1. Making Comments Count for High-Impact Regulations and Guidelines in the US Virginia (Ginny) Beakes-Read Executive Director, Global Regulatory Policy and Intelligence Eisai, Inc. Insert your logo in this area then delete this text box.

2. 46 th Annual Meeting Washington, DC - 2010 Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. (“DIA”), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. These PowerPoint slides are the intellectual property of the individual presenter and are protected under the copyright laws of the United States of America and other countries. Used by permission. All rights reserved. Drug Information Association, DIA and DIA logo are registered trademarks or trademarks of Drug Information Association Inc. All other trademarks are the property of their respective owners. 2

3. 46 th Annual Meeting Washington, DC - 2010 Commenting Process is Critical The Agency is seeking input –Much easier to influence FDA during an open comment period than trying to get FDA to initiate a new program or change a policy Well crafted and supported comments can effectively shape Agency thinking Regulatory documents and initiatives have a huge impact on industry and public health

4. 46 th Annual Meeting Washington, DC - 2010 Opportunities to Provide Comments Can comment directly to the Agency Can comment through a trade association, such as BIO, PhRMA, and AdvaMed –Pro: Trade Associations have collective, and therefore in ways a stronger voice –Con: May have to dilute message to get buy- in from other members Can comment both directly to FDA and through a trade association

5. 46 th Annual Meeting Washington, DC - 2010 US Regulatory Documents Regulations –Advanced Notice of Proposed Rulemaking, Proposed Rules, Final Rules Guidance Documents Concept Papers Federal Register Notices (may announce a program or other regulatory action)

6. 46 th Annual Meeting Washington, DC - 2010 Example of Comment to FR Notice FR Notice to withdraw CDER/CBER Intercenter Agreement of 1991 Agreement established which biologic products are regulated under the Federal Food Drug and Cosmetic Act and the Public Health Service Act Concern about effect on jurisdiction if ICA withdrawn –Would more biologics be regulated under the FDCA and therefore the 505(b)(2) pathway for Follow On Biologics could apply?

7. 46 th Annual Meeting Washington, DC - 2010 Commented on FR Notice Comment filed asserting that the ICA established principles that could not be modified without notice and comment Result: ICA was not withdrawn

8. 46 th Annual Meeting Washington, DC - 2010 Regulations Enacted to supplement/clarify laws, or to address a public health need (revision of Physician Labeling Regulation) Follow Notice and Comment Rulemaking –Agency issues proposed rule, solicits comments, has to address comments in final rule Once promulgated, regulations are binding on industry

9. 46 th Annual Meeting Washington, DC - 2010 Guidance Documents Follow Good Guidance Practices –21 CFR 10.115, 2000 –Level One and Level Two Guidances Published in Guidance Agenda Comprehensive List of Guidances Located in various FDA websites –CDER, and other Centers –Office of Commissioner for some cross-center guidances

10. 46 th Annual Meeting Washington, DC - 2010 CDER Guidance Website

11. 46 th Annual Meeting Washington, DC - 2010 Guidance Document Agenda

12. 46 th Annual Meeting Washington, DC - 2010 Level 1 Guidances Set forth initial interpretations of statutory or regulatory requirements Set forth changes in interpretation or policy that are of more than a minor nature Include complex scientific issues, or Cover highly controversial issues

13. 46 th Annual Meeting Washington, DC - 2010 Level 2 Guidances Set forth existing practices or minor changes in interpretation or policy Level 2 guidance documents include all guidance documents that are not classified as Level 1

14. 46 th Annual Meeting Washington, DC - 2010 Commenting – Level 1 Guidances Level One Guidances –Publish Draft Guidance Document –Comment period Comments are considered by FDA, but FDA does need to put responses in writing –Publish Final Guidance Document

15. 46 th Annual Meeting Washington, DC - 2010 Guidance Documents Not binding on industry –Recommendations, not requirements Guidances often used to add more detail to regulations –May be changed more easily than regulations Guidances also can be stand alone policy or scientific documents

16. 46 th Annual Meeting Washington, DC - 2010 Example of Commenting on FDA Guidance CDRH/OIVD/CBER – In Vitro Diagnostic Multivariate Index Assays CDRH issued Draft Guidance in September 2006, comments submitted, public hearing held, revised Draft issued in July 2007 –Trade Association comments vs. company comments No Final Guidance to date Genentech filed Citizen Petition addressing issue Still awaiting FDA action

17. 46 th Annual Meeting Washington, DC - 2010 Concept Papers Early step in developing a policy/program Generally have a conceptual framework, but need a greater understanding of issues Solicit feedback which can then be incorporated in a draft guidance document Increases likelihood that draft guidance more closely represents a viable approach

18. 46 th Annual Meeting Washington, DC - 2010 Core Elements of Action after Agency Publishes Document Appropriate stakeholders/experts in company review document Decide if issues are relevant to company If relevant, find right people to address Depending on complexity of issues, may need meetings to brainstorm and arrive at consolidated response Route response through internal review and approval process

19. 46 th Annual Meeting Washington, DC - 2010 Drafting Comments to Agency Documents or Initiatives Do: Use very clear language Provide thorough and persuasive rationale Make specific requests Don’t: Ask for clarification without giving a specific recommendation and justification Comment outside scope of document –If need to do so, explain what you are doing and why

20. 46 th Annual Meeting Washington, DC - 2010 Global Nature of Commenting ICH documents –Released by FDA, EMA, Japan May have slightly different timelines because of need to go through own Health Authority process –Decide whether to comment in all regions and be consistent with messaging Initiatives often ongoing by more than one Health Authority –Be aware of regional initiatives and speak with consistent voice if comment on more than one

21. 46 th Annual Meeting Washington, DC - 2010 Example of Comment on ICH Guidance – ICH S9 Nonclinical Evaluation of Oncology Products for advanced cancers Comments submitted on many specific scientific proposed requirements Justification given for comments and many comments accepted, sometimes using exact phrasing suggested Result is a more clear and precise ICH guidance

22. 46 th Annual Meeting Washington, DC - 2010 Electronic Filing of Comments

23. 46 th Annual Meeting Washington, DC - 2010 Rulemaking AND Guidances

24. 46 th Annual Meeting Washington, DC - 2010 FDA Federal Register Notices

25. 46 th Annual Meeting Washington, DC - 2010 FDA Docket Number

26. 46 th Annual Meeting Washington, DC - 2010 Search for Docket Number

27. 46 th Annual Meeting Washington, DC - 2010 Search Results

28. 46 th Annual Meeting Washington, DC - 2010 Guidance Document – 1 st Document

29. 46 th Annual Meeting Washington, DC - 2010 Comments or Questions? Thank you for your attention.