JSS College of Pharmacy Ooty, Tamil Nadu Sunday, April 24th , 2016 Understanding eCTD Fundamentals and creating your first eCTD Submission JSS College of Pharmacy Ooty, Tamil Nadu Sunday, April 24th , 2016

Objectives of the Workshop Understand the basics and terminologies of eCTD Demo on how to create FDA compliant dossiers using PharmaReadyTM eCTD Hands-on training on using PharmaReadyTM to create your first eCTD submission Q & A

G L O S S A R Y CTD – Common Technical Document ICH - International Conference on Harmonisation eCTD – Electronic Common Technical Document NeES – Non-eCTD Electronic Submission RIMS – Regulatory Information Management System GCC - Gulf Cooperation Council EMA - European Medicines Agency NCA - National Competent Authorities XML – eXtensible Markup Language XSL – eXtensible Stylesheet Language DTD – Document Type Definition

Agenda Overview of Regulatory Submissions & their Structure Overview of eCTD eCTD basics and terminology, eCTD architecture The XML backbone, File formats, Folder Structure Guidelines and Granularity, Study Tagging Files Checklists and Validation Criteria, Submission Ready Documents DTDs and Style sheets in the Util folder Dossier Preparation using PharmaReadyTM eCTD

Overview of Regulatory Submissions & Their Structure Understanding eCTD Fundamentals and creating your first eCTD Submission Overview of Regulatory Submissions & Their Structure

Regulatory Submissions Why? Need to gain approval from Regulatory agencies to market pharmaceutical drug products in their respective countries When? Innovator discovers a new molecule, Formulator knows of a patent expiration, API Manufacturer markets Drug Substance, Annual Reports, Amendments, etc. What? Administrative, prescription, manufacturing, CMC, quality, non-clinical and clinical study information How? Paper, Non-eCTD Electronic Submission (NeES), electronic Common Technical Document (eCTD) Whom? ICH Countries (US, EU, JP, CA) and Emerging Markets (TGA, MCC, Africa, South East Asia, Latin America, etc.)

Regulatory Submissions – contd. Phases

Regulatory Submissions – contd. Partial list of Regions and Countries for Regulatory Submissions GCC (Saudi Arabia, Oman, UAE, etc.) LEVANT (Turkey, Israel, Jordan, Lebanon, Palestine, Northern Cyprus, Syria) ASEAN (Malaysia, Singapore, Thailand) APAC (Australia, Brunei, Cambodia, etc.) EU (England, Austria, Belgium, etc.) CEE (Albania, Slovakia, Croatia, etc.) Some important MoH Websites: http://www.aseansec.org http://mccza.com/ http://www.sfda.gov.sa http://www.fda.gov http://www.jfda.jo http://www.ema.europa.eu/ema/ http://www.hc-sc.gc.ca https://www.swissmedic.ch/

CTD Structure CTD stands for Common Technical Document It is a logical ordering and organization of information It is a way of managing information at the document level 1. Came into effect in 2000 2. Adopted by ICH (International Conference on Harmonisation) 3. Organisation of the data into modules and nodes

Benefits of eCTD Financial Improved Application Review Process Printing and shipping costs are eliminated Application can be submitted in multiple countries with relatively minor changes Reduce review times, increase your response times to Agency requests, and ultimately lead to a faster approval Improved Application Review Process Most Agency reviewers prefer eCTD vs. paper Submissions can be uploaded to the Electronic Submissions Gateway (ESG) and are available to reviewers within hours Thanks to bookmarks and hyperlinks, a reviewer can easily jump to the paper you just cited, the table you just mentioned, or the validation report you just referenced Reviewers no longer have to search through countless paper volumes to determine what changes have been made to an application Convenience Multiple people can access the same documents at the same time – no more sharing paper volumes or making extra copies Agency employees can access the application remotely, allowing reviewers to continue their review regardless of their location Agency can audit the software used to create the eCTD submission during site inspections

Understanding eCTD Fundamentals and creating your first eCTD Submission Overview of eCTD

Overview of eCTD eCTD Terminology XML Backbone Application/Sequence Granularity Life cycle Checksum Href path Attribute LeafID Folder Util/Stylesheet/DTD STF

Fundamentals of eCTD – contd. eCTD Folder View eCTD Browser View

Fundamentals of eCTD – contd. Backbone XML View

Quick look into the Market Requirements Understanding eCTD Fundamentals and creating your first eCTD Submission Quick look into the Market Requirements

Electronic Submissions to US Application Types – FDA IND (Investigational New Drug Application) NDA (New Drug Application) ANDA (Abbreviated New Drug Application) DMF (Drug Master File) BLA (Biological license Application) FDA recommends sponsors to submit a pilot submission for technical evaluation Submission Types – FDA Original Application Amendment Re-submission Pre-submission Annual Report Establishment Description Supplement Efficacy Supplement Labeling Supplement CMC Supplement Other

Electronic Submissions to US – contd. Unique FDA Submission Requirements: Filled out Form 356h (ANDA) Annotated Label and Proposed Labeling Text Side by Side comparison of Labeling Text with RLD (ANDA) Signed, Executed Batch Records Study Tagging Files (STF) Clinical Study Reports (CSR) Case Report Form (CRF) Section 5.3.7 Case Report Forms no longer used Application number is always 6 digits All Drug Listings must be sent via Electronic Submission Gateway (ESG)

Document Publishing Standards All PDF documents must be between versions 1.4 and 1.7 All PDF documents that have more than 5 pages must have bookmarks and a table of contents that is linked to the respective pages. The bookmarks must generally match the table of contents The ZOOM levels for all the bookmarks and hyperlinks must be set to “Inherit Zoom” only The PDF document must be made searchable, or, should be OCRd if scanned and saved as PDF file The initial view should be set to “Bookmarks Panel and Page” if the PDF document has bookmarks. Else, should be set to “Page only” “Fast Web Access” and “Most Recent View” must always be enabled in all PDF documents

PharmaReadyTM Demo and Hands-On Training Understanding eCTD Fundamentals and creating your first eCTD Submission PharmaReadyTM Demo and Hands-On Training

PharmaReady Demo and Hands-on Training Creation of an ANDA Application for the Drug Product “WonderDrug” Creation of the Initial Sequence (0000) with relevant Submission type Loading of the Modules M1 to M5 Choosing the proper attributes for Drug Substance and Drug Product Adding Documents into the sequence using Drag and Drop Creation of Study Tagging Files Compiling and Validating the Sequence Creating Hyperlinks across documents for easier navigation Validating and Publishing the Sequence Creation of Amendment (sequence 0001) and Life Cycle Management of Documents Viewing the sequences 0000 and 0001 in the Consolidated Viewer – just as what is seen by FDA reviewers

Thank You Rajesh Prabu S.S. rajesh.prabu@navitas.net +91-9952758905