An Industry Perspective on ESubmissions to CDER

1
An Industry Perspective on E-Submissions to CDER

• John F. Wood, MBA, RAC
• Director, Regulatory Affairs
• Amylin Pharmaceuticals, Inc.
• San Diego, CA
• June 27, 2002

2
Overview

• Background
• Amylin Perspective
• San Diego Biotech Environment
• Amylin Pharm.
• Amylin NDA past experience
• Amylin Lessons Learned
• Amylin NDA/CTD Planning
• Future Initiatives at FDA re e-Subs

3
Background

• FDA cites e-subs offer improvements in
• Processing efficiency
• Submission quality
• Reviewer efficiency
• Review management
• Efforts to go electronic hampered by inconsistent
  submissions that are small in number (few
  reviewers have seen full e-sub)

4
Faster, More, Better!

• FDA is pressured for faster review times
• Regulatory Professional is often given less time
  to do more
• Technology makes things possible that were not
  before
• To add value, processes must be faster and
  maintain or surpass quality

5
New Drug Approval Time by Year
Median of Total Approval Times (in months)
6
San Diego Biotechnology

• 250 companies
• Most lt 500 Employees
• Average Market Cap is lt 1 Billion
• Small business fee waiver
• No waiver from GMP, GCP, or GLP or other
  Regulations

7
Amylin Pharmaceuticals, Inc.

• Founded, 1987
• Peak employment 300 people, 1998
• Layoffs in April 1998 and October 1998
• 39 employees January 1, 1999
• 150 employees December 2000
• 224 employees June 2002

8
SYMLIN NDA

• Large Complex Submission
• Planned initially as a paper submission
• Large majority of documents were scanned
• Limited integration among systems
• Publishing used to clean scanned documents
• Documents stored in Electronic Document
  Repository
• Final Submission was Fully Electronic assembled
  manually

9
CRF Scanning
Paper from CRO upon DB lock
QA
QA
QA
e-Rep
Bookmark
145,000 pages
Paper to Storage
1.4 million pages
10
Electronic Submission
Paper
E-files CSR CMC Preclin Sum
Convert Format
QA
QA
QA
e-Rep
e-Sub
QA
Paper files CSR CRF CMC Preclin
Scanning
QA
QA
11
SYMLIN NDA

• March 2000, first SYMLIN documents available for
  publishing/assembly
• December 7, 2000, submit eNDA for Symlin (600,000
  pages)
• January 2001, eNDA filed by FDA
• October 2002, approvable letter received
• Ongoing clinical trials to address issues

12
The Morning After

• The FDA doesnt read these things!
• They are so stupid to make us do this!
• I cant believe I submitted electronically!
• If I could just call them to make a few changes!
• Im so stupid
• Maybe it wasnt that bad, what would have been
  2000 volumes I put in a single tape!

13
Dealing with Catastrophic Change - 5 Stages

• Denial
• Anger
• Bargaining
• Depression
• Acceptance

14
Lesson Learned

• Leave terra firma behind
• Think electronically
• Act electronically
• From beginning to end

15
Acceptance

• Advantages
• Populate Submission Template on Rolling Basis
• Changes on the fly
• Global Submissions
• Limited Physical Size
• Environmental
• Ease of Review
• File Sharing Know thy NDA
• Future of Drug Development and Regulatory Affairs

16
Planning for the next one

• What we are doing differently
• Regulatory Active in Submission Planning
• Early commitment for an e-CTD
• Table of Contents of the Submission as PM tool
• Electronic Publishing Templates/Training
• EDMS
• Repository
• Workflow

17
Planning for the next one

• What we are also doing differently
• Granularity
• Metadata and Attributes
• Publishing Software Evaluations
• EDMS gt Publishing integration

18
Record Flow From Field to FDA
Administrative
FDA Elec. Doc. Control Room
CMC
EDMS
Publish
Preclinical
Clinical EDC Scanning Word process SAS Spreadsheet
Field
Sponsor
FDA
19
Savings

• Bookmarks and hyperlinks internal to original
  documents (Word and Framemaker)
• More links, less work
• Less last minute scramble
• Documents more useful for the writing process
• Ongoing Submission Assembly
• Full Text Searches
• Process efficiencies
• Less time to submit and less time to
  review/approve!

20
Costs

• Hardware
• Software
• Dedicated E-submission people
• Training

21
Future Trends in e-subs to CDER

• CTOC
• E-IND
• Data Standardization
• H7
• CDISC
• Review Tools
• Patient Profile Viewer

22
Electronic IND to CDER

• CDER does not yet accept e-INDs
• Efforts ongoing to incorporate XML technology
  into IND submissions
• XML specs for e-IND expected 2003
• Cumulative Table of Contents, prototype available
  demo

23
Links

• http//www.fda.gov/cder/regulatory/ersr/default.ht
  m
• Overview of guidances and copies of past
  presentations
• Look for updates from DIA 2002

24
The End.

• Questions?