1、,A Brief Introduction to API & Drug Product Application to US and EU欧美API&制剂注册,GMP管理部培训教材,Purpose & Benefits of Application to the US & EU医药企业欧美注册的目的及作用 Authorities responsible for the API & Drug Product Application in US & EU欧美医药注册机构Application to FDA FDA注册申请Application to EDQM EDQM注册申请Application
2、to EMEA & Competent National Authorities in the EU EMEA欧盟药政国家注册Comparison of Application to the US & EU欧美注册比较总结 Acronyms缩写,A Brief Introduction to API & Drug Product Application to US and EU欧美API&制剂注册,Purpose: market APIs & Drug Products in US & EU 目的：为进驻欧美市场Benefits作用 ：Increasing the opportunity to
3、 enter other international markets可提高进入其它国际市场的机会An indication about product quality & level of company management是产品质量和企业管理水平的重要标志Building up the company status in the international market企业树立国际市场形象的基本和重要的条件a strong support for sales in the national market企业运作国内市场的强有力支持中国医药出口结构发生改变 changing the expo
4、rt of the chinese pharm. 国内药企进入国际市场情况,The Purpose & Benefits of Application to US&EU医药企业欧美注册的目的及作用,Purpose & Benefits of Application to the US & EU医药企业欧美注册的目的及作用 Authorities responsible for the API & Drug Product Application in US & EU 欧美医药注册机构Application to FDAFDA注册申请Application to EDQM EDQM注册申请App
5、lication to EMEA & Competent National Authorities in the EU EMEA 欧盟药政国家注册Comparison of Application to the US & EU欧美注册比较总结 Acronyms缩写,Brief Introduction to API & Drug Product Application to US and EU欧美API&制剂注册,1 US美国: FDA ( responsible for both API & Drug Product)FDA （制剂、API） 2. EU欧盟: EDQM ( responsi
6、ble for API & Excipients) EDQM （原料药和辅料) EMEA ( responsible for both API & Drug Product) EMEA （原料药和制剂） Competent National Authorities of the EU Countries欧盟内的药政国家,Authorities Responsible for API & Drug Product Application in US & EU欧美医药注册机构,Purpose & Benefits of Application to the US & EU医药企业欧美注册的目的及作
7、用 Authorities responsible for the API & Drug Product Application in US & EU 欧美医药注册机构Application to FDA FDA注册申请Application to EDQM EDQM注册申请Application to EMEA & Competent National Authorities in the EU EMEA 欧盟药政国家注册Comparison of Application to the US & EU欧美注册比较总结 Acronyms 缩写,Brief Introduction to API
8、 & Drug Product Application to US and EU欧美API&制剂注册,Application to FDA - Procedure FDA注册流程,Application of Human Use Drug Product to FDA includes IND, NDA & ANDA FDA制剂的注册分为IND、NDA、ANDAIf applicants want to sell a newly developed innovating drug product in the US, then they should submit an IND to FDA
9、in order to carry out clinical trial in US 一种市场上没有同效力的药品研发出来以后，若要进入美国市场，需向FDA提交IND，申请在美国进行临床试验The applicant of the innovator drug product which has successfully passes IND process should submit an NDA to the FDA in order to market the innovator drug product in US 通过临床试验的新药要进入美国市场，需向FDA提交NDA，申请在美国销售T
10、he applicant of generic drug product which is bioequivalent to the innovating drug product in strength, quality, intended use, etc. should submit an ANDA to FDA in order to sell the generic drug product in US 当一种新药的专利保护期过了以后，同类型的仿制药就可以生产了，若仿制药要进入美国，需向FDA提交ANDA，申请在美国销售。,Application to FDA - Drug Prod
11、uct 制剂注册,Application to FDA - IND 临床申请注册流程,Application to FDA - NDA 新药申请注册流程,Application to FDA - ANDA 简略新药申请流程,Purpose & Benefits of Application to the US & EU医药企业欧美注册的目的及作用 Authorities responsible for the API & Drug Product Application in US & EU欧美医药注册机构Application to FDA FDA注册申请Application to EDQ
12、M EDQM注册申请Application to EMEA & Competent National Authorities in the EU EMEA 欧盟药政国家注册Comparison of Application to the US & EU欧美注册比较总结 Acronyms 缩写,Brief Introduction to API & Drug Product Application to US and EU 欧美API&制剂注册,For APIs which are included in European Pharmacopoeia, the manufacturer can
