1.   Introduction概述

This document provides guidance forelectronic submissions for Certificate of Suitability (CEPs) applicationssubmitted to the EDQM. Information and requirements described in this documentare intended to facilitate the handling and assessment of submissions for CEPsand to maintain their lifecycle even if the submission is not an eCTD.

本文件為提交給EDQM的CEP申請(qǐng)?zhí)峁╇娮由陥?bào)指南。在本文件中所描述的信息和需求意在便于CEP申報(bào)資料的處理和評(píng)審，以及其生命周期維護(hù)（即使申報(bào)資料并不是eCTD）。

2.  Scopeand general requirements范圍和一般要求

Thisguidance should be applied for all electronic submissions sent to EDQM in thecontext of applications for CEPs.

本指南適用于所有CEP申報(bào)過程中發(fā)送給EDQM的電子申報(bào)資料。

EDQM does not accept any paperapplications. All submissions should be in electronic format.

EDQM不接受任何紙質(zhì)申報(bào)資料。所有申報(bào)均應(yīng)為電子格式。

The following electronic submissionformats are accepted: PDF, NeeS, VNeeS and eCTD, but the acceptability of theformat depends on the type of submission as described in section 3.

以下電子申報(bào)格式可以接受：PDF、NeeS、VNeeS 和 eCTD，但不同申報(bào)類型的格式是否可接受以第3部分所述為準(zhǔn)。

Changingthe electronic format for a CEP application is possible at the start of aprocedure (e.g. when applying for a revision or renewal). This means movingfrom PDF to NeeS or eCTD, or from NeeS to eCTD. Coming back to a previoussubmission format is not allowed (e.g. sending a NeeS submission whenpreviously an eCTD submission was sent.)

在開始一個(gè)程序時(shí)可以改變CEP申報(bào)的電子格式（例如，在申請(qǐng)修訂或更新時(shí)）。這意味著從PDF轉(zhuǎn)為NeeS或eCTD，或從NeeS轉(zhuǎn)為eCTD。不允許退回之前的申報(bào)格式（例如，不能在之前提交了eCTD申報(bào)之后再以NeeS格式提交）。

3.  Electronicsubmission formats電子申報(bào)資料的格式

For new CEP applications,eCTD format is required (except for applications for the TSE risk and for substancesfor veterinary use only, see below).

新的CEP申報(bào)資料需要采用eCTD格式（除了TSE風(fēng)險(xiǎn)和僅供獸用申報(bào)以外，參見以下內(nèi)容）。

For revisions, renewals andnotifications, the following possible submission formats are accepted: eCTD orNeeS. Submissions in eCTD format are recommended by the EDQM.

修訂、更新和通知時(shí)，可以接受以下申報(bào)格式：eCTD和NeeS。EDQM建議采用eCTD格式提交申報(bào)資料。

The identification of the submissionformat type in the CEP application form is important.

CEP申報(bào)表格中申報(bào)格式類型的識(shí)別號(hào)很重要。

Electronic files should be inaccordance with specific Guidance for Industry on Providing RegulatoryInformation in Electronic Format (see the links in the sectionsbelow for each submissionformat).

電子文件應(yīng)符合具體的“以電子格式提交注冊(cè)信息行業(yè)指南”（參見以下部分鏈接中每種申報(bào)格式）。

Allfiles should be in PDF and the folder and file-naming convention of ICH M2 eCTDSpecification and EU Module 1 Specification should be applied. Other types of files arenot accepted (Word, JPEG, Excel,...), with the exception of the files requiredfor publishing an eCTD submission.

所有文件均應(yīng)為PDF格式，文件夾和文件命名應(yīng)遵守ICH M2 eCTD標(biāo)準(zhǔn)和EU模塊1標(biāo)準(zhǔn)。不接受其它類型的文件（Word、JPEG、Excel……），eCTD申報(bào)資料所需的發(fā)布文件除外。

The use of attached files in a pdffile is not allowed nor are pdf files with active javascripts (form fields,…)or containing watermarks.

