Guidance for Industry on Providing Regulatory  Information in eCTD Format
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Guidance for Industry on Providing Regulatory Information in eCTD Format

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    Guidance for Industry on Providing Regulatory  Information in eCTD Format Guidance for Industry on Providing Regulatory Information in eCTD Format Document Transcript

    • Guidance for Industry Version 1.2 1/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 Guidance for Industry on Providing Regulatory Information in eCTD Format Authors: SIMES Working Group “Specification & Best Practice Guidance” Lead: Susanne Kienberger, Swissmedic Claudia Zerobin, Swissmedic Cornelia Bigler, Swissmedic Damian Schöni, Swissmedic Rosemarie Sift Carter, Swissmedic Charles Boyle, Swissmedic Jörg Schnitzler, Astellas Caroline Keller, Novartis Francis Le Monnier, Novartis Inge Sift, Alpinia Philippe Karl, Genzyme Andrew Marr, GlaxoSmithKline Françoise Fedele, sanofi-aventis (schweiz) ag Dorothée Alfonso, sanofi-aventis (schweiz) ag Sibylle Stettler, Rexult AG Responsible: Support, Marketing Authorisation, Swissmedic Version / Date: Version 1.2 / 29.11.2010 Document Control Change Record Version Date Comments Author(s) 0.92 15.06.2009 Draft version, published on Swissmedic website SIMES Working Group 1.0 30.10.2009 1st valid version, published on Swissmedic website SIMES Working Group 1.09 26.03.2010 Draft for Review SIMES Working Group 1.1 21.05.2010 Update, published on Swissmedic website SIMES Working Group 1.19 05.11.2010 Version for Review SIMES Working Group 1.2 29.11.2010 Version published on Swissmedic website SIMES Working Group Reviewers Version Date Organisation 0.92 15.06.2009 Review team SGCI, Review team Swissmedic 1.0 30.10.2009 Review team SGCI, Review team Swissmedic 1.09 26.03.2010 Review team SGCI, Review team Swissmedic 1.1 21.05.2010 Review team SGCI, Review team Swissmedic 1.19 05.11.2010 Review team SGCI, Review team Swissmedic 1.2 12.11.2010 SIMES Step 3 Working Group
    • Guidance for Industry Version 1.2 2/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 Distribution Version Date Name 0.92 15.06.2009 Official publication on Swissmedic website 1.0 30.10.2009 Official publication on Swissmedic website 1.09 26.03.2010 Project team and Review teams SIMES 1.1 21.05.2010 Official publication on Swissmedic website 1.19 05.11.2010 Review team SGCI, Review team Swissmedic 1.2 29.11.2010 Official publication on Swissmedic website
    • Guidance for Industry Version 1.2 3/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 Table of Contents 1  Introduction 7  Timelines 7  2  Purpose and scope 8  2.1  Types of products 8  2.2  Types of submissions 8  2.3  Additional information and subsequent submissions 8  2.4  Filing formats of submissions in eCTD format 8  3  Structure and content of submissions in eCTD format 9  3.1  Structure 9  3.1.1  eCTD Identifier........................................................................................................9  3.1.2  Sequence number folder.........................................................................................9  3.1.3  util and dtd subfolders...........................................................................................10  3.1.4  Module 1 subfolder................................................................................................10  3.1.5  Modules 2 to 5 subfolders.....................................................................................10  3.2  eCTD envelope 10  3.3  Metadata 11  3.4  Inclusion of correspondence documentation 12  3.5  Cover Letter 12  4  Technical requirements for submissions 14  4.1  Submission media 14  4.2  Compression and password protection / security settings 14  4.3  PDF files 15  4.4  File naming conventions 16  4.5  Hyperlinks 16  4.6  md5 checksum 17  4.7  Additional files in Word format 17  4.8  Virus check 18  4.9  Technical validation before submission 18  5  Life cycle management 19  5.1  Life cycle management at the “Drug Product” layer (eCTD application) 19  5.2  Life cycle management at the submission layer (i.e. eCTD-sequence) 19  5.3  Life cycle management at the document layer (eCTD leaf) 19  5.4  Life cycle management of specific documents 19  5.5  Responses to “List of Questions” 20  6  Baseline submissions 21  7  Submission of PSURs and E2E / RMP Updates in eCTD Format 23  7.1  PSUR 23  7.1.1  Application type “PSUR” -> please fill in the Form PSUR for Human Medicinal Products.............................................................................................................................23  7.1.2  Application type “Supplemental Information“ ........................................................23  7.2  E2E / RMP Update 23  7.2.1  Application type “PSUR” if submitted as part of the regular PSUR Program .......23  7.2.2  Application type “Supplemental Information” if not submitted as part of the regular PSUR Program ..................................................................................................................23  7.3  Structure for a PSUR submission as part of the regular PSUR Program 24 
    • Guidance for Industry Version 1.2 4/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 8  Test eSubmissions 25  9  Shipment 26  10  Appendices 27  Appendix 1: eCTD Reference Documents 27  Appendix 2: Swissmedic types of applications 28  Appendix 3: List of documents requested additionally in paper format 30 
    • Guidance for Industry Version 1.2 5/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 Glossary A brief glossary of terms (for the purpose of this document only) is indicated below: Term Definition Applicant A pharmaceutical company or its agent that is submitting information in support of an application. Applicant’s information Regulatory information submitted by an applicant for or to maintain a marketing authorisation that falls within the scope of this guidance document Application A collection of documents compiled by a pharmaceutical company or its agent in compliance with Swiss legislation and guidelines in order to seek a marketing authorisation or any amendments thereof. An application may comprise a number of submissions. Application number The application number is assigned to the application by Swissmedic. It tracks the application at the agency level. A submission can consist of several application numbers. eCTD identifier An eCTD identifier is a name, code or number used as the directory name in the top-level directory. This can be a proposed trade name, a company internal project code, or the Marketing Authorisation number. eCTD-Sequence All files and folders in a submission in eCTD format are to be placed under the eCTD-Sequence number folder (equivalent to the term "sequence" used by the EMA) eCTD-Submission An eCTD-Submission is an electronic-only submission in the eCTD format that is supported by paper documents (except some documents from Module 1). Marketing Authorisation Number The Marketing Authorisation Number is the unique identifier for the medicinal product and the dosage form for the Swiss market. (Swissmedic Number) Submission A single set of information and/or documents supplied by the applicant as a partial or complete, application. In the context of eCTD, this is equivalent to ‘eCTD Sequence’. Test-eCTD-Submission A Test-eCTD-Submission is an electronic-only submission by the applicant prior to the official submission. The objective to test the technical attributes and suitability of the eCTD. A Test- eCTD-Submission may differ from the official submission and be incomplete. A test submission cannot be accepted as the true submission for review.