13、apply to EDQM to obtain COS certificate欧洲药典中存在的APIs可以向EDQM提交COS/CEP证书申请，分为6步：1.Applicant submits COS Dossier to EDQMAPIs厂家向EDQM提交COS/CEP申请文件 2. EDQM reviews the dossier for completeness and sends an acknowledgement letter EDQM within 8 days of receipt收到资料的8天内进行资料完整性的核实，并向药厂确认材料的接收3.Secretariat of ED
14、QM appoints Rapporteur and Co-rapporteur to review the dossier EDQM认证秘书处指定专家对资料进行审核4.Site Inspection, if necessary如有需要，进行现场检查 5.If Approved, EDQM grants COS/CEP若通过，则EDQM颁发COS/CEP证书 6. COS/CEP is valid for 5 years and can be renewed 6 month prior to the deadline COS证书有效期5年，期满前6个月，提交更新材料或者没有更新的申明。,App
15、lication to EDQM EDQM API注册,Application to EDQM EDQM API注册,Purpose & Benefits of Application to the US & EU医药企业欧美注册的目的及作用 Authorities responsible for the API & Drug Product Application in US & EU欧美医药注册机构Application to FDA FDA注册申请Application to EDQM EDQM注册申请Application to EMEA & Competent National Au
16、thorities in the EU EMEA 欧盟药政国家注册Comparison of Application to the US & EU欧美注册比较总结 Acronyms 缩写,Brief Introduction to API & Drug Product Application to US and EU 欧美API&制剂注册,For the manufacturers who manufacture APIs which are not included in European Pharmacopoeia or has no COS, they can submit EDMF/A
17、SMF to EMEA or Competent National Authorities. EDMF/ASMF can be divided into 2 parts: AP & RP. AP is about non-confidential information, while RP is about confidential information.对于欧洲药典中不存在的或者没有申请COS/CEP的原料药的厂商，可以向EMEA或者欧盟药政国家提交ASMF。ASMF主要分为两个部分：公开部分和保密部分。公开部分主要为申请原料药的基本信息，保密部分主要为产品配方及工艺等的描述。The su
18、bmission process of ASMF ASMF的递交程序 ：,Application to EMEA & Competent National Authorities 欧盟EMEA和药政国家 - API,Application to EMEA & Competent National Authorities 欧盟EMEA和药政国家 - API,ASMF的递交程序 ：,Centralized Procedure、Decentralized Procedure、Independent National Procedure, Mutual Recognition Procedure， e
19、tc. 对于制剂在欧盟的上市申请根据药物分类和目标市场的不同，申请流程可分为集中申请流程、非集中申请流程、单独国家申请流程、相互承认申请流程：A marketing authorization granted under the centralized procedure is valid for the entire Community market, which means the medicinal product may be put on the market in all Member States. 通过集中式申请获得的上市许可证对整个欧盟市场都有效，即该药在所有的欧盟国家都可上
20、市销售The decentralized procedure is to be used in order to obtain marketing authorizations in several Member States where the medicinal product in question has not yet received a marketing authorization in any Member State at the time of application. 当被申请药品还没有取得任何一个欧盟国家上市许可，但是又不属于可通过集中式申请范围内的情况下，若要在多个
21、欧盟国家上市，需采取非集中申请方式,Application to EMEA & Competent National Authorities - Drug Product 欧盟EMEA和药政国家 - 制剂,Independent national procedures will continue, but are strictly limited from 1 January 1998 to the initial phase of mutual recognition (granting of the marketing authorization by the Reference Memb
22、er State) and to medicinal products which are not to be authorized in more than one Member State. 单独国家申请流程还被继续使用，但从1998年1月1日起，使用被严格限制，并只作为相互承认申请流程的初始步骤，并且只局限于还没有取得任何欧盟成员国上市许可证的药品。The mutual recognition procedure is to be used in order to obtain marketing authorizations in several Member States where
23、 the medicinal product in question has received a marketing authorization in any Member State at the time of application. 当被申请药品已取得任何一个欧盟国家上市许可证的情况下，若要取得其他成员国的上市许可证，需采取互认申请方式。,Application to EMEA & Competent National Authorities - Drug Product 欧盟EMEA和药政国家 - 制剂,Application to EMEA & Competent Nationa
24、l Authorities - Centralized 欧盟EMEA和药政国家 - 集中式申请,The Centralized procedure is divided in 7 steps:集中式申请流程：,1. An application submitted to EMEA 制剂药厂向EMEA提交上市许可申请2. CHMP evaluates the scientific information CHMP对申请资料的科学性方面进行评估3. Inspection requested by CHMP 如果CHMP有要求，则对药厂进行现场检查4. European Commission dra
