1. CTD Content Management
Michelle Herrera Foster, Ph.D.
Regulatory Affairs Consultant

2. Objectives
To present the use of the CTD/eCTD as a tool for content and document management throughout development to meet the goal of marketing approval and maintenance
To discuss meeting the needs of the development program with effective use of submission-ready documents, document management, and workflow processes.
Examples from Module 3 will be presented.

3. Regional Admin Information
ICH M4
NOT Part of the CTD
Regional Admin Information
Module 1
Module 2
Nonclinical Summary
Nonclinical Overview
The CTD
Clinical Summary
Clinical Overview
Quality Overall Summary
Module 4
Nonclinical Study Reports
Module 5
Clinical Study Reports
Module 3
Quality

4. The Common Technical Document (CTD)
Required in EU, Japan, and Canada for marketing applications
“Highly recommended” by FDA for NDA, BLA:
FDA follows ICH guidance
Good Guidance Practices (9/00) require that CTD not be mandatory
Required by CDER for eCTD submissions
Required in EU (IMPD) and Canada for investigational applications; accepted by FDA for IND

5. DRM Needs in CTD Preparation
Manage filing of information for ready accessibility by contributors, authors, and reviewers from IND to NDA
Develop shared databases in submission-ready templates, e.g. stability data
Agree on standards for terminology, product names, cross-references, etc.
Meet Quality standards and traceability to source documents; Quality Systems
Define content early to prepare and expand/update submission-ready documents throughout development (IND to NDA)

6. Regional Admin Information
From IND to NDA
NOT Part of the CTD
Regional Admin Information
Module 1
Module 2
Phase 1: Focus
on Safety
NDA: Complete
Details
Nonclinical Summary
Nonclinical Overview
The CTD
Clinical Summary
Clinical Overview
Quality Overall Summary
Module 4
Nonclinical Study Reports
Module 5
Clinical Study Reports
Module 3
Quality

7. Regional Admin Information
From IND to NDA
NOT Part of the CTD
Regional Admin Information
Module 1
Module 2
Introduce
Protocols and
Study Reports
at each phase
Nonclinical Summary
Nonclinical Overview
The CTD
Clinical Summary
Clinical Overview
Quality Overall Summary
Module 4
Nonclinical Study Reports
Module 5
Clinical Study Reports
Module 3
Quality

8. Building the NDA from Phase 1
Development Plan
Pre-IND
IND
NDA, DMF
Post-Approval

9. Marketing Goals: the NDA
Label Claims, Target Product Profile
Clinical Studies that support the label
Nonclinical Studies that support the clinical plan
CMC Data for the commercial product
Meet regulatory guidelines, standards, and agreements for approval
Set your strategy with CTD summaries (Module 2)

10. Why CTD content management?
Global harmonization of submission content (regional differences are handled in a modular fashion)
Standardization of submission format from clinical to marketing; from IND to NDA
Allows for preparation of submission-ready document templates
Facilitates life cycle management

11. Submission-Ready Documents
Build the marketing application from Ph 1 to NDA and post-marketing
The modular approach to writing submissions; capture regional differences
Each section/attachment is a technical report, or a section within the report
Meet eCTD granularity rules; eCTD-ready
More efficient use of resources, expedites submissions, less cost and stress to the organization

12. Levels of Submission-Ready Reports (Module 3)
Key results, conclusions
For QOS
Summary
Summary of methods
Module 3 data
Body of Report
Key Tables, Figures, Graphs
Discussion
Complete data
GMP Info
Appendices
May not be submitted, on file
Protocols

13. CTD/eCTD Templates
Define content and format for each section/report, granularity for eCTD
IND  NDA content for use throughout the development process; gap analysis
Address CTD, ICH, agency guidance
Address agency agreements
Customized for each product
May be expanded into model reports

14. Why CTD Document Management?
The world revolves around regulatory (!)
Product approval and regulatory compliance are highest priorities
Now there is global standardization; no excuse not to “file” according to the CTD
Shared databases enhance communication, transparency, efficiency, and co-operation
Quality Systems requirements (ICH Q10)

15. Shared Info and Databases
Example: Control of Drug Product:
3.2.P.5.1 Specifications
3.2.P.5.2 Analytical Procedures
3.2.P.5.3 Method Validation
3.2.P.5.4 Batch Analysis
3.2.P.5.5 Characterization
3.2.P.5.6 Justification of Specifications

16. CTD Mapping
Map source documents and related data to each section of the CTD
For example: 3.2.P.5.4 Batch Analysis:
Certificates of Analysis
Raw data: chromatograms, etc.
Statistical analyses
Trend analyses
Batches in each phase of development
Information on batches
Get management approval of the MAP

17. Description of Batches
Stability studies
Commer-cial
Clinical studies
Clinical
Intended Use
Process
Batch Size
Mfg Site
Mfg Date
Batch #

18. Key CTD Needs and Tools Succinct, Key Messages CTD Summaries
Build NDA from IND,
Content Management
CTD-Ready Docs
Ease of authoring
CTD Templates
Project Management
Information Management
CTD Mapping
CTD Doc Management
Workflow, Processes
CTD Team

19. The CTD Team Set submission strategy Define submission content
Author standardized documents
Make documents accessible
Work with the extended team:
Regional offices
Business partners
Contract manufacturers, other contractors

20. Submission-Ready Documents
CTD Workflow
CTD, eCTD
Workflow
Document Management
Submission-Ready Documents
Content Management

21. Start Early in Development
CTD Content Management:
Templates from IND to NDA
Submission-Ready documents
CTD Document Management
CTD Mapping
CTD Repository, filing strategies
Get Management Approval up front
Get CTD Team ready from the start
Put this in everyone’s Objectives

22. Conclusions
Merge document management and submission management to align marketing goals early in development
This promotes clear communication, transparency, and teamwork
Submission-ready documents written with CTD/eCTD templates from IND to NDA enhance efficiency
CTD document management facilitates traceability in quality systems

23. Contact Information
Michelle Herrera Foster, Ph.D.
CTD Quality Consulting
NOTE: Survey of CTD/eCTD needs and solutions for module 3 in progress.