    • Guidance for Industry Version 1.2 6/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 List of Abbreviations ATC Anatomical Therapeutical Chemical CCDS Company Core Data Sheet CL Checklist CTD Common Technical Document DMF Drug Master File DTD Document Type Definition eCTD electronic Common Technical Document EMA European Medicines Agency EU European Union FO Form GMO Genetically Modified Organisms ICH International Conference on Harmonization INN International Non-proprietary Name LCM Life cycle management LoQ List of Questions NeeS Non-eCTD electronic submission PDF Portable Document Format PSUR Periodic Safety Update Report RMP Risk Management Plan (E2E) Q&A Questions and Answers document SIMES Project “Solution for the Implementation and Management of Electronic Submissions” SmPC Summary of Product Characteristics STF Study Tagging Files Swissmedic Swiss Agency for Therapeutic Products ToC Table of Contents TPA Therapeutic Product Act (Federal Law on Medicinal Products and Medical Devices) of December 15, 2000 / SR 812.21 Bundesgesetz vom 15. Dezember 2000 über Arzneimittel und Medizinprodukte (Heilmittelgesetz HMG) in the past known as LTP (Law on Therapeutic Products) Util Utility folder in the eCTD Sequence. Contains technical files. VAM Ordinance on Medicinal Products of October 17, 2001 / SR 812.212.21(Verordnung über die Arzneimittel) XML Extensible Markup Language
    • Guidance for Industry Version 1.2 7/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 1 Introduction This document aims to provide guidance on the Swiss Agency for Therapeutic Products (Swissmedic) plans to implement electronic-only submissions with the electronic Common Technical Document (eCTD). It is to be used in the preparation and filing of medicinal product submissions to Swissmedic in the eCTD format established by the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. This Guidance Document reflects the current situation and will be regularly updated to reflect changes in national legislation and/or ICH regulations together with further experience gained within different types of submissions submitted in electronic format. The relevant guidances on the same topic, issued by EMA and Health Canada, have been considered in the preparation of this document and used as a basis. The preparation and filing of submissions as well as additional information in eCTD format is encouraged but remains optional. Applicants who choose to file a submission in the eCTD format must comply with the requirements for such submissions, these are  the requirements defined in this guidance document  the Swiss M1 Specification for eCTD  the Electronic Common Technical Document Specification (current Version), developed by the ICH M2 Expert Working Group (EWG)  the Swiss eCTD validation criteria Submissions and additional information in electronic format that do not comply with these requirements, like non-eCTD electronic submissions (NeeS) will be rejected. This guidance document is supplemented and actualized by the Questions and Answers document on the Swismedic website (www.swissmedic.ch), which will be updated on a regular basis. Additionally, further eCTD Q&A issued by the ICH can be found at http://estri.ich.org/eCTD/index.htm Applicants are also encouraged to consult the list of publications and guidances published by European Regulatory Authorities. A non exhaustive list is attached as Appendix 1 for information. Timelines Electronic-only submissions for a defined number of application types are accepted since 1 January 2010.
    • Guidance for Industry Version 1.2 8/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 2 Purpose and scope The purpose of this guidance document is to integrate the eCTD format within the Swissmedic registration framework by describing the electronic format requirements for drug submissions filed pursuant to the Therapeutic Product Act (TPA) and all relevant ordinances. 2.1 Types of products This guidance document applies to pharmaceuticals, biologicals and vaccines, blood and blood derivatives as well as products pertaining to complementary medicines for human use. It does not apply to veterinary medicinal products and transplant products, medical devices and drug-device combinations where the combination product is classified as a device, as well as for simplified authorisation procedures for complementary and herbal medicinal products, especially application procedures for homeopathic and anthroposophic or Asian medicinal products without indication. The eCTD format is also encouraged for the drug component of drug and device combinations, where the primary mechanism of action is drug-related. 2.2 Types of submissions The currently applicable submissions are listed in Appendix 2. This guidance document does not currently apply to pre-marketing authorization documents (e.g. briefing books for scientific advice meetings) or Notification Applications for Clinical Trials. 2.3 Additional information and subsequent submissions Once an applicant files a submission in the eCTD format, all additional information and subsequent submissions for the same drug product should be filed in the eCTD format (“once eCTD, always eCTD”). Applicants should not revert to the paper-based CTD format for additional information and subsequent submissions for the same drug product. 2.4 Filing formats of submissions in eCTD format The filing using eCTD is foreseen as an electronic only submission. For legal reasons however distinct documents of Module 1 such as listed in Appendix 3 have to be sent in addition as signed original paper version. The paper version is to be arranged in the same order as the electronic version. The current Swissmedic practices have to be taken into account to define which documents are needed for the submission types, and the documents detailed in Appendix 3 should be provided where applicable. For any guidance about which documents are needed for which application, please refer to the TPA and related ordinances and the website of Swissmedic.
    • Guidance for Industry Version 1.2 3 Structure and content of submissions in eCTD format 3.1 Structure The content of information required for submissions in eCTD format is the same as for paper- based submissions in CTD format. However, the location of files in the submission in eCTD format may differ from the location of the paper documents in the submission in CTD format. The eCTD structure reflects the XML backbone that is used for the submission. The eCTD structure can be graphically displayed by an XML viewing tool. Figure 1 illustrates a portion of the eCTD structure, as seen using an XML viewing tool. Sequence Number Folder Module 2 Subfolder Leaf Files Figure 1: eCTD Structure 3.1.1 eCTD Identifier There is no requirement to use an identifier for the directory name in the top-level directory. However in order to facilitate the handling of the submissions, Swissmedic recommends to use the proposed trade name or a company internal project code as an identifier. Once defined, it should remain unchanged during the whole lifecycle. 3.1.2 Sequence number folder All files and folders in a submission in eCTD format are to be placed under the sequence number folder, as described in the ICH Electronic Common Technical Document 9/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12
    • Guidance for Industry Version 1.2 10/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 Specification, “File Names and Directory Structure”. The sequence number folder should be named using a four-digit number. The sequence number for the first submission should be 0000. Applicants are to provide an incremental number, unique within the same application for each new sequence they provide. If a submission fails technical validation due to a technical error, the sequence number does not change when the submission is filed again. If the submission passes technical validation, but has content deficiencies, resolving these deficiencies requires an increment to the sequence number. The sequence number folder includes an m1 subfolder, m2–m5 subfolders (optional), and an util subfolder (see Figure 1). The eCTD backbone file (index.xml), the checksum file (index- md5.txt) and the util subfolder should be in the sequence number folder. 3.1.3 util and dtd subfolders The util subfolders contain a dtd subfolder as well as a style folder and they must only contain the files that are mentioned in the Swiss Module 1 Specification which define the regional Module 1 backbone file. The dtd subfolder located under the root folder must only contain the ICH eCTD DTD that defines the eCTD backbone file. The style folders must contain the relevant style sheet information. 3.1.4 Module 1 subfolder The content of the Module 1 is described in detail in the document Swiss M1 Specification for eCTD. 3.1.5 Modules 2 to 5 subfolders The structure and content of the Modules 2 to 5 subfolders (m2–m5) are defined in the ICH Electronic Common Technical Document Specification. The following points are to be considered:  Node extensions are allowed but should be used only where necessary  Node extensions are recommended for each clinical study report. The title element for the node extension is used to provide the full study title  The use of Study Tagging Files (STF) is discouraged. If STFs are present, please liaise with Swissmedic before submission. 3.2 eCTD envelope The metadata provided by the applicant with the eCTD are extremely important, since it indicates relationships between individual sequences for effective lifecycle management of the application. The particular envelope elements used by the review tool for display and management of submissions are listed in the Swiss Module 1 Specifications for eCTD, Appendix 2. Applicants must include and present metadata in a manner that unequivocally ties them to a submission (e.g. applicant name, INN). It is appreciated that there may be legitimate reasons for the metadata to change over the lifecycle of the product and this is technically supported. Consistency, quality and accuracy of metadata should always be assured. When the Marketing Authorisation number is known, it should be included in the envelope.
