©2014 Factorytalk Co., Ltd. Proprietary and Confidential eCTD Specification 17 July 2014

( 2 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential ACTD ASEAN established the ASEAN Common Technical Document (ACTD) to create harmonized requirements and a common format for all submissions of dossiers in the ASEAN countries. The ACTD is based on the European standard (CTD), CTD format is required for the registration of all drug products into EMEA regulated countries. Contents of Module 2 in CTD were separate in to ACTD Part 2,3,4 as paper management during review process is easier. TOCs aren’t required anymore in eCTD

( 3 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential eCTD Module 1 Regional Admin Information Module 3 Quality Module 4 Nonclinical Study Reports Module 5 Clinical Study Reports Quality Overall Summary Nonclinical Summary Nonclinical Overview Clinical Summary Clinical Overview Module 2 NOT Part of the CTD The CTD ICH M4 ACTD Part 1 ACTD Part 2 ACTD Part 3 ACTD Part 4 ACTD

( 4 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Business Protocol Prepare Submission Application Prepare Submission Application eSubmission Identifier from THAI FDA website Prepare the cover letter and validation report Prepare the cover letter and validation report Delivery of the eCTD Application at FDA (CD) FDA : Feedback on Validation of Application FDA : Start review process FDA : Start review process

( 5 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Regional Content Module 1 administrative and prescribing information -The content and numbering of Module 1 for Thailand is modelled after the EU Module 1 content as described in the 2008 version of the EU Notice to Applicants. Additional documents specifically required by Thailand not covered by the EU structure is describe in 1.A Additional Data of TH Module 1 and Regional Specification Modules 2 to 5 -No change from ICH eCTD Specification. Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 6 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Handling of Empty or Missing eCTD Sections For new applications, including generic applications, detailed statements justifying the absence of data or specific CTD sections should be provided in the relevant Quality Overall Summary and/or Nonclinical/Clinical Overviews e.g. Module 2.3, 2.4, or 2.5. For a generic application, there is no need to provide a justification for content that is typically absent. Note that placeholder documents highlighting no relevant content should not be placed in the eCTD structure. Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 7 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Bookmarks, TOCs, and Hyperlinks Bookmarks and/or TOCs make the review more efficient. The FDA recommends that documents with more than five pages and with multiple sections should provide a Table of Contents, and/or if appropriate, a Table of Tables, Table of Figures, etc. on the first page of the document. Hyperlinks are recommended when they would aid the evaluation in ways not already possible through the use of the eCTD index.xml and document navigation aids. Applicants should consider when creating cross document hyperlinks that they can cause confusion later in lifecycle and therefore be distracting for an efficient review. Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 8 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential File Reuse The FDA accepts and encourages applicants to make active use of file reuse. Applicants should not submit the same document multiple times. File reuse should be used when -a file is submitted multiple times within one sequence, -a file already submitted in an earlier sequence is being referenced again, -or if a file submitted in another application is being referenced in a new application. Please note that the FDA is implementing a flat repository structure to make cross application referencing possible. -Links to content provided in other applications simply need to be directed out of the current application structure and into the structure of the corresponding application. -All application will be stored using the eSubmission Identifier to make cross referencing easily predictable and possible. Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 9 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Structure Naming conventions for the content files are irrelevant for electronic review All content must be referenced by the appropriate XML files for efficient navigation. Applicants should concentrate on providing precise but informative leaf titles to aid reviewers. Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 10 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential eSubmission Identifier A request for an eSubmission identifier should made via website (THAI FDA e-logistic data base). The request will require the following information: -Licensee Number -Description of Application. -Dosage Form -INN or Generic Name -Strength -WHO ATC Code -Sequence Type -Application form (CPP) Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 11 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential eSubmission Identifier The eSubmission Identifier will be issued within 10 days of application. The Applicant must check on the THAI FDA online service for a response informing them of their eSubmission Identifier. After receiving the identifier, the Applicant must then make an appointment for submission within 30 days. Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 12 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Validation Criteria No major new or unusual validation criteria developed from EU eCTD V3.2 Other regions were analysed, compared and adopted if suitable Detail validation criteria can be found at TH Regional Specification and Validation Criteria Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 13 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Items worth noting Validation Criteria Files and Folders -There are no naming conventions being validated ICH Backbone -File Reuse - Information is collected about references outside the application and sequence as well as multiple references to a file within a sequence TH Regional -File Reuse -Cover Letter must be New -Information is collected when Application Form is not New Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 14 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Validation Tools Most vendors offer free basic versions of their validation tools No excuses for submitting applications that do not pass technical validation Make sure you validate on the media being submitted Validation should be limited to criteria specified by the FDA -Some vendors provide extended profiles, these should not be provided with the application List of validation tools will be provided on the eSubmission Website as vendors provide evidence that they can sufficiently validate the FDA requirements Current free version of validation tool being used by the FDA can be found at: - (Link also provided on FDA eSubmission webpage) Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 15 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Business Protocol for Submitting eCTD Expected Structure of Submitted Media and Media Formats Expected structure of submitted media -Content should be submitted in an application folder named after the eSubmission identifier. -The sequence folder and its contents should be placed in this application folder. -Large applications must be split and submitted on multiple items e.g. DVDs -The overall folder structure should be included on each media so that content can be easily merged Media formats -The media formats acceptable when submitting an eCTD are: o CD-R, DVD-RAM, DVD+R/-R, -Ensure that you do not use: o double-sided discs, rewritable discs or compressed or zipped files (except for validation reports). Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 16 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Delivery of the eCTD Application The Applicant will need to make an appointment through and deliver the application personally at the Division of Policy System Development. The eCTD will be validated and imported into the THAI FDA Review System together with the applicant. Once accepted and submitted, the applicant will be given back their media to keep. Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 17 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Application feedback THAI FDA will inform applicants if there are problems experienced during the upload of an eCTD sequence. Confirmation of validation document will be issue during appointment. Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 18 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Start Review Process Initial Content Screening Process Initial Content Screening Process Evaluation Process Evaluation Process Administration Process (include LoQ ) Administration Process (include LoQ ) Issue Registration Certificate Issue Registration Certificate Prepare Application eSubmission Identifier Validation report Delivery the application Application feedback Reviewing process

( 19 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Implementation of eCTD *2002 Implementation Status of Submission System, Thomson Reuters

( 20 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Implementation of eSubmission *2002 Implementation Status of Submission System, Thomson Reuters

( 21 ) ©2014 Factorytalk Co., Ltd. Proprietary and Confidential Thank you! Teerapong Cheepchol T: