The Electronic Regulatory Submission


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The Electronic Regulatory Submission

  1. 1. Development and eCTD submission Process & Contents
  2. 2. Rajeev Kashyap TIPT
  3. 3. Rajeev Kashyap TIPT Time Personnel Methods Materials Environment Communication Initiating Process Planning Executing
  4. 4. Cost cutting &Processing Time Rajeev Kashyap TIPT
  5. 5. <ul><li>The XML eCTD DTD describes the hierarchical structure according to the CTD as defined by the ICH M4 Expert Working Group. </li></ul><ul><li>The XML eCTD instance covers the entire submission including all hierarchical levels and includes references to each individual file. </li></ul><ul><li>The submission should include a Style sheet that supports presentation of the XML </li></ul>Rajeev Kashyap TIPT
  6. 6. <ul><li>Directory Structure : A structure of directory and files </li></ul><ul><li>XML eCTD: Intention to have links from leaf element. </li></ul><ul><li>eCTD empty template included in ICH Web site be available for 50 years in PDF –XML(Extensible mark-up language) and the graphics in JPEG, PNG,SVG, GIF format. </li></ul><ul><li>eCTD should have checksums for each file. </li></ul><ul><li>Contents file . </li></ul>Rajeev Kashyap TIPT
  7. 7. <ul><li>The number of eSubmissions to the FDA now over 60,000 . </li></ul><ul><li>Regulatory agencies in the U.S., EU, Japan, and Canada in the areas of eSubmission strategy, document and records management, </li></ul><ul><li>Compliance software integration. </li></ul><ul><li>Efficiency </li></ul><ul><li>Problems with paper </li></ul><ul><li>Industry and modern trends </li></ul><ul><li>Competitive edge </li></ul><ul><li>FDA “encouragement” </li></ul>Rajeev Kashyap TIPT
  8. 8. <ul><li>New Drug Applications (NDAs) </li></ul><ul><li>Supplemental NDAs (sNDAs) </li></ul><ul><li>Investigational New Drug Exemptions (INDs) </li></ul><ul><li>Clinical Trial Authorization (CTAs) filed in EU </li></ul>Rajeev Kashyap TIPT
  9. 9. <ul><li>Electronic versions of Agency-Required Regulatory Submissions </li></ul><ul><ul><li>IND, NDA, BLA, Correspondences, Safety Reports </li></ul></ul><ul><ul><li>CTA - other marketing apps… </li></ul></ul><ul><ul><li>eCTD vs. hybrid esub </li></ul></ul><ul><ul><li>Format: PDF, XML, SAS, MSWord, JPG </li></ul></ul>Rajeev Kashyap TIPT
  10. 10. <ul><li>ICH - guidelines </li></ul><ul><li>The eCTD has five modules </li></ul><ul><li>1 Administrative Information and Prescribing Information </li></ul><ul><li>2 Common Technical Document Summaries </li></ul><ul><li>3 Quality </li></ul><ul><li>4 Nonclinical Study Reports </li></ul><ul><li>5 Clinical Study Reports </li></ul><ul><li>There are two categories of modules: </li></ul><ul><li>Regional module: 1 (different for each region; i.e., country) </li></ul><ul><li>Common modules: 2-5 (common to all the regions) </li></ul>Rajeev Kashyap TIPT
  11. 11. <ul><li>Not part of the eCTD </li></ul><ul><li>Regional Administrative information </li></ul>Rajeev Kashyap TIPT
  12. 12. Rajeev Kashyap TIPT
  13. 13. <ul><li>Regional guidance will provide the specific instructions on how to provide the administrative forms and detailed prescribing information. </li></ul><ul><li>There will be local requirements for both the content and electronic component of module 1. </li></ul><ul><li>The eCTD backbone was developed to enable the transfer of the regional information included in a regulatory dossier </li></ul><ul><li>A description of the submission including appropriate regulatory information. </li></ul><ul><li>A listing of the sections of the submission filed as paper, electronic, or both paper and electronic . </li></ul><ul><li>A description of the electronic submission including type and number of electronic media, </li></ul><ul><li>Approximate size of the submission, and if appropriate, characteristics concerning the media (e.g.,format used for DLT tapes) . </li></ul><ul><li>A statement that the submission is virus free with a description of the software used. </li></ul><ul><li>The regulatory and information technology points of contact for the submission </li></ul>