    • Guidance for Industry Version 1.2 11/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 The field <submission description> is a free text field and serves to link the application number to the application, in case of more than one application per eCTD Sequence. Using the <application description> element, submissions relating to multiple parallel variations can be easily identified and grouped together. The contents of the <application description> element should therefore be concise but clearly indicative of the substance of the application in question. The <application description> can also serve to determine the differences between sequences where the same value for <application type> must be used for multiple submissions (e.g. ”variation requiring authorization incl. scientific review” due to the fact that a completely exhaustive set of values for <application type> is not implemented in the eCTD Swiss M1 specification). As an example, “new indication” as application type is not descriptive enough for the content and therefore the description should be supplemented by “application for new indication breast cancer” in the <application description> field. 3.3 Metadata The leaf attribute metadata provided by the applicant is considered important, since this information is displayed by review tools and is used for identifying documents and sections, and becomes particularly important in managing the lifecycle of the submission. For example, the ICH eCTD Specification, v3.2 describes 6 eCTD Heading Element Attributes for use in the eCTD to structure the eCTD content. Five of these attributes are in Module 3:  Substance  Drug Product/Drug Substance Manufacturer  Product Name  Dosage Form  Excipient These attributes correspond to elements in the eCTD that may be repeated, and are used to define specifically what each repeated section covers. For example, in an eCTD covering two active ingredient manufacturing sites, the directory structure for the eCTD may be splitted into two paths which will contain documents for the different sites, and the XML will be similarly structured (see p6-11 of the ICH eCTD Specification, v3.2). The extent to which a single eCTD can cover multiple substances, manufacturers, products and excipients, and the use of these attributes to describe what is being covered is largely left to the applicant. This means that the eCTD can be structured in different ways. These potential variations in structure and scope can affect the presentation of the dossier using eCTD review tools that ‘read’ the XML, and affect eCTD repositories that are used to store the eCTD files and directory structure. The structure of an eCTD will affect how the lifecycle of the eCTD can be managed over time, and, therefore, the structure of the first eCTD for a product or product range needs careful consideration. For example, if an eCTD is built to cover 100mg and 200mg tablets, and common documents are submitted for both strengths, if a line extension is introduced to add a 150mg tablet, then the applicant needs to decide whether to replace 100/200mg documents with a 100/150/200mg document, or to create a new standalone 150mg document and introduce another 32p and 23p section to the existing eCTD. Another option would be to build an entirely different and new eCTD for the 150mg tablets.
    • Guidance for Industry Version 1.2 12/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 3.4 Inclusion of correspondence documentation The term ”correspondence” applies to all communications (documents) that are exchanged between an applicant and a regulator in the context of an authorisation procedure but which do not have a formal designated placeholder within the eCTD structure. For example, responses to authority questions are not classified as ‘correspondence’ since the Swiss M1 eCTD DTD includes a designated section for such information. Not all correspondence should be included in the eCTD. This is because the eCTD exchange is currently one way only (from the applicant to the agency), and not all correspondence is directly relevant to the application dossier. Accordingly, only the minimum of correspondence that relates directly to the content of the dossier should be included in submissions to Swissmedic. All other correspondence should be exchanged outside the eCTD via the usual means (letter). Where correspondence acknowledges the final change to details submitted in the body of the dossier, the agreement cannot be documented by that correspondence alone. The revised information should be provided in an accompanying replacement document situated in the appropriate place in the body of the dossier, with the relevant information contained in a cover letter. 3.5 Cover Letter Submissions as well as additional information in eCTD format should be accompanied by an administrative cover letter in both paper and portable document format (PDF). The cover letter should always state the context of the submission, e. g. the application type and the marketing authorization number and the application number (Fill in with “pending” if not yet known.). The paper and PDF cover letters should have the same content. The cover letter in the submission in eCTD format is located in the folder 1.0 of the Swiss Module 1. The cover letter should be submitted with the document operation attribute “new”. As eCTD viewing tools will display all "new" leaf elements in a current or cumulative view, it is recommended that you place additional descriptive text in the leaf title to help you identify specific cover letters. This will help identify each cover letter leaf and the submission it is in, rather than having the cover letters named the same in each sequence. Some examples for the leaf titles could be: Cover Letter for Sequence 0000 Cover Letter for New Indication AML The printout of the checksum file (index-md5.txt) should be attached as an annex to the cover letter (paper version). The annex must be dated and signed. The letter should at least contain the following information:  Date  The applicant’s name and address  The product (invented) name(s)  Marketing authorization number (if available)  Application number (if available)
    • Guidance for Industry Version 1.2 13/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12  ATC code( if available)  Dosage form  Dosage strength(s)  The International Non-proprietary Name (INN) of the product  The application type  A description of the submission  Attestation concerning mock-ups (if applicable)  Number of CDs/DVDs provided  Contact details in case of technical validation issues The following statements must be included:  “We confirm that the CD/DVD-burning session is closed and the submission is checked with an up-to-date and state-of-the art virus checker: [name of the antivirus software and version of the virus checker]”  “We confirm that the documents submitted in electronic form and the corresponding paper version of parts of Module 1 are identical.” The tracking of the submitted sequences in a tabular format should be included in the cover letter or as an annex to the cover letter, as per the following example: Date of submission Sequence number Related eCTD sequence Regulatory activity / Type of claim Regulatory status (submitted / approved / rejected The letter (paper version) must be signed. If there are specificities concerning the eCTD submission about which the reviewers should be informed, it is highly recommended to include in the cover letter or as an annex to the cover letter an eCTD ”Reviewer’s Guide” or similar document, that may contain the following sections if applicable, in addition to those specified above:  Particularities relating to presentation and delivery of the eCTD (hard media)  Information on file sizes by module  Data security/virus scan information  Legacy documents and scanned pages details  File formats (if any particularities to report)  File size (if exceeding 100MB restrictions)  Files referenced at multiple locations within the backbone  Specifications adhered to  Documents with relevance to more than one CTD-module  Hyperlink appearance and strategy  Bookmarks  Particularities of module organisation  List of documents available on request