不允許在PDF文件中使用附加文件，也不允許在PDF中使用激活的java腳本（表格域……）或放置水印。

CEP applications for theTSE risk TSE風(fēng)險(xiǎn)CEP申報(bào)

The eCTD or NeeS submission format isnot appropriate for CEP applications for the TSE risk, consequently, applicantsare invited to submit a single PDF for Module 3, and adapt the directorystructure/file naming as proposed in annex 1.

eCTD或NeeS申報(bào)格式不適合于TSE風(fēng)險(xiǎn)的CEP申報(bào)，因而，誠(chéng)請(qǐng)申報(bào)人為模塊3提交單一PDF文件，并采納附錄1所指的目錄結(jié)構(gòu)/文件命名。

CEP applications forsubstances for veterinary use only僅供獸用物質(zhì)的CEP申報(bào)

eCTD, NeeS (forrevisions/renewals) or VNeeS format may be used for such products (see guidanceavailable by the following linkhttp://esubmission.ema.europa.eu/tiges/vetesub.htm).

此類產(chǎn)品可以使用eCTD、NeeS（修訂/更新）或VNeeS格式（參見上述鏈接指南）。

3.1.       eCTD submission format電子申報(bào)資料格式

The eCTD structure should be inaccordance with the current versions of the related documents (specifications,guidance, etc.) available on the following websites:

eCTD結(jié)構(gòu)應(yīng)依據(jù)以下網(wǎng)頁(yè)中提供的相關(guān)文件的現(xiàn)行版本制訂：

-     http://esubmission.ema.europa.eu

-     http://estri.ich.org/eCTD/index.htm

It should be clarified that the eCTDCEP dossier remains, from a technical perspective, a  s t andalo n e dossier and is distinctfrom any marketing authorisation dossier and lifecycle.

要澄清的是eCTD格式的CEP文檔從技術(shù)角度來說仍然是一份獨(dú)立的文檔，與任何上市許可文檔和生命周期是區(qū)分開的。

Whensubmitting the first eCTD submission, an initial sequence 0000 should beprovided. When switching from another submission format to eCTD, it is stronglyrecommended to include any information already assessed and approved previouslyin a “baseline” sequence 0000 (refer to section 5). If files or sections of theeCTD contain a lot of information, additional bookmarks or “l(fā)evels of granularity”are recommended for facilitating the review (refer to annex 2). The use of bookmarks isallowed, especially when responding to an EDQM deficiency letter (responses toquestions and supportive data).

在提交首個(gè)eCTD申報(bào)資料時(shí)，應(yīng)使用初始序列號(hào)0000.如果是從其它申報(bào)格式轉(zhuǎn)換為eCTD，強(qiáng)烈建議在“基準(zhǔn)”序列0000（參見第5部分）中包括之前已審評(píng)和批準(zhǔn)的所有信息。如果eCTD文件或部分包括許多信息，建議制作更多的書簽或“層級(jí)”有便于審評(píng)（參見第2部分）。允許使用書簽，尤其是在回復(fù)EDQM缺陷信時(shí)（回復(fù)問題和支持性數(shù)據(jù)）。

Beforesubmitting an eCTD to EDQM, it should be technically validated using anappropriate checker/validation tool. If pass/fail errors are detected duringEDQM validation at receipt, the submission will be blocked or rejected.

在提交eCTD給EDQM之前，應(yīng)使用適當(dāng)?shù)臋z查工具/驗(yàn)證工具進(jìn)行技術(shù)驗(yàn)證。如果在EDQM接收驗(yàn)證中發(fā)現(xiàn)成功/失敗錯(cuò)誤，則申報(bào)資料會(huì)被打回或拒收。

Theoperation attributes chosen should be appropriate to allow the lifecycle of thesubmission (refer to section 5).

所選操作屬性應(yīng)適當(dāng)，以便于申報(bào)資料的生命周期管理（參見第5部分）。

Building the envelope andmodule 1:在模塊1中設(shè)定信封信息：

Accordingto the current EU Module 1 specification (3.0.1 and 3.0.2 in January 2018) theenvelope for a CEP application should be filled in as follows:

依據(jù)當(dāng)前EU模塊1的標(biāo)準(zhǔn)（2018年8月3.0.1和3.0.2），CEP申報(bào)的信封應(yīng)如下填寫：

For existing sequences based on oldDTD versions, the DTD version should ideally be changed at the start of a new regulatoryactivity.

