Managing the Drug Development Process with eCTD Tools: Advantages of Preparing Submissions Electronically

1. Managing the Drug DevelopmentProcess with eCTD Tools:Advantages of Preparing Submissions Electronically Michelle Herrera Foster, Ph.D. June 9, 2005 RAPS Boston Seminar CTD Quality Consulting www.CTDQuality.com

2. Module 2 NonclinicalOverview ClinicalOverview NonclinicalSummary ClinicalSummary NonclinicalStudy Reports ClinicalStudy Reports Quality Module 3 Module 4 Module 5 ICH M4 NOT Part of the CTD RegionalAdminInformation Module 1 The CTD QualityOverallSummary CTD Quality Consulting www.CTDQuality.com

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

4. What are the advantages of the CTD? • Global harmonization of applications • Provides standards to prepare submission-ready documents in the IND phases • Standardization assists project management and information management • Facilitates life cycle management • Facilitates drug development planning CTD Quality Consulting www.CTDQuality.com

5. Presentation Topics • Regulatory Challenges and Transitions • Taking Advantage of New Standards • Content Management in Drug Development • Document Management per the CTD • Building the NDA from Phase 1 • Mapping and Gap Analysis • Electronic Tools and their Benefits CTD Quality Consulting www.CTDQuality.com

6. Regulatory Challenges and Transitions in Drug Development • Transitioning to the CTD • Requirement for electronic labeling (SPL) • Preparing for the eCTD • Life Cycle Management • Quality Systems CTD Quality Consulting www.CTDQuality.com

7. Electronic Labeling (SPL) • Structured Product Labeling (XML-based) • Supports electronic distribution/update over the life cycle of the drug • Electronic labeling to be required by FDA 10/05 CTD Quality Consulting www.CTDQuality.com

8. Taking Advantage of New Standards How to cope with evolving regulatory standards and get them to work in your favor And work more Efficiently CTD Quality Consulting www.CTDQuality.com

9. The Benefits of New Standards CTD Global harmonization, submission-ready structure eCTD, SPL XML technology, content management Life Cycle Management Change control, regional differences Quality Standards Quality and Regulatory planning hand-in-hand CTD Quality Consulting www.CTDQuality.com

10. Quality Systems ApproachFDA draft guidance 9/04 • Monitoring of Trends • Risk Assessment • Corrective Action • Preventive Action • Process Analytical Technologies Guidance Increased government-mandated structure can be used for better control of the process CTD Quality Consulting www.CTDQuality.com

11. Preclin – Ph 1 – Ph 2 – Ph 3 – NDAInformation Management Doc Management Functional Area CMC Development Docs GLP Docs Nonclinical GCP Docs GMP Docs Clinical Submission Docs CTD Quality Consulting www.CTDQuality.com

12. Information Management in Drug Development Why not manage your documents to meet every product development need, organized by regulatory approval categories? CTD Quality Consulting www.CTDQuality.com

13. Document Management per the CTD, in DP Manufacture CTD Quality Consulting www.CTDQuality.com

14. Building the NDA from Phase 1 P.1 P.2 P.3 P.4 P.5 P.6 P.7 P.8 S.1 S.2 S.3 S.4 S.5 S.6 S.7 Development Plan Pre-IND IND NDA, DMF Post-Approval CTD Quality Consulting www.CTDQuality.com

15. Submission-Ready Documents • Summary  Module 2 • Body of report  Module 3, 4, or 5 • Appendices  For the file Build the NDA from Phase 1 CTD Quality Consulting www.CTDQuality.com

16. Mapping and Gap Analysis • Map documents to the CTD • Perform a gap analysis for each stage of drug development • Define action items • Assign tech leads • Track progress CTD Quality Consulting www.CTDQuality.com

17. CTD Quality MAPExample CTD Quality Consulting www.CTDQuality.com

18. “Action Items” • Submission Requirements • Risk Reduction • Quality Systems • Pre-Approval Inspection CTD Quality Consulting www.CTDQuality.com

19. The Overlap of Regulatory and Quality Systems S.2, P.3 Mod 1 P.3 A.1 S.2.3, P.4, S.6, P.7 S.4, P.4, P.5 CTD Quality Consulting www.CTDQuality.com

20. Submission-Ready docs, Gap Analysis  Build the NDA from the IND  Filing/Version Control  Project Management  SPL requirement  eCTD submission  CTD Templates eCTD structure Document Management Link documents to project management software XML editor and template Reviewer Tools Life Cycle Management Benefits of Electronic Tools CTD Quality Consulting www.CTDQuality.com

21. CTD Templates • Structure guide (DTD) • Format/style guide • Detailed Content: • Regulatory guidelines: ICH, regional • Table shells • Instructions to authors • Granularity: Sub-headings • XML Features: • Tagging, linking • eCTD Compatible CTD Quality Consulting www.CTDQuality.com

22. “Bottom-Up” Drug Product Development CTD, eCTD Workflow Process Management Submission-Ready Documents Content Management CTD Quality Consulting www.CTDQuality.com

23. Conclusions • Electronic tools provide many benefits in planning and preparing regulatory submissions, and managing complex content • Drug development planning benefits from application of e-document tools, from the IND to the NDA • XML standardization helps you control your drug development process • XML tools can be phased in CTD Quality Consulting www.CTDQuality.com

24. References ICH: International Conference on Harmonization www.ich.org FDA: Food and Drug Administration (U.S.) www.fda.gov EMEA: European Medicinal Evaluation Agency (EU, Europe), www.emea.eu.int Michelle@ctdquality.com 978-922-6017 www.ctdquality.com CTD Quality Consulting www.CTDQuality.com