    • Guidance for Industry Version 1.2 14/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 4 Technical requirements for submissions 4.1 Submission media Hard media (e.g. CDs, DVDs) must be used for the submission of all eCTDs. CD (CD-ROM) conforming to ISO 9660 or ISO 13346 can be accepted. Swissmedic will not accept any hardware (laptops, desktops, zip drives, etc.) from applicants in connection with the submission of information in electronic format. The electronic information or eCTD should be directly readable and usable on Swissmedic’s hardware (e.g. CD/DVD drive) using its own software. It is the policy of Swissmedic to maintain desktop configurations and IT infrastructure in line with common office standards. In the case of a large application, provision of a single DVD over multiple CDs is strongly recommended by Swissmedic, as this allows the technical validation and loading into the repository directly from the hard media, without the need to first recompile the eCTD submission on a server. Should the provision of a single CD or DVD not be possible, and if multiple CDs must be used for large applications, individual modules should not be split over multiple CDs (e.g. if possible, Module 1 should be contained on a single CD, Module 2 should go onto the next CD even if this requires CD 1 not to be filled to capacity and so on). Where a split over multiple CDs is inevitably necessary, subfolders should be distributed in sequence, and these subfolders should not be split between CDs. In this case the submission of a DVD should be considered. The submission media should be packed adequately to prevent damage to the media. All the contained media units should be appropriately labeled as described below. Each CD or DVD submitted with an eCTD should include the following label information, clearly presented and printed on the media:  The applicant’s name  The product (invented) name(s)  The marketing authorisation number (if available)  The application number (if available)  The International Non-proprietary Name (INN) of the product  The sequence number(s) of the eCTD submissions contained on the CD/DVD  The submission date (YYYY-MM)  The Number of CDs or DVDs per full set and an indication of the place of the individual CD/DVD within this set  The application type of each eCTD submission(s) contained on the CD/DVD, as per the eCTD envelope information.  A brief description of each submission type of each eCTD submission(s) contained on the CD/DVD (e.g. “new sequence following validation”) 4.2 Compression and password protection / security settings The applicant is required not to apply any compression to the submission or the files inside the submission. Therefore the data on the media should not be packed into a zip-file, rar-file or any other file that has been compressed.
    • Guidance for Industry Version 1.2 15/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 One-time security settings or password protection of electronic submissions for security purposes is not acceptable during transportation from the applicant to Swissmedic. Applicants should also not include any file level security settings or password protection for individual files in the eCTD. The file settings should allow printing, annotations to the documents, and selection of text and graphics. Internal security and access control processes in the regulatory authority will maintain the integrity of the submitted files. Encryption is not considered necessary if the information is sent using a physical media. The applicant should assume all responsibility for the media until it is delivered to Swissmedic. The following points should be noted in relation to security:  The physical security of the submission during transportation/transmission is in the responsibility of the applicant.  Once received by Swissmedic, security and submission integrity is the responsibility of the agency. The use of, and subsequent validation of the MD5 checksum allows the recipient of the eCTD to ascertain whether files in the submission have been changed since the checksum was generated. 4.3 PDF files Portable Document Format (PDF) is an electronic format that is open, de facto, and published and created by Adobe Systems Incorporated (http://www.adobe.com). No specific products from Adobe or any other company are necessary to produce PDF documents. The following points can be made in relation to PDF files:  Files should be PDF v1.4 and should be legible with the Acrobat Reader search plug in or any other freeware viewer; PDF files should be saved as ”Optimized” to reduce the size and allow faster opening when viewed via an internet connection. The use of additional software to navigate and work with the files is not acceptable, unless agreed upon with Swissmedic.  In exceptional cases other PDF versions can be used (e.g. old documents created with a previous version of Adobe), provided these can be opened and read by Swissmedic. The use of other PDF versions needs to be justified in the cover letter.  PDF files produced from an electronic source document are preferred to PDF files generated from scanned paper since such 'electronic' PDF files provide the maximum functionality to the reviewers in terms of search capabilities and copy & paste functionality.  Expert Reports and the Overviews/Summaries in the CTD Module 2 should always be generated from an electronic source document.  If scanning is unavoidable, readability and file size should be balanced; the following is recommended: resolution 300 dpi (photographs up to 600 dpi), avoid grayscale or color where possible, use only lossless compression techniques.  The maximum individual acceptable file size is approximately 100 MB. The file size should ensure clarity, speed of download and ease of review. Further guidance should be sought from Swissmedic regarding individual larger files as to their acceptability.
    • Guidance for Industry Version 1.2 16/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12  Fonts should be chosen of a type, color and size such that they allow easy reading of documents on screen (1024 x 768 pixels) or after printing; examples of such font-types are: o Times New Roman, 12-point, black o Arial, 10-point, black.  All fonts used in a document (except Times New Roman, Arial and Courier) should be embedded, including all the characters for the font. Swissmedic advises to limit the number of fonts used in a document and to avoid customized fonts.If colors other than black are used, color reproduction after printing should be tested before submission; the print area for pages should fit on an A4 sheet of paper; margins should allow binding in multi-ring binders without affecting readability. Additional details on PDF can be found in the ICH eCTD Specification Document, App. 7. 4.4 File naming conventions It is recommended to use the eCTD file naming conventions described in the ICH M2 eCTD Specification and the Swiss Module 1 Specification for eCTD. If an applicant wishes to submit multiple files in one section, where only one highly recommended name is available, this can be achieved using a suffix to the filename (e.g. pharmaceutical-development-container.pdf). 4.5 Hyperlinks In general, hypertext links are encouraged within the eCTD to facilitate swift navigation within the dossier, but should not be overused. The eCTD should be structured and links provided in such a way as to ensure that the reviewer is constantly aware of the overall structure and narrative flow of the dossier. For example, Module 3 is highly structured and defined to a relatively low level of granularity in the specification. Therefore, only minimal use of hyperlinks should be necessary. For example, when the same citation appears on a page more than once, it is recommended that a link only to the first instance of the citation per page is provided. The greater the number of hyperlinks contained in an eCTD dossier, the longer it takes to technically validate the submission, and the greater the likelihood of non-functioning hyperlinks. The use of ”obvious” and therefore redundant external links is discouraged with a view to future lifecycle management. However, if hyperlinks are only to be included where considered necessary and considered to add real value, it is important that the way in which the eCTD titles (i.e. the backbone entries visible as the eCTD “ToC”) are used is consistent with how the documents themselves are referred to within other documents, for example summary documents. If the title presented by the review tool in the eCTD ToC and the reference in a summary document do not match, then this negates the use of the backbone and a hyperlink is needed. In the Non-clinical/Clinical part of the eCTD, the structure is less well defined. Within Modules 4 and 5 the localization of studies and references may vary across submissions. For fast orientation linking from summaries is of benefit. Since changes occur rarely to already- submitted content in Modules 4 and 5 in contrast to Modules 3 the issue of out-dated links over the application lifecycle is therefore less critical.