  14. 14. <ul><li>Administrative Information & </li></ul><ul><li>Prescribing Information. </li></ul><ul><li>Cover Letter </li></ul><ul><li>Form 356h </li></ul><ul><li>labelling information (Draft) </li></ul><ul><li>Cartoon and Containers Labels </li></ul><ul><li>Clinical Trials label. </li></ul><ul><li>Pack inserts </li></ul><ul><li>Investigator Boucher </li></ul><ul><li>Financial Disclosure </li></ul><ul><li>Exclusivity Certificate </li></ul><ul><li>Patent certificate </li></ul><ul><li>Risk management plan </li></ul>
  15. 15. Rajeev Kashyap TIPT
  16. 16. Rajeev Kashyap TIPT
  17. 17. <ul><li>A document can be equated to a file for an electronic submission . </li></ul><ul><li>A document is defined for a paper submission as a set of pages, numbered sequentially and divided from other documents by a tab </li></ul>Rajeev Kashyap TIPT
  18. 18. <ul><li>The granularity of the paper and electronic submissions should be equivalent, although if a paper submission is updated to be an electronic submission, some changes in granularity could be introduced to facilitate on-going lifecycle management. </li></ul><ul><li>Optionality of granularity for the Quality Overall Summary is provided in order to accommodate different levels of complexity of products. The applicant can choose the level at which the QOS is managed. </li></ul><ul><li>One document should be submitted for each drug substance </li></ul><ul><li>For a drug product supplied with reconstitution diluent(s), the information on the diluent(s) should be provided in a separate part “P” document </li></ul><ul><li>One document for each indication should be submitted, although closely related indications can be within a single document </li></ul>Rajeev Kashyap TIPT
  19. 19. <ul><li><m3-2-s-2-manufacture> </li></ul><ul><li><m3-2-s-2-1-manufacturer> </li></ul><ul><li><leaf ID=&quot;xxx&quot; operation = &quot;new&quot; xlink:type = &quot;simple“ checksum-type=&quot;md5&quot; checksum= &quot;xxx&quot; </li></ul><ul><li>xlink:href = &quot;m3/32-body-data/32s-drug-sub/xxx/32s2-manuf/xxx&quot; application-version = &quot;xxx&quot;> </li></ul><ul><li><title>xxx</title> </li></ul><ul><li></leaf> </li></ul><ul><li></m3-2-s-2-1-manufacturer> </li></ul>Rajeev Kashyap TIPT
  20. 20. <ul><li>Building blocks: </li></ul><ul><ul><li>PDF files for text* </li></ul></ul><ul><ul><li>MD5 transport files for checksum data* </li></ul></ul><ul><li>Connected through XML backbone </li></ul><ul><ul><li>Looks like a web page </li></ul></ul><ul><ul><li>Viewing </li></ul></ul><ul><ul><li>Links and bookmarks </li></ul></ul><ul><ul><li>Search keywords, metadata </li></ul></ul><ul><ul><li>Managing lifecycle (Append, Replace, Delete) </li></ul></ul>Rajeev Kashyap TIPT
  21. 21. <ul><ul><li>Document Storage and Transfer </li></ul></ul><ul><ul><ul><li>EDMS v/s file system </li></ul></ul></ul><ul><ul><ul><li>Balance version control, security and flexibility </li></ul></ul></ul><ul><ul><li>Acrobat </li></ul></ul><ul><ul><ul><li>Conversion from MSWord </li></ul></ul></ul><ul><ul><ul><li>PDF version compatibility </li></ul></ul></ul><ul><ul><li>Plug-in Tools </li></ul></ul><ul><ul><ul><li>Publishing PDF docs </li></ul></ul></ul><ul><li>Bookmarks, links, … </li></ul><ul><li>In addition to esub tools: </li></ul><ul><li>eCTD Compiler Tool </li></ul><ul><ul><li>Major IT project! </li></ul></ul><ul><ul><li>Validation/upgrade </li></ul></ul><ul><ul><li>Migration </li></ul></ul><ul><ul><li>Implementation </li></ul></ul><ul><ul><li>External Links </li></ul></ul>Rajeev Kashyap TIPT