如果有些序列下的申報(bào)還是基于舊的DTD版本，在開始新的注冊(cè)活動(dòng)時(shí)最好更改DTD版本。

Thecountry code “edqm” should be selected for the application form and otherdocuments in module 1, according to the current EU M1 Specification, availableon the following website:  http://esubmission.ema.europa.eu/eumodule1/index.htm

根據(jù)當(dāng)前的EU M1標(biāo)準(zhǔn)，在申報(bào)表和模塊1的其它文件中應(yīng)選擇國(guó)家代碼“edqm”。該標(biāo)準(zhǔn)在上述網(wǎng)址中可以下載。

3.2.       NeeS submission formatNeeS申報(bào)格式

The NeeS structure and specificationas well as the validation criteria should be in accordance with the guidanceand documents available on the following website:http://esubmission.ema.europa.eu/tiges/cmbdocumentation.html

NeeS結(jié)構(gòu)和標(biāo)準(zhǔn)及其驗(yàn)證標(biāo)準(zhǔn)應(yīng)符合相關(guān)指南，該指南文件在上述官網(wǎng)可下載。

The CTD file/directory structure andnaming shall be implemented with the addition of a Table of Content(s) asappropriate.

CTD文件/目錄結(jié)構(gòu)和命名在執(zhí)行時(shí)應(yīng)增加目錄表（適當(dāng)時(shí)）。

If files or sections of theNeeS contain a lot of information, additional levels of granularity are recommended forfacilitating the review (refer to annex 2).

如果NeeS文件或部分包括了大量的資料，建議增加分層以便于審評(píng)（參見附錄2）。

4.  Contentand structure of an application申報(bào)資料的內(nèi)容和結(jié)構(gòu)

Annexes 3 and 4 describe howto structure a CEP application in eCTD or NeeSsubmission formats.

附錄3和附錄4描述了eCTD和NeeS申報(bào)格式中的CEP資料結(jié)構(gòu)。

Annex 1 describesthe recommended file/directory structure for the pdf submission format, for TSEapplications only.

附錄1描述了針對(duì)僅TSE申報(bào)所建議的PDF申報(bào)格式文件/目錄結(jié)構(gòu)。

An application shouldcontain 3 modules as described below:

一份申報(bào)資料應(yīng)包括3個(gè)模塊，描述如下：

In Module 1:在模塊1中：

-        Coverletter

-        封面函

-         EDQMApplication Form including signed declarations (as relevant)

-         EDQM申報(bào)表，包括簽字聲明（如相關(guān)）

-         Informationabout the Expert, CV as relevant (for a new application)

-         專家資料、CV（如相關(guān)）（新申報(bào)）

-        Responses: when responding to anEDQM deficiency letter, applicants should include a document/file listing thequestions with the corresponding responses and supportive data.

-        回復(fù)：如果是回復(fù)給EDQM缺陷函，申報(bào)人應(yīng)包括一份文件列出問題及相應(yīng)回復(fù)和支持性數(shù)據(jù)。

-            Additionaldata: asection/folder which may contain if relevant a toxicological report, a signedcopy of a CEP, etc.

-        其它數(shù)據(jù)：某個(gè)部分/文件夾，其中可以包括相關(guān)毒性報(bào)告、一份簽字的CEP副本等

-        Revisions: a completed comparativetable (annex 7 to the application form) outlining the approved and proposedupdated text of module 3.

-        修訂：一份完整的對(duì)比表（申報(bào)表附錄7），列出模塊3中已批準(zhǔn)的和擬更新的內(nèi)容。

In Module 2 (new CEP applications):在模塊2中（新的CEP申報(bào)）：

-         QualityOverall Summary, prepared preferably using the EDQM template (the “Word” filetemplate should be converted into a pdf file).