    • Guidance for Industry Version 1.2 17/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 4.6 md5 checksum A checksum (MD5) should be included for each file in the eCTD, allowing the recipient to verify the integrity of physical files in the submission. An MD5 checksum of the XML eCTD index (index.xml) should also be included. Applicants should name this checksum file index-md5.txt, and include it as a file (with one line of content and with no header line) in the same directory as the XML eCTD instance. An invalid checksum will result in the rejection of an eCTD submission as technically invalid. 4.7 Additional files in Word format Swissmedic requires Word documents (.doc – no .docx) for the following documents, in addition to the PDF for the purposes of review and document manipulation:  Module 2.3 Quality Overall Summary  Module 2.4 Nonclinical Overview  Module 2.5 Clinical Overview  Module 1.3: o Information for Professionals o Patient Information  Module 1 Responses to Swissmedic LoQ  Module 1.5.1 Swiss Bioequivalence Trial Information Form  Module 1.2.2.16 Form PSUR for Human Medicinal Products PDFs (and other accepted file formats) only are to be referenced in the eCTD XML backbone. Word documents should not be included in the eCTD backbone, as they are provided merely as an aid to review. An inclusion within the eCTD would result in an unnecessary management of the lifecycle of these documents in addition to the formal PDF documents. Word files should be placed on the same data carrier, alongside the 0000 (or appropriate) eCTD sequence, not within it. The folder should be called “<eCTD sequence>-workingdocu- ments” (e.g. 0000-workingdocuments)” with a substructure as follows:  0000-Product information  0000-Module 2 - 2.3 - 2.4 - 2.5  0000-Responses to questions  0000-Forms Within this folder, for the following files in Word format, the following naming convention applies:  For the information to professionals: prof_productname_submissiontype_date.doc  For the patient information: patient_productname_submissiontype_date.doc
    • Guidance for Industry Version 1.2 18/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12  For Modules 2.3 to 2.5: The Word documents should have the same name as the submitted pdf files with the extension .doc instead of .pdf, and should follow the same granularity where a subdivision into several documents exists.  For Responses to Swissmedic LoQ rtoq_submissiontype_date  Swiss bioequivalence information trial form bioequivalence_date.doc 4.8 Virus check The applicant is responsible for checking the submission for viruses and for informing Swissmedic of the type of software used for this purpose. Checking should be performed with at least one, but preferably more, up-to-date virus-checkers and a statement in the cover letter should be included (see chapter 3.5) After receipt at Swissmedic, a similar, multiple program, internal virus check will be performed. A positive check will result in the refusal of the eCTD. 4.9 Technical validation before submission Swissmedic requires that applicants use a validator that checks the submission for technical interoperability before submission. (Free-of-charge validation tools for the Swiss eCTD specification are available. For more detailed information please refer to the Swissmedic eSubmission website). To ensure efficient checking for technical correctness in Swissmedic applicants are required to comment severity B and severity C errors in a separate form provided by Swissmedic. The form technical validation (English only) is also available on the Swissmedic eSubmission website. The form is not part of the eCTD Module 1 and should not be integrated in the eCTD. One paper copy of the form has to be submitted together with the eCTD sequence to Swissmedic. Please be aware that a not properly completed form may lead to a rejection of the submission. Further details on the validation criteria are described in the document “Swissmedic eCTD Validation Criteria”.
    • Guidance for Industry Version 1.2 19/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 5 Life cycle management 5.1 Life cycle management at the “Drug Product” layer (eCTD application) An initial filing is usually defined as having a sequence number of 0000. There are some circumstances in which an initial filing might be filled with a sequence number other than 0000. Each further submission for the corresponding Drug Product will be done with an incremental eCTD sequence number. 5.2 Life cycle management at the submission layer (i.e. eCTD-sequence) The related eCTD-sequence-number describes the relationship of additional information to the original submission or subsequent submissions. For all new drug submissions types in eCTD format, the related eCTD-sequence-number in the envelope and in the cover letter (tracking table) should be left empty. For subsequent submissions, it is mandatory to include a related eCTD-sequence. The related eCTD-sequence-number should be the sequence-number of the submission to which the additional information applies. The related eCTD-sequence-number should only be one single eCTD-sequence number. See “Example of the use of the Related Sequence” in Appendix 2 of Swiss Module 1 Specification for eCTD. 5.3 Life cycle management at the document layer (eCTD leaf) The operation attribute describes the relationship between leaf files in submissions subsequent to the original submission and in additional information related to those submissions. (For an orginal submission only the operation attribute “new” is applicable). The four LCM activities (operation attributes) provided by the ICH are new, replace, delete and append. Further information can be found in the ICH Electronic Common Technical Document Specification. The operation “append” should be used with caution in view of future LCM issues. 5.4 Life cycle management of specific documents Responses to List of Questions and adaptations of product information files are handled with new eCTD Sequences. For life cycle management at the document layer, the operation attribute should be treated as described below for specific documents. For the cover letter leaf elements provided with all eCTD-sequences, the operation attribute should always be “New.” For the form Application / Variation leaf element,  when provided with all submission types, the operation attribute should be “New”  when provided as additional information for a correction of an error in the ZL000_00_003 form in response to Swissmedic List of Questions (LoQ), the operation attribute should be “Replace”.
