A Regulatory application submitted via network or web directory to regulatory agencies..
IND, NDA, BLA, Correspondences, Safety Reports
MAA, CTA, 510ks, other marketing apps…
Special formats for creating documents
PDF, XML, SAS, MSWord, JPG
History of Electronic Submissions
1980s: Computer Assisted NDA (CANDA)
1995: CDER’s Submission Management and Review Tracking (SMART)
1997: CFR, Part 11 and PDUFA
1998 and 1999: Guidance Doc
2002: ICH Guidance M2
2006: Providing Electronic Submissions
NDA, IND, ANDA, DMF, 510K and PMA, etc
Amendment docs: Annual Reports, Labeling
Paperless, or near paperless submissions for faster marketing approval
Seamless, fast exchange of information within and across agency centers and external to the agency.
Elimination of duplication.
Rigorous records management and document control tracking, and archiving.
Electronic data Interchange (EDI) capability for data exchange.
Standards-based information repositories and data dictionaries
e-Submission vs eCTD
Important distinction: eSubmission ≠ eCTD, NeeS
The eCTD and NeeS is a particular type of electronic submission (NeeS applicable only for Europe)
Moving now towards the implementation of the eCTD as the specific format for electronic submission
Moving also towards the acceptance of electronic-only submissions, with eCTD the preferred standard. No paper requirement.
Electronic Common Technical Document
Method to electronically transfer product information and data collection of electronic files organized according to guidelines defining file format, folder/file naming conventions, document specifications, etc…..
Designed with considerations that facilitate
Life Cycle Management
Structure of eCTD
PDF files for text*
SAS transport files for data*
Connected through XML backbone
Looks like a web page
Links and bookmarks
Search keywords, metadata
Managing lifecycle (Append, Replace, Delete)
eCTD File Structure
eCTD File Structure Cont….
Example of XML Backbone
XML Mapping to Folders
Submission + knowledge management
Paper to Electronic (R) evolution
Paper submissions Electronic No Specialized Software Specialized E-publishing software's Overall and Module TOCs XML Back bone = TOC Printed Documents and various formats Electronic document, PDF Format Tabs for Navigation Bookmarks and Hyperlinks for Navigation More Physical Storage Space Less Physical Storage Space More time to pack and ship Less time to pack and ship ESG available Less efficient access and review More efficient access and review Difficult to review entire submission lifecycle Easy to review entire submission lifecycle
Paper/ e-submission cont….
This is a European-only specification
Initially developed as ‘interim’ as a lead in to eCTD–But will probably have a long duration of use
Should be an eCTD without the backbone but with PDF table(s) of content
NeeS/eCTD Comparison e-CTD EU-NeeS Format defined at ICH Harmonized European Format XML: <<backbone>> (TOC) - Lifecycle Management No XML ( Backbone / Envelope) No life Cycle Management PDF 1.4 Files (Including Application form and SPC) PDF 1.4, ICH ICH file Naming Conventions (Highly Recommended) File Naming Conventions Mandatory Hyperlinks One General TOC One Specific TOC per Module (m1-toc.pdf….) When Necessary MD5 Checksums No checksums
eCTD/NeeS Comparison Cont….
Encouraging the use of eCTD
Adapting to an international standard
Facilitating the management of MA- dossiers
Facilitating archiving of applications
Reduce the use of paper
Streamline the assessment process
Moving toward a more efficient system.
The Future of e-submissions
The FDA is steadily moving toward a fully electronic regulatory environment across ALL Divisions
As it works to achieve this goal, the FDA is seeking to help to develop and adopt more robust standards that promote increased review quality and organizational efficiency
The Future of eCTD will be RPS
Regulated Product Submissions
All FDA Divisions to be on the same platform for cost efficiencies ~2012
Based on XML similarities to eCTD
Standards predicted to converge with eCTD 4.0
RPS vs. eCTD RPS eCTD FDA harmonized Divisions Global Standard Not EU, Global Rigid folder structure Improved metadata and life cycle Difficult Lifecycle tracking Better DM integration Limited concept of Submissions/RU Single XML file Multiple XML files Undefined folder structure FDA Divisions not satisfied/unified Two way communication Metadata problems (can’t be corrected, poor life cycle issues) Hyperlink content to content Limited “relative” hyperlinks Same tools as eCTD eCTD 4.0 may converge with RPS
Relieves resource burdens related to paper distribution & storage