-         質(zhì)量綜述，最好使用EDQM的模塊起草（要將WORD文件模板轉(zhuǎn)成PDF文件）。

In Module 3:在模塊3中

-         For a new CEP application: technical documentationstructured in accordance with the CTD as defined by ICH guidance documents.

-         新CEP申報(bào)：技術(shù)文件按ICH指南文件中指定的CTD結(jié)構(gòu)制作

-         Splittingthe data between an Applicant’s and a Restricted part is not encouraged for CEPapplications, but if these are submitted, the EMA “Practical guidelines on theuse of the eCTD format for ASMFs for Active Substance Master File Holders andMarketing Authorisation Holders” should be used as a basis; the CTD sectionsshould be clearly identified with the part they belong to.

-         不鼓勵(lì)將CEP申報(bào)資料拆分為保密部分和公開部分，但如果拆分提交，則應(yīng)采用EMA“ASMF持有人和上市許可持有人的ASMF使用eCTD格式實(shí)操指南”作為基礎(chǔ)。應(yīng)清楚定義每個(gè)CTD部分的歸屬。

-         Theuse of annexes/attachments is not allowed in Module 3.

-         在模塊3中不允許使用附錄/附件。

-         For a response to an EDQMdeficiency letter,or for a notification/revision/renewalapplication, the module 3 should be updated as described under section 5.Updated sections should be in line with the granularity chosen in the initial submission.

-         給EDQM缺陷信的回復(fù)或通知/修訂/更新申報(bào)：模塊3應(yīng)按第5部分所述進(jìn)行更新。更新后的部分應(yīng)與初始申報(bào)中所選的分層保持一致。

-         Anychanges to a previous sequence should be highlighted and shall allow printing.

-         應(yīng)著重顯示對(duì)之前序列的所有修改，并應(yīng)允許打印。

5.  Lifecyclemanagement of applications申報(bào)資料的生命周期管理

Forthe lifecycle of a CEP application, it is necessary to have at any time acurrent view of the approved dossier, and to maintain an appropriate granularity.Applicants are requested to implement the following requirements, which will bechecked at receipt at EDQM.

在CEP申報(bào)的生命周期中，有必要在任何時(shí)候都有一份已批準(zhǔn)文檔的當(dāng)前視圖，并保持適當(dāng)?shù)姆謱?。申?bào)人應(yīng)執(zhí)行以下要求， EDQM在接收時(shí)會(huì)執(zhí)行相關(guān)檢查。

5 .1 Granularity層級(jí)

Large sections should be subdividedinto smaller parts. For example, the CTD sections 3.2.S.2,and 3.2.S.4 should besubdivided into subsections according to annex 2. It is important that the dossier can beeasily navigated. The addition of too many subsections to Module 3 can resultin the dossier being difficult to navigate and may result in blocking atreceipt, thus delaying its treatment.

較大的部分應(yīng)拆分為更小的部分。例如，CTD部分3.2.S.2和3.2.S.4應(yīng)依據(jù)附錄2拆分為子部分。文檔易于導(dǎo)航是很重要的。在模塊3中增加太多子部分可能會(huì)導(dǎo)致文檔難以查找，可能就會(huì)導(dǎo)致接收障礙，從而延遲對(duì)其處理。

5.2     Updatedsections更新后的部分

Anyupdate of a CEP application (eg. response to EDQM deficiency letters orrequests for revision) should include the related updated sections and thelevel of granularity of the data submitted should be in line with the levelchosen in the last procedure (see annex 2). Updated pagesonly are not accepted (except if the complete CTD section is on one page).

一份CEP申報(bào)資料的所有更新（例如，對(duì)EDQM缺陷信的回復(fù)，或申請(qǐng)修訂）均應(yīng)包括相關(guān)的更新后的部分，并且所提交數(shù)據(jù)的分層應(yīng)與上次程序所選的層級(jí)相同（參見附錄2）。不接受只提交更新后的頁(yè)（除非完整的CTD部分就是只有一頁(yè)）。

For each update of the dossier andwhatever the submission format, the following instructions should beimplemented:

對(duì)于文檔中的每個(gè)更新，不管申報(bào)格式是什么，都要執(zhí)行以下要求：

-  Responsesto an EDQM deficiency letter: Module 1 and 3 should be updated. Module 1 shouldcontain the responses to the questions and supportive data; in Module 3 thecomplete updated sections affected by the Questions & Answer process shouldbe included (with the changes highlighted if applicable).