    • Guidance for Industry Version 1.2 20/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 For the Product Information (Information for Professionals, Patient Information, elements of packaging materials) leaf elements:  when provided with the initial application (sequence 0000) the operation attribute should be “New”  when provided with all other submission types, the operation attribute should be “Replace” (exception: sequence 0000)  when provided as additional information in response to the LoQ, the operation attribute should be “Replace”  when a new eCTD-sequence, which includes the final Product Information documents, is provided as additional information the operation attribute should be “Replace”. 5.5 Responses to “List of Questions” In the case the original submission is made using the eCTD format, and where a List of Questions (LoQ) has been issued by Swissmedic, the responses to the LoQ have also to be provided in eCTD format. The document which lists all the questions with the corresponding narrative text response for each question should be placed in the “Responses to Swissmedic LoQ” section of M1. Where responses also contain new or updated data/documents relating to Modules 3, 4 and/or 5, such data/documents should be placed in the relevant sections of those Modules. This may also apply to Module 1 (e.g. revised product information), as well as to Module 2 in cases where extensive data/documents would require inclusion of the relevant summaries and/or overview sections. Where new or updated documents are required, hyperlink(s) from an appropriate location(s) in the consolidated LoQ document to the new or updated document(s) elsewhere in the eCTD dossier should be included.
    • Guidance for Industry Version 1.2 21/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 6 Baseline submissions It is highly recommended that an eCTD baseline submission is submitted in electronic format, for applications previously managed in paper or other electronic formats. There is no obligation to submit a full, reformatted eCTD for already authorized products. However, the Marketing Authorization holder may provide Swissmedic with information reformatted as eCTD for their already authorized products. In particular Swissmedic encourages the submission of reformatted quality information in eCTD, in order to facilitate the handling of variations. A signed declaration must also be submitted as an annex to the cover letter stating that the content/data of the submitted quality module in eCTD format is identical to the current approved quality part and that there have been no changes to the dossier content as a result of the provision of an eCTD submission. To start an eCTD product life cycle at a point other than with a new application, such as a variation or renewal, it is highly recommended to submit a separate initial baseline submission. For a baseline submission, the envelope attribute “application type” for a baseline submission should be “reformat“. Should the applicant submit additional changes, the envelope element “application type” for a baseline submission will be that corresponding to the proposed change (see Swiss M1 Specification for eCTD). In the majority of cases, an eCTD baseline submission will be provided as sequence 0000 for a product where there has been no previous eCTD submission, however for a product with an ongoing lifecycle Swissmedic would also accept a baseline submission within the lifecycle; for example if an applicant has submitted a new indication in eCTD format without baseline and at a later stage starts some variations of module 3 with a baseline submission. The theoretical five following options exist for a baseline submission however only options 1 to 4 are allowed as Module 1 as a minimum should be included. Option to deal with the legacy Legacy sequence(s) no. Variation sequence no. 1 Rebuild of the complete previous CTD paper life cycle 0000 - 0035 0036 2 Baseline submission of legacy as “current active view” 0000 0001 3 Partial baseline of Quality legacy part at the beginning of transition 0000 0001 4 Partial baseline (Quality/CMC part) in the middle of eCTD lifecycle - 0035 0000 – 0034 0036 5 No baseline at all n.a. 0000 It is expected that option 1 will rarely occur with products that have a long regulatory history as this implies a relative high amount of additional work. When submitting changes to module 3, it will be expected that in most cases the full section Drug Substance and/or Drug Product will be submitted (option 4). Exceptions (when such submissions will not be of added value) should be justified in the cover letter.
    • Guidance for Industry Version 1.2 22/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 Furthermore all the documents of module 1 relevant to the Marketing Authorisation are to be included into the baseline submission, therefore Module 1 should contain as a minimum and where applicable:  Cover Letter of the stand alone baseline submission or of the concommitent variation  Form Application for Marketing Authorisation/Variation Annexes - Forms  Form Full Declaration  Form Manufacturer Information  Form Status Marketing Authorisations Abroad  Form Variations Requiring Notification  Form Application for Renewal of Marketing Authorisation  Form Human Blood Components  Form Substances of Animal and Human Origin  Form Pharmaceutical Information for Parenteral Preparations  Form Co-Marketing Confirmation  Form Import According to Paragraph 14 Section 2 TPA  Form Safety Changes to Product Information  Form Change of Marketing Authorisation Holder  Form Paragraph 13  Form PSUR for Human Medicinal Products  Form Declaration Radiopharmaceuticals  Other Forms Annexes - Documents on Drug Product Quality  DMF Letter of Access  Ph. Eur. Certificate of Suitability for Active Substance  Ph. Eur. Certificate of Suitability for TSE  EMA Certificate for Plasma Master File (PMF)  EMA Certificate for Vaccine Antigen Master File (VAMF) Annexes - Manufacturing  GMP Certificate or Other GMP Documents  Documentation Concerning Manufacturing Authorisation  Complete Manufacturing Information with Flow Chart Annexes - Others  Information for Professionals  Patient Information  Packaging Information Information Relating to Pharmacovigilance  Pharmacovigilance System  Risk Management System Others  Additional Information
    • Guidance for Industry Version 1.2 23/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 7 Submission of PSURs and E2E / RMP Updates in eCTD Format Applicants who choose to file a PSUR and or an E2E / RMP Update submission in eCTD format must comply with the following requirements: 7.1 PSUR 7.1.1 Application type “PSUR” -> please fill in the Form PSUR for Human Medicinal Products Use this application type when submitted as part of the PSUR Program based on VAM (Ordinance of Medicinal Products) and TPA (Therapeutic Products Act)  Art. 34 VAM (authorization received within the last 5 years)  Art. 34 reference Art. 17 paragraph 2 VAM (major changes within the last 5 years)  Art. 16 paragraph 1 TPA (commitments) Product Information Variation (VAR-PI) based on a PSUR submitted as part of the PSUR Program When a PSUR, submitted as part of the PSUR Program, serves also as a supporting document for a Product Information Variation, two sequences are required, one for “PSUR” and one for “VAR-PI”. Indicate in the Cover Letter and in both forms, the “PSUR” and the “Application for Marketing Authorisation and Variation Form” that two associated sequences have been submitted. 7.1.2 Application type “Supplemental Information“  Use this application type when submitted outside of the PSUR Program (non-VAM and non-TPA based PSUR) and for other reasons such as: requested by Swissmedic, to inform about a safety signal, submission of a new version of the E2E / RMP (see section 7.2).  Mention the reason for submission in the Cover Letter. 7.2 E2E / RMP Update 7.2.1 Application type “PSUR” if submitted as part of the regular PSUR Program  Submit only when there are relevant changes to the previous version.  Mention the differences to the previous version in the PSUR Form. 7.2.2 Application type “Supplemental Information” if not submitted as part of the regular PSUR Program  Mention the reason for submission in the Cover Letter.
