1	FDA Overview of the eCTD Guidance and Its Implementation E-submissions and Data Standards Updates March 4, 2004 Gary M Gensinger, MBA Director, Review Technology Staff Office of Information Management Center for Drug Evaluation and Research
2	Overview eCTD Guidance Changes from eNDA Guidance Continuation of eNDA Guidance Tools Resources for the Reviewer Resources for Industry Submissions 101 References
3	Where are we today… Working on becoming a standards based organization eCTD is just such a standard Part 11 electronic signatures Accepting IND, NDA, ANDA, BLA, DMF and related submissions in eCTD format Moving towards a paperless submission environment
4	Where are we going… Secure electronic transmission of eCTD submission Secure e-mail Gateway ELIPS & DailyMed Labeling Projects Structured Product Labeling Electronic submission in XML format
5	Electronic Submission Guidances Using eCTD Specifications Providing Regulatory Submissions in Electronic Format - Human Pharmaceutical Product Applications and Related Submissions Includes NDA, ANDA, BLA, IND, DMF and associated submissions Preferred Format for Submissions
6	Electronic Submissions Using eCTD Specifications Guidance Published August, 2003 eCTD Specifications FDA eCTD Table of Contents Headings and Hierarchy FDA Module 1 Specification FDA Modules 2 to 5 Specification Study Tagging File Specification Specifications Available On-Line http://www.fda.gov/cder/regulatory/ersr/default.htm Current eNDA/eANDA Guidances remain available as an alternative to the eCTD for NDA and ANDA only
7	eCTD Changes XML-based eCTD Backbone replaces PDF Tables of Content Backbone defines what can be submitted, not what must be submitted Increased document granularity in accordance with ICH eCTD agreements No requirement to submit technical sections or study reports in paper EVS processor performs rigid validation of backbone against DTD Requires strict adherence to specifications Do not add or modify leafs within the backbone Once a submission is sent in eCTD format all future submissions for the application should be in eCTD format Opportunity to use Part 11 Compliant Electronic Signatures
8	What doesn’t change Data files submitted in SAS XPORT format Documents submitted in PDF Format PDF should be text-based Understandable that aged legacy reports are scanned Contracts with CROs for current documents should require receipt of reports in text-based electronic format, e.g., MS Word or text-based PDF Draft labeling submitted in MS Word Office XP is being deployed Archival is temporal; format has little overall impact on archiving
9	Implementing the Guidance Initial Pilot Phase Contact CDER prior to generating submission Review process and make adjustments Accepting all submission types, e.g., IND, NDA, Amendments, Master Files, Annual Reports…
10	Making the Transition Convert to eCTD-based submissions at any time Starting sequence is sponsor decision Can start at 0000 or next available sequence Cannot repeat sequence numbers Serial number and sequence number are not the same Make move from paper-based to eCTD-based or eNDA-based to eCTD-based No requirement to resubmit material previously submitted in paper Reviewer training provided on a just-in-time basis Look for revised specifications for mapping to specifications Change is difficult for all Communication is key to success
11	eCTD Related Tools
12	Submission Processing Tool EVS Processing Tool Validates presence of required files Validates eCTD Backbone against DTD Validates location of content referenced in eCTD Backbone. Builds and maintains the comprehensive TOC Makes submission available for viewer & reviewer Adherence to the eCTD specification is critical
13	Submission Review Tools EVS Viewer Provides reviewers with direct access to submissions Provides submission based view of applications Provides a module based view of submissions Provides a “Cumulative Table of Contents” view of applications Provides download capability for off-line reviewing
14	Resources for the Reviewer Reviewer Training EST and EDAT JMP Just-In-Time Over-the-Shoulder Office of Information Management – Review Technology Pre-NDA Support OIM Attendance at pre-NDA Meetings Consultation on eSubmission Issues CTD and eCTD Subject Matter Experts
15	Resources for Industry CTD and eCTD Subject Matter Experts FDA is making EVS processing and review tools available to industry Download free from FDA web site Tools provided on an as-is basis No support from FDA will be provided 3^rd party developers are creating tools to support generation and validation of submission prior to FDA submission
16	Submissions 101
17	Office of New Drug Submissions Send All Original Applications to the Central Document Room Watch for announcement of change of address in Federal Register Send all amendment and supplement submissions containing electronic media or records to the Central Document Room Send all paper-only amendment or supplement submission to the Division Document Room
18	Office of Generic Drug Submissions Send submission to the Office of Generic Drugs
19	Just don’t ask… No paper unless required for original signatures No Word files or file formats not specified in the guidance No electronic submissions or records sent directly to a reviewer or project manager No electronic desk copies
20	References CDER Contact for information on eCTD and CTD submissions eSub@cder.fda.gov Electronic Regulatory Submissions and Review website http://www.fda.gov/cder/regulatory/ersr/default.htm International Conference on Harmonization http://www.ich.org