25、fts decision欧洲委员会根据CHMP的评估和现场检查的结果起草最终结论5. Consulting with member states in Standing Committee在欧盟常务委员会咨询成员国意见6. EC adopts decision & grants marketing authorization 欧洲委员会得出最终结论，并颁发上市许可证7. Marketing authorization is valid for 5 years and can be renewed 6 month prior deadline上市许可证有效期5年，有效期到前6个月，提出续签申请,
26、Application to EMEA & Competent National Authorities - Decentralized欧盟EMEA和药政国家 - 非集中式申请,The decentralized procedure is divided in five steps:非集中申请流程：Validation step 所有申请国家接收到申请后，都需要对资料的完整性进行确认Assessment step I 审核步骤1：由主负责成员国审核，并起草报告等Assessment step II 审核步骤2：其它相关成员国通过Discussion at the coordination gr
27、oup level, if needed 如果有需要，则成员国之间相互协调National Marketing Authorization step 颁发上市许可证,Application to EMEA & Competent National Authorities - Independent National欧盟EMEA和药政国家 - 单独成员国申请,The Independent National procedure is divided into four steps:单独成员国申请流程：1. Application to the specific competent member
28、state 向某个特定的欧盟国家提出上市许可申请2. Validation step 申请国家接收到申请后，对资料的完整性进行确认3. Assessment step 审核步骤：对申请文件进行审核4. National Marketing Authorization step 颁发上市许可证,Application to EMEA & Competent National Authorities - Mutual Recognition欧盟EMEA和药政国家 - 互认申请,The mutual recognition procedure is divided in six steps:互认申请
29、流程：National validation by the reference Member State 由已颁发上市许可证的国家审核2. Preparation or update of assessment report by reference Member State (90 days) 由已颁发上市许可证的国家准备或者更新评估报告（90天内）3. Validation by the concerned Member States 由其他相关国家审核4. Approval by the concerned Member States (90 days) 其他相关国家同意批准5. Dis
30、cussion at the coordination group level, if needed 如果有需要，则成员国之间相互协调6. National Marketing Authorization step 其他相关国家颁发上市许可证,Brief Introduction to API & Drug Product Application to US and EU欧美API&制剂注册,Purpose & Benefits of Application to the US & EU医药企业欧美注册的目的及作用 Authorities responsible for the API & D
31、rug Product Application in US & EU欧美医药注册机构Application to FDA FDA注册申请Application to EDQM EDQM注册申请Application to EMEA & Competent National Authorities in the EU EMEA欧盟药政国家注册Comparison of Application to the US & EU欧美注册比较总结 Acronyms缩写,Comparison of application to US & EU欧美注册比较总结,1. Authorities: US- FDA
32、only; EU- EMEA, EDQM, Competent National Authorities 管理机构：美国是一个国家，只有一个FDA管理医药注册；欧盟由多个独立的成员国组成，所以有EMEA、EDQM等联合药监机构，而每个成员国也可能有自己单独的药监局。2. API: US- DMF to FDA; EU- COS Dossier to EDQM (if included in EP), or ASMF to EMEA API：美国API注册是向FDA提交DMF；欧盟则是可以向EDQM提交COS申请（如果药物已被记录在药典中），也可向EMEA提交ASMF。3. Drug Produ
33、ct: US- Submitted to FDA, marketed in US market; EU- submitted to EMEA or a competent national authority or several competent national authorities, marketed respectively in EU market or a EU member state or several EU member states. 制剂：美国制剂注册是向FDA提交申请，成功后可以在全美上市；欧盟则按照药物的分类，向EMEA或者一个成员国或者多个成员国提交申请，成功
34、后，可以相应地在所有欧盟国家或者某个成员国或者多个成员国上市。,Brief Introduction to API & Drug Product Application to US and EU欧美API&制剂注册,Purpose & Benefits of Application to the US & EU医药企业欧美注册的目的及作用 Authorities responsible for the API & Drug Product Application in US & EU欧美医药注册机构Application to FDA FDA注册申请Application to EDQM ED
35、QM注册申请Application to EMEA & Competent National Authorities in the EU EMEA欧盟药政国家注册Comparison of Application to the US & EU欧美注册比较总结 Acronyms缩写,缩写 Acronym,ANDA: Abbreviated New Drug Application 简略新药申请/仿制药申请ASMF(EDMF): Active Substance Master Files 原料药主文件CDER: Center for Drug Evaluation & Research药物评估研究
36、中心CHMP: the Committee for Medicinal Products for Human Use 人用药委员会COS: Certificate of Suitability To Monographs of the European Pharmacopoeia 欧洲药典实用性证书DMF: Drug Master Files 药物主文件EDQM: European Directorate for the Quality of MedicinesEMEA: European Medicines AgencyFDA: U.S. Food & Drug AdministrationIND: Investigational New Drug Application 新药临床试验申请NDA: New Drug Application 新药申请OGD: Office of Generic Drug 仿制药办公室,谢谢！,