    • Guidance for Industry Version 1.2 7.3 Structure for a PSUR submission as part of the regular PSUR Program Module / Requested Documents Comments Operator 1.0 Cover Letter  operator always new 1.2.2.16 Form PSUR  operator always  also as working document requested (word file outside the eCTD structure)  new design created for eCTD and paper submission new 1.2.5.1 Comparison EU- SmPC vs. CH-FI  operator always new 1.2.5.2 CCDS  operator first version / eCTD submission  operator if changes from previous version  leave section empty if no changes and mention in the PSUR-Form “Comment Field” that there are no changes new replace 1.3.4 Information for Professionals other Countries (EU SmPC)  operator first version / eCTD submission  operator if changes from previous version  leave section empty if no changes and mention in the PSUR-Form “Comment Field” that there are no changes new replace 1.8.2 E2E / RMP Update  operator if changes from previous version  operator also for attachments  main document should be listed first if possible  leave section empty if no relevant changes replace new or replace 5.3.6 PSUR  operator always new 24/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12
    • Guidance for Industry Version 1.2 25/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 8 Test eSubmissions In order to prevent technical errors in eCTD applications, Swissmedic encourages the submission of test eCTDs, particularly if the applicant has limited experience of submitting eCTDs. In a test submission, areas of technical concern can be tested. The test submission process at Swissmedic is an informal process, intended to accord pragmatic assistance to the applicant. A test eCTD can be provided on CD or DVD at any time up to 3 weeks prior to the filing date. It is recommended to do so as early as possible, in particular if the applicant has limited / no experience with eCTD submission. Swissmedic cannot guarantee that a test submission will be processed if provided within 3 weeks prior the submission filing date. The test eCTD should be as representative as possible of the final eCTD submission, particularly in terms of structure, envelope and metadata used. The individual files of the test submission will not be reviewed, so “dummy” files can be submitted. The hard media with the test submission should be appropriately packaged to prevent damage during transport, and the CDs/DVDs should be appropriately labeled in order to ensure easy identification of the test submission and its purpose. Here, the applicant name, invented name if known, INN and type of application and “TEST eCTD” should suffice, as well as any information relating to the number of media units and submissions contained therein for organization if appropriate. The root folder name of the test eCTD should include the word “Test”. The eCTD should be further accompanied by a brief paper cover letter explaining the purpose of the test submission, and indicating applicant contact details for feedback on the eCTD. The cover letter should state the expected filing date for the true submission. Two copies of the test eCTD should be provided on two sets of CDs/DVDs, in order to be able to overcome hard media damages and corruptions. The second copy can also be used to test CD/DVD writer/publishing compatibility with Swissmedic CD/DVD reader hardware if different versions are under consideration by the applicant. (See also the Swiss eCTD Validation Criteria about sending a validation report.) The test eCTD will be checked by a technical sector of Swissmedic. Information will not be passed on to case management or reviewers for the product unless there are specific questions arising that relate to business requirements or business issues with the eCTD. The test eCTD is therefore not subject to a content validation.The tests are exclusively technical. The test eCTD will be checked using the Swissmedic’s eCTD review system and the submission will be viewed in order to ascertain that the presentation of the dossier is as expected, that documents can be accessed, and that correct use of structure and metadata has been made. Hyperlinks, if provided in documents, may be tested if functioning. Particular aspects of the eCTD, if highlighted by the applicant may also be checked. Swissmedic will make every effort to reply to the applicant within 2 weeks of receipt of the test eCTD. The applicant will be provided with a copy of the technical validation report, and any particular issues will be highlighted along with a recommendation for resolution. The applicant will be advised to liaise with the case manager if further business issues need to be clarified. The hard media containing the test submission will be discarded after testing.
    • Guidance for Industry Version 1.2 26/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 The process of submission of test eCTDs can be iterative, if considered necessary to ensure adequate resolution of any issues reported. Even if the test submission has been tested successfully and the test submission contains the true data for application, test submissions can not stay with Swissmedic to be accepted for review. 9 Shipment The paper copies and the hard media should be submitted jointly. Two copies of the eCTD on DVD/CD should be submitted to Swissmedic at the following address: Swissmedic Swiss Agency for Therapeutic Products Hallerstrasse 7 For the attention of: eCTD P.O. Box CH-3000 Bern 9 Switzerland
    • Guidance for Industry Version 1.2 27/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 10 Appendices Appendix 1: eCTD Reference Documents Swissmedic reference documents Guidance for Industry on Providing Regulatory Information in eCTD Format Swiss Module 1 Specification for eCTD Swiss eCTD Validation Criteria Questions and Answers to Swissmedics eCTD implementation ICH ICH: http://www.ich.org ICH electronic Common Technical Document (eCTD): http://estri.ich.org ICH Specification 3.2 (Modules 2 - 5) (Notice to Applicants Vol 2B): http://estri.ich.org/eCTD/index.htm ICH Q&As: http://estri.ich.org/ectd ICH M4 Granularity: http://www.ich.org/LOB/media/MEDIA554.pdf ICH ETICS M2 Project: http://www.etics.us ICH M2 (Q&A or Change Request Form): http://estri.org/eCTD/eCTD_Change_Request_Form.rtf eSubmission Links of EU Health Authorities NTA-TIGes Interlinking (Q&A and Change Request Form): http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/b/ectd_12- 2006/crform.doc Latest agreed EU Telematics EU eCTD Change Request/Q&A Tracking Table: http://esubmission.ema.europa.eu/EU_Change_Request_Q&A_Tracking_Table%20v1.1 7.xls EMA Q&A regarding eSubmission: http://www.ema.europa.eu/htms/human/resub/q24.htm EU M1 v1.3 Transition Guidance : http://esubmission.ema.europa.eu/EU%20M1%20v1.3%20Transition%20Guidance%20- %20FINAL%20.doc Question and Answer document relating to practical and technical aspects of EMA eCTD Implementation for the Centralised Procedure: http://www.ema.europa.eu/pdfs/human/regaffair/63391908en.pdf Guidance for Industry on Providing Regulatory Information in Electronic Format: eCTD electronic Submissions http://esubmission.ema.europa.eu/doc/eCTD%20Guidance%20Document%201.0%20FI NAL%20FOR%20PUBLICATION.pdf
