【正文】 the quality part of the dossier ? Classification of active substances : 1. New active substances used for the first time in a medicinal product 2. Existing active substances not described in the European Pharmacopoeia 3. Existing active substances described in the European Pharmacopoeia CEP 程序?qū)? DMF 程序 ? 針對(duì)文件質(zhì)量部分中活性物質(zhì)要求的概述的指南 ? 活性物質(zhì)的分類 : 1. 在藥品中第一次使用的新的活性成分 2. 在歐洲藥典中沒(méi)有描述的現(xiàn)有的活性物質(zhì) 3. 在歐洲藥典中有描述的現(xiàn)有的活性物質(zhì) Application for a marketing authorisation of a Medicinal Product requires information on the Active Substance (AS): 1. Certificate of suitability to the Monograph of the European Monograph 2. Active Substance Master File (ASMF ) procedure 3. Full details of manufacture 藥品市場(chǎng)許可申請(qǐng) 活性物質(zhì) (AS)的要求信息 : 1. 針對(duì)歐洲藥典專論的適應(yīng)性證書(shū) 2. 活性物質(zhì)主文件 (ASMF ) 程序 3. 完整的制造細(xì)節(jié) Feasible ways to submit Depending on the classification of the AS 1. For new active substances and substances not described in the . : ASMF/EDMF 2. For existing substances, descrribed in the . : CEP or ASMF/EDMF The AS manufacturer provides either: ? No 1) CEP or ? No 2 the ASMF/EDMF (Applicants part be included in the MA) 可行的遞交方式 取決于活性物質(zhì)的分類 1. 對(duì)于在歐洲藥典中沒(méi)有描述的物質(zhì)和新的活性物質(zhì) : ASMF/EDMF 2. 對(duì)于在歐洲藥典中描述的現(xiàn)有的活性物質(zhì) : CEP 或 ASMF/EDMF AS 制造商提供下列兩者中的一個(gè) : ? 第 1， CEP或 ? 第 2， ASMF/EDMF (MA包括此申請(qǐng)部分 ) Submission of the CEP Generally avoiding any subsequent reassessment AS manufacturer submits : ? copy of the most curent CEP ? Written asurance that no significant changes in the manufacturing method have taken place Applicant submits : ? Results of batch analysis demonstrating pliance with the . Monograph CEP的遞交 通常應(yīng)避免下列任何的重新評(píng)估 作為制造商遞交 : ? 最新的 CEP的復(fù)印件 ? 書(shū)面保證：在采用的制造方法中沒(méi)有發(fā)生重大變更 申請(qǐng)人遞交 : ? 批分析結(jié)果要證明符合歐洲藥典專論的要求 ASMF/EDMF procedure Guideline on Active Substance Master File procedure : ? CPMP/QWP/227/02 ? Terms European Drug Master File (EDMF) and Active Substance Master File (ASMF) are interchangable ? Overview EDMF content ? Template letter of access and covering letter ASMF/EDMF程序 活性物質(zhì)主文件程序的指南 : ? CPMP/QWP/227/02 ?歐洲藥物主文件 (EDMF)和活性物質(zhì)主文件 (ASMF)的條款可以通用 ? EDMF內(nèi)容概覽 ?準(zhǔn)閱信和封面信的模板 ASMF/EDMF procedure ? Overall content of the ASMF/EDMF as indicated in NTA/CTD format Module 3 ? AP contains information noncondidental ? RP contains remaining information such as : ? Detailed information on the manufacturing steps (reaction conditions, temperature etc.) ? Evaluation of critical steps ? Quality control during manufacture ? Validation ASMF/EDMF程序 ? 按照 NTA/CTD格式模塊 3的指示做 ASMF/EDMF的全部?jī)?nèi)容 ? AP包含非保密的信息 ? RP包含剩余的如下信息 : ? 制造步驟的詳細(xì)信息 (反應(yīng)條件，溫度，等等 ) ? 關(guān)鍵步驟的評(píng)估 ? 制造中的質(zhì)量控制 ? 