  22. 22. <ul><li>Regulatory submission strategy and technology </li></ul><ul><li>Electronic and paper submissions to Regulatory Agencies for drug registration </li></ul><ul><li>Template for authoring regulatory docs </li></ul><ul><li>eCTD, hybrid electronic submissions </li></ul><ul><li>Liaise with FDA on Esub requirements </li></ul><ul><li>SPL - Structured Product Labeling </li></ul><ul><li>Gateway implementation </li></ul><ul><li>Fill able forms + Digital Sigs: 356h, 1571… </li></ul><ul><li>Submission lifecycle tracking + archiving </li></ul>Rajeev Kashyap TIPT
  23. 23. <ul><li>Drive electronic submission acceptance and adoption within company </li></ul><ul><li>Lead software implementation projects </li></ul><ul><li>Cross functional training and awareness of Esub initiatives </li></ul><ul><li>Esub guidance and specification interpretation </li></ul><ul><li>Keep Upper Management informed of: </li></ul><ul><ul><li>new regulatory submission requirements </li></ul></ul><ul><ul><li>how to adopt new technology and processes to sustain competitive advantage </li></ul></ul>Rajeev Kashyap TIPT
  24. 24. PAPER V/S E SUB COMPARISON <ul><li>E-publishing software </li></ul><ul><li>Authoring templates - MSWord </li></ul><ul><li>Volumization </li></ul><ul><li>Volume TOC creation </li></ul><ul><li>Overlays: page stamps, master headers/footer info </li></ul><ul><li>Print: multiple copies </li></ul><ul><li>E-publishing software </li></ul><ul><li>Still based on e-templates </li></ul><ul><li>Document info, descriptive metadata* </li></ul><ul><li>PDF Table of contents creation* </li></ul><ul><li>Navigation: Bookmarks, links (automation key) </li></ul>Rajeev Kashyap TIPT
  25. 25. <ul><li>Clinical QC √-list </li></ul><ul><li>Medical Writing √-list </li></ul><ul><li>QA reports </li></ul><ul><li>Publishing work practices </li></ul><ul><li>CLINICAL SUMMARY REPORTS Publishing work practice </li></ul><ul><li>CSR Appendix √-list </li></ul><ul><li>Electronic PDF √-list </li></ul><ul><li>Guide for eSub ready Docs </li></ul><ul><li>Scanned Document √-list </li></ul><ul><li>eQC √-list </li></ul>Rajeev Kashyap TIPT
  26. 26. <ul><ul><li>eCTD Taskforce: Reg Ops, Reg Affairs, Medical Writing, and other functional group representation </li></ul></ul><ul><ul><li>Company-wide “awareness” </li></ul></ul><ul><ul><ul><li>Presentations at Project Team meetings </li></ul></ul></ul><ul><ul><li>Templates and Training </li></ul></ul><ul><li>Process Agreements </li></ul><ul><li>eCTD Task force </li></ul><ul><li>Med Writing – Reg. Ops – Data Mgt – other functional group reps </li></ul><ul><li>File Transfer </li></ul><ul><ul><li>EDMS </li></ul></ul><ul><ul><li>File share </li></ul></ul><ul><ul><li>eRooms </li></ul></ul><ul><ul><li>eArchival </li></ul></ul>Rajeev Kashyap TIPT
  28. 28. <ul><li>Electronic Submissions Gateway </li></ul><ul><ul><li>created as required by [ The Prescription Drug User Fee Act ] PDUFA IV legislation as the single point of entry for the receipt and processing of electronic submissions to the FDA </li></ul></ul><ul><li>PDUFA enable FDA to accelerate its drug evaluation process without compromising review quality.    </li></ul>Rajeev Kashyap TIPT
  29. 29. <ul><ul><li>New Drug Applications (NDAs) CDER Central Document Room: FDA/Center for Drug Evaluation and Research (CDER) Central Document Room (CDR) 5901-B Ammendale Road Beltsville, MD 20705-1266 </li></ul></ul><ul><ul><li>Abbreviated New Drug Applications (ANDAs) Office of Generic Drugs 7500 Standish Place Rockville, MD 20855 </li></ul></ul>Rajeev Kashyap TIPT
  30. 30. Rajeev Kashyap TIPT
  31. 31. <ul><li>ICH Website: </li></ul><ul><li>SPL Resources: </li></ul><ul><li>CPage: Submit electronically via the Gateway: CDER's eCTD Validation Criteria: </li></ul><ul><li>Daily Med Approved Labels: </li></ul><ul><li> </li></ul><ul><li>CDISC Standards: </li></ul>Rajeev Kashyap TIPT
  32. 32. <ul><li>? </li></ul>Rajeev Kashyap TIPT