    • Guidance for Industry Version 1.2 28/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 Appendix 2: Swissmedic types of applications This appendix describes the list of the application types according to the Swissmedic process map and their acceptability in eCTD format. For any type of dossier not listed in the table please contact Swissmedic before submission. Also, should an urgent update to an application (e.g. urgent safety update) be needed before the approval of sequence 0000, please contact Swissmedic before submission. ID Type of Applications Acceptability ZL101 New applications: NAS: New Active Substance NGF: New Galenic Form NKO: New Combination BWS: Known Active Substance NA Generikum: Generics IE: New Indication NDE: New Dosage Recommendation NDO: New Dosage Strength Accepted Step 3: Paragraph 13 TPA, from 1 January 2011, see standalone Guidance on applications according to Paragraph 13 TPA for eCTD applications ZL102 Application for Orphan Drug Status/MUMS MUMS not allowed. For Orphan Drug Status Application only if submitted simultaneously with ZL101 ZL103 Notification procedure for complementary medicine Not allowed AA103_20 PSUR Step 3: 1 January 2011 ZL104 Application for Fast Track Procedure Not allowed ZL105 Meetings with applicants during marketing authorisation procedure Not allowed ZL106 Parallel Import Step 3: 1 January 2011 ZL107 Application for 5 years Data Protection Step 3: 1 January 2011 ZL108 Co-marketing Step 3: 1 January 2011 ZL109 Temporary Authorisation Step 3: 1 January 2011 ZL110 New application for inactivation procedure (manufacturer) Not allowed ZL111 New application for inactivation procedure (centers) Not allowed ZL112 Notification procedure for veterinary medicinal products Not allowed ZL113 Recognition of a product monograph Not allowed ZL201 Prolongation, renouncement of prolongation Step 3: 1 January 2011 ZL202 Renouncement of authorised medicinal products Step 3: 1 January 2011
    • Guidance for Industry Version 1.2 29/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 ID Type of Applications Acceptability ZL301 Variations requiring a notification procedure Accepted ZL302 Variations requiring authorisation incl. scientific review Accepted ZL303 Variations requiring authorisation without scientific review Accepted ZL304 Variations requiring authorisation of the product information (SmPC, patient information) Accepted ZL305 Notification procedures for sample packages Step 3: 1 January 2011 In line with the principle of “once eCTD – always eCTD” applications which are subsequent to an initial Marketing Authorisation Application will be accepted as soon as the initial Marketing Authorisation Application (ZL101) is approved, for ZL107 as soon as needed.
    • Guidance for Industry Version 1.2 30/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 Appendix 3: List of documents requested additionally in paper format Number of copies Name of document in English German document designation/code French document designation/code 1 Cover Letter Begleitbrief Lettre d’accompagnement 1 Form Application for Marketing Authorisation and Variation Formular Gesuch Zulassung/Änderung- Formulaire Demande d'autorisation / de modification 1 Form Full Declaration Formular Volldeklaration Formulaire Déclaration complète 1 Form Manufacturer Information Formular Herstellerangaben Formulaire Renseignements concernant les fabricants 1 Form Status Marketing Authorisations Abroad Formular Status Zulassungsgesuche im Ausland Formulaire Status des demandes d'autorisation déposées à l'étranger 1 Form Variations Requiring Authorisation (Quality) Formular Genehmigungspflichtige Änderung Qualität. Formulaire Modification soumise à approbation relative à la qualité 2 Form Variations Requiring Notification Formular Meldepflichtige Änderungen Formulaire Modification soumise à l'obligation d'annoncer 1 Form Application for Renewal of Marketing Authorisation Formular Gesuch Verlängerung Zulassung Formulaire_Demande de prolongation de l'autorisation 1 Form Human Blood Components Formular Humane Blutbestandteile Formulaire Composants sanguins humains 1 Form Substances of Animal and Human Origin Formular Stoffe tierischen und humanen Ursprungs Formulaire Produits d'origine animale ou humaine 1 Form Pharmaceutical Information for Parenteral Preparations Formular Pharmazeutische Angaben FI und PI betreffend Parenteralia Formulaire Renseignements pharmaceutiques – Informations professionnelle et destinée aux patients – concernant les préparations parentérales 1 Form Co-Marketing Confirmation Bestätigung Co-Marketing Attestation de Co-Marketing 1 Form Import According to Paragraph 14 Section 2 TPA Einfuhr eines Arzneimittels nach Art. 14, Abs. 2 HMG (Parallelimport) Importation d'un médicament selon l'art 14, al. 2 LPTh 1 Form Safety Changes to Product Information Formular Sicherheitsrelevante Änderungen der Arzneimittelinformation Formulaire pour les demandes de modification de l’information
    • Guidance for Industry Version 1.2 31/31 Swissmedic · Hallerstrasse 7 · CH-3000 Bern 9 · www.swissmedic.ch · Tel. +41 31 322 02 11 · Fax +41 31 322 02 12 Number of copies Name of document in English German document designation/code French document designation/code 1 Form Change of Marketing Authorisation Holder Formular Übertragung Zulassung Formulaire Transfert de l’autorisation / changement de raison sociale ou de domicile 1 Checklist Content Validation eCTD Checkliste Formale Kontrolle Zulassungsgesuche eCTD Checkliste Contrôle formel eCTD 1 Checklist Content Validation eCTD Paragraph 13 TPA must be filed as Checklist Paragraph 13 (Content Validation) Checkliste Formale Kontrolle Art. 13 HMG eCTD muss unter Checkliste Art. 13 abgelegt werden Checkliste Contrôle formel eCTD Art. 13 LPTh doit être classer comme Checkliste Contrôle formel Art. 13 LPTh 1 Form PSUR for Human Medicinal Products Formular PSURs für Humanarzneimittel Formulaire PSUR pour les médicaments à usage humain 1 Form Declaration Radiopharmaceuticals Formular Deklaration Radiopharmazeutika Formulaire Déclaration des produits radiopharmaceutiques 1 DMF Letter of Access DMF Letter of Access Lettre d’accès au DMF 1 GMP Certificate and Other GMP Documents GMP-Zertifikat oder andere GMP Dokumente Certificat GMP et autres documents GMP 1 Documentation Concerning Manufacturing Authorisation Dokumentation Herstellungsbewilligung Documentation Autorisation de fabrication 1 Form Confirmation Substances from GMO Formular Bestätigung Stoffe aus GVO Formulaire Attestation substances à base d’OGM 1 Form DMF for First Authorisation and Variations Formular DMF für Erstzulassung / Änderung Formulaire DMF première autorisation / modification 1 Form Information on Product Quality (Paragraph 13 TPA) Formular Informationen zur Qualität bei Antrag Art. 13 HMG Formulaire Demandes selon art. 13 LPTh : informations sur la qualité 5 Information for Professionals Fachinformation Information professionnelle 5 Patient Information Patienteninformation Information pour les patients 5 Packaging Information Packmaterial (Faltschachtel, Etikette, Blister) Eléments d’emballage 1 Form Technical Validation eCTD (Form is not available in German) (Form is not available in French) [End of document]