- 對(duì)EDQM缺陷信的回復(fù)：模塊1和模塊3均應(yīng)更新。模塊1應(yīng)包括對(duì)問題的回復(fù)和支持性數(shù)據(jù)；模塊3中應(yīng)包括受問答影響的完整更新后的部分（適用時(shí)應(yīng)著重顯示修改內(nèi)容）。

-  Notificationsor requests for revision/renewal: Module 1 and 3 should be updated. All sections fromModule 3 affected by the proposed change(s) at the relevant granularity levelshould be updated and the changes highlighted. A comparative table of theapproved & proposed data should be given in Module 1.

- 修訂/更新通知或申請(qǐng)：模塊1和模塊3均應(yīng)更新。模塊3中所有受擬定變更影響的部分均應(yīng)按相關(guān)層級(jí)更新，并著重顯示修改內(nèi)容。在模塊1中提交一份已批準(zhǔn)VS擬定數(shù)據(jù)對(duì)照表。

Specific instructions applyalso, depending on the submission format chosen:

具體要求依據(jù)申報(bào)格式不同還適用于：

-        Foran eCTD: foreach update a new sequence 000(X+1) should be provided containing Modules 1, 3as appropriate, with updated files in the relevant sections, using the samestructure and granularityas the original submission. The files should have the appropriateoperation attributes: “New”, “Replace”, “Delete”. The use of  the “Append” attribute should be avoidedsince it leads frequently to lifecycle difficulties.

-        對(duì)于eCTD：每個(gè)更新中，所提交的新序列000（X+1）均應(yīng)包括模塊1和3（適當(dāng)時(shí)），并在相關(guān)部分包括更新的文件，同時(shí)保持與原始申報(bào)中的相同結(jié)構(gòu)和分層。文件應(yīng)有適當(dāng)?shù)牟僮鲗傩裕?/span>“新增”、“替代”、“刪除”。應(yīng)避免使用“附錄”屬性，因?yàn)樗３?huì)導(dǎo)致生命周期維護(hù)困難。

-        For a NeeS: the Modules 1, 3 shouldbe provided as appropriate, with updated files in the relevant sections, usingthe same structure and granularityas the original submission, and with a table of content.

-        對(duì)于NeeS：應(yīng)提交模塊1和3，適當(dāng)時(shí)，還要提交相關(guān)部分中更新后的文件，需使用原始申報(bào)中的相同結(jié)構(gòu)和層級(jí)，同時(shí)提交一份目錄表。

-        For a PDF: in Module 3, the updatedsections should be supplied in one single pdf file, and the bookmarks should bein line with the original granularity of the dossier.

-        對(duì)于PDF：在模塊3中，更新后的部分應(yīng)以單個(gè)PDF文件提交，書簽應(yīng)與文檔的原始分層一致。

Onlythe necessary updated information should be sent, and no other changes to thecontent of the dossier should be introduced. Failure to submit a completedocumentationset in the appropriate modules and sections will block the assessment processand may ultimately lead to blocking or rejecting the application at receipt.

只需要發(fā)送更新后的資料，不應(yīng)引入對(duì)文檔內(nèi)容的其它修改。未能提交適當(dāng)模塊和部分中完整的系列文件將會(huì)對(duì)評(píng)審流程形成障礙，可能最后導(dǎo)致申報(bào)資料在接收時(shí)被阻或拒收。

5.3     Whento submit a baseline Module 3? 何時(shí)提交基準(zhǔn)模塊3？

Anelectronic “baseline” Module 3 is a consolidated picture of all the CTDsections corresponding to the regulatory information that has already beensubmitted and approved. If no baseline has been submitted so far, applicantsare strongly encouraged to submit a baseline application to EDQM to facilitatethe management of its lifecycle for both the applicants and the EDQM.

