger an inspection by inspectors of the competent authorities in the EU. Requirements laid down in the guideline should be fulfilled. 总则该指南由EMEA (European Agency for Evaluation of Medicinal Products) 出版发行药物制造商应当在医药产品的制造中仅使用那些按照GMP 生产的原料药欧盟没有命令要求，但当某个成员国表示关注或有要求时，将会对原料药的工厂开展GMP 检查一项关于集中授权的申请将会引发由欧盟内由资质的专家构成的检查员的检查。在下面指南中规定的要求应当履行Table of Contents Introduction Quality Management Personnel Buildings and Facilities Process Equipment Documentation and Records Materials Management Production and In-Process Controls Packaging and Identification Labelling of APIs and Intermediates Storage and Distribution Laboratory Controls Validation Change Control Rejection and Reuse of Materials 目录介绍质量管理人员建筑和设施工艺设备文件和记录物料管理生产和过程控制包装和原料药以及中间体的标签识别仓储和分销实验室控制验证变更控制不合格和物料的再使用Table of Contents Complaints and Recalls Contract Manufacturers (including Laboratories) Agents, Brokers, Traders, Distributers, Repackers, and Relabellers Specific Guidance for APIs manufactured by Cell Culture/Fermentation APIs for Use in Clinical Trials Glossary 目录投诉和召回合同制造商代理商，经纪人，贸易商，分销商，重新包装人，和重新贴签人由细胞培养/发酵制造的原料药的专门指南用于临床试验的原料药词汇表1. Introduction 1.1 Objective Provide GMP guidance for APIs under an appropriate system for managing quality. Help to ensure APIs quality and purity. Manufacturing“includes all operations of receipt of materials, Production, packaging, repackaging, relabelling, quality control, release, storage and distribution of APIs and the related controls. Should“indicates recommendations that are expected to apply unless shown to be inapplicable.... Does not cover safety aspects or environmental aspects. Does not define registration/filing requirements or modify pharmacopeial requirements 1. 介绍1.1 目的为原料药在适当的系统下进行质量管理，提供GMP 指导帮助保证原料药的质量和纯度制造－包括接受物料，生产，包装，重新包装，重新贴签，质量控制，放行，仓储和原料药的分销以及相关的控制等所有的操作“应当”指希望被应用的推荐措施，除非该措施证明是不适用的不涉及安全方面或环保方面不定义注册/文件要求或修正药典的要求1. Introduction 1.2 Regulatory Applicability When a material is classified in a region or country as API, manufactured there or used in a drug product, GMP requirements according to the guide have to be followed . 1.3 Scope The guide applies to the manufacture of APIs for use in human drug products. APIs manufactured by chemical sysnthesis, extraction, cell culture/fermentation, recovery from natural sources. API Starting Material“is a raw material, intermediate, or an API that is incorporated as a significant structural fragment into the structure of the API manufactured; defined chemical properties and structure! 1. 介绍1.2 药政适应性当一种物料被一个地区或国家列为原料药，在该地区制造或在某种药物产品中使用，必须根据本指南遵循GMP 要求。1.3 范围本指南应用于由化学合成，提取，细胞培养/发酵，自然原料提取的原料药制造。原料药起始物料是原料，中间体，或一种原料药，它具有所要生产的原料药的有效结构部分；明确的化学属性和结构Application of the Guide to API Manufacturing Chemical synthesis: production of API starting material- introduction of API starting material into process –production of intermediate(s) –isolation and purification- physical processing and packaging Derived from animal sources: collection of organ, fluid, or tissue –cutting, mixing, initial processing –introduction of the API starting material into process –isolation....... Extracted from plant sources: collection of plants –cutting and initial extraction –further extraction –physical processing API consisting of comminuted or powdered herbs: collection –cutting/comminuting –physical processing and packaging Biotechnology-Fermentation/cell culture: establishment of master and working cell bank –maintenance of working cell bank –cell