驗(yàn)證 ASMF/EDMF Submission EDMF can only be submitted in support of an MAA EDMF Holder should submit to the MA holder: ? Copy of the latest version of the AP ? Copy of the QOS ? Letter of access AP contains information noncondidental EDMF Holder should submit to the authorities ? Complete EDMF with covering letter ? Letter of access ASMF/EDMF遞交 EDMF只能在 MAA的支持下遞交 EDMF的持有者遞交到 MA的持有者 : ? AP的最近版本的復(fù)印件 ? QOS的復(fù)印件 ? EDMF持有者應(yīng)當(dāng)把 AP包含的非保密內(nèi)容的準(zhǔn)閱信遞交 到 官方部門 ? 有封面信的完整 EDMF ? 準(zhǔn)閱信 ARED E. TIEFENBACHER (GmbH amp。 Co) VanderSmissenStr. 1 22767 Hamburg Germany Tel.: +49404418090 Fax.: +494044180926 Mail.: ARED E. TIEFENBACHER (GmbH amp。 How to Apply ? 如何申請(qǐng)？ Submission ? Submission of one SINGLE copy of the full dossier ? QOS in addition to paper copy , electronic submission preferably in WORD format or readwrite pdf ? Samples of 12 representative mercial batches (about 10 g) ? Application format and Annex 1 – 5 遞交 ? 遞交整個(gè)文件的一份拷貝 ? QOS部分除了用文本文件，電子文本的遞交最好用 WORD文本或pdf ? 取 12批有代表性的商業(yè)批次的樣品 (約 10g) ? 申請(qǐng)格式和附件 15 Annexes ? Annex 1 Letter of Authorisation ( if applicable) ? Annex 2 Letter of agreement ( if manufacturer not CEP holder) ? Annex 3 Declaration that manufacture of the substance is according to the dossier and GMP rules ? Annex 4 Letter of declaration of willingness to be inspected ? Annex 5 Letter of declaration regarding the use of material of human or animal origin Annexes ? 附件一 授權(quán)信 (如果適用 ) ? 附件二協(xié)議書(shū) (如果制造商不是 CEP 的持有人 ) ? 附件三 所提交文件中的藥物是按照 GMP規(guī)則制造的 . ? 附件四 愿意接受檢查的聲明信 ? 附件五關(guān)于使用源于人或動(dòng)物材料的聲明信 Content of the Dossier Revised Guideline implemented by 1 September 2022 PA/PH/CEP (04) 1 3 R January 2022 : ? Quality Overall Summary QOS according to the Notice to Applicants Volume 2 B ? Summary of the content of the dossier ? Discussion about the ability of the EP monograph to control the quality of the drug , ? in particular the declared potential impurities,or the necessity for alternative methods ? Justification where testing for possible impurities are omitted ? Imp. not detected in any batches or not present due to a particular production 文件目錄 2022年九月一日生效的修訂版指南 PA/PH/CEP (04) 1 3 R January 2022 : ? 質(zhì)量綜述 申請(qǐng)人通知 卷 2B ? 文件內(nèi)容的概述 ? 討論關(guān)于用歐洲藥典專論的要求來(lái)控制藥物質(zhì)量的能力 ? 特別是藥典公布的潛在雜質(zhì) ,或替代方法的必要性 ? 省略對(duì)可能雜質(zhì)的檢測(cè)的理由 ? 在任何批次中不檢測(cè)的或由于某種特別的產(chǎn)物而不存在的雜質(zhì) Content of the Dossier General information 1 ? Commercialisation history of the substance : licensing history for medicinal products in Europe that contain the substance defined here ? Declarations : Annexes 15 ? Annex 3, applied GMP should ply the ICH Q7A , if available a copy of the GMP certificate ? If other parties are involved , details of their involvement , site addresses ? Manufacturer of the final substance performs purification only, declarations on GMP and willigness to be inspected should be provided for the contract manufacturer 文件目錄 一般信息 1 ? 物質(zhì)的商業(yè)化歷史 :在歐洲藥用產(chǎn)品的許可歷史包括這里定義的物質(zhì) ? 聲明 :附件 15