電子“基準(zhǔn)”模塊3是所有CTD部分的整合，它對(duì)應(yīng)的是已經(jīng)提交并批準(zhǔn)的注冊(cè)資料。如果截止目前尚未提交基準(zhǔn)，強(qiáng)烈建議申報(bào)人提交一份基準(zhǔn)申報(bào)給EDQM以便于申報(bào)人和EDQM對(duì)其進(jìn)行生命周期管理。

It is strongly recommended to submit abaseline Module 3 in the following circumstances:

強(qiáng)烈建議在以下情形下提交模塊3基準(zhǔn)模塊：

-        Switchfrom a paper to an e-submission

-        從紙質(zhì)轉(zhuǎn)為電子申報(bào)

-        Switchfrom a pdf/NeeS to an eCTD

-        從PDF/NeeS轉(zhuǎn)為eCTD

Itis strongly recommended to submit a baseline Module 3 at the time of a renewal,a revision or a notification.

強(qiáng)烈建議在更新、修訂或通知時(shí)提交基準(zhǔn)模塊3。

Onthe other hand a baseline Module 3will not be accepted duringthe course of a procedure (e.g. when responding to a deficiency letter or anyother information requested), nor when it is not linked to a regulatoryactivity (revision/renewal/notification).

另一方面，不接受在程序期間提交基準(zhǔn)模塊3（例如，在回復(fù)缺陷信時(shí)或要求提交其它信息時(shí)），也不接受沒有法規(guī)活動(dòng)時(shí)提交（修訂/更新/通知）。

6.  Validationby the EDQM  EDQM執(zhí)行的驗(yàn)證

Atreceipt of a submission by EDQM, a validation step is performed. Validationincludes verification of the submission format, compliance with therequirements described in this guidance document and in EU validation rules forNeeS and eCTD. The most frequent issues which may lead to block a dossier atreceipt and consequently delay the start of assessment are summarised in Annex 5.

EDQM收到申報(bào)資料時(shí)，會(huì)執(zhí)行一個(gè)驗(yàn)證步驟。驗(yàn)證包括核對(duì)申報(bào)格式，核對(duì)是否符合本指南文件和NeeS與eCTD的EU驗(yàn)證規(guī)則中所述的要求。附錄5中總結(jié)了可能會(huì)導(dǎo)致文檔在接受時(shí)受阻從而導(dǎo)致審評(píng)開始延遲的最常見問題。

7.  Routes(or pathways) of submission申報(bào)提交途徑（通道）

Electronic submissions should be submittedthrough the “Common European Submission Portal” (CESP). Users shouldfirst register with the CESP (https://cespportal.hma.eu) before sendingsubmissions to the EDQM.

電子申報(bào)資料應(yīng)通過“歐洲通用申報(bào)端口”（CESP）提交。用戶應(yīng)先在CESP注冊(cè)（https://cespportal.hma.eu）再將資料通過該端口發(fā)送至EDQM。

8.   Security安全

The files submitted should not haveany password protection, encryption or other security settings; such files willnot be accepted at the validation phase at EDQM. The applicant should check anyelectronic submission for absence of virus before sending it to EDQM.

所提交的文件不應(yīng)有任何密碼保護(hù)、加密或其它安全設(shè)置。此類文件在EDQM接收驗(yàn)證時(shí)無法接受。申報(bào)人在發(fā)送電子申報(bào)資料給EDQM之前應(yīng)檢查確保無病毒。

TheEDQM guarantees the security and confidentiality of data from receipt.

EDQM保證接收數(shù)據(jù)的安全性和機(jī)密性。

9.  Annexes:附錄

英文原文官網(wǎng)鏈接 https://www.edqm.eu/sites/default/files/guidance_for_esubmissions_for_cep_applications-january2018.pdf

申報(bào)表也有相應(yīng)修改，表1為新申報(bào)，表2為修訂/更新

申報(bào)表1鏈接https://www.edqm.eu/sites/default/files/application-form-new-applicant-cep-form055.doc

申報(bào)表2鏈接 https://www.edqm.eu/sites/default/files/application-form-revision-renewal-cep-form056.doc