1. Regulatory Harmonization: Regulator’s Perspective Institute of Medicine February 13, 2013 Douglas C. Throckmorton, MD Deputy Director for Regulatory Programs, CDER, FDA

2. Values to Harmonization Improved use of resources Animals Patients Time Cost Improved information to patients and prescribers Improved timely access to effective therapies 2

3. Central Points Harmonization/convergence is occurring focused on a wide range of activities from policy-setting to technical standards Continued progress requires that we keep in mind the different goals, needs, and skills of partners Regulators, as one partner, have an essential role in fostering harmonization 3

4. 4 4 “Today we recognize that to successfully protect U.S. public health, we must think, act, and engage globally. Our interests must be broader than simply those within our own borders.” Margaret Hamburg, FDA Commissioner  International Offices  Strengthening Regulatory Capacity Building  Harmonizing Science-based Standards  Leveraging Knowledge and Resources  Risk-based Monitoring and Inspection  Advancing Regulatory Science Regulatory Harmonization: FDA Focus

5. Examples of Ongoing Harmonization International Conference on Harmonization (ICH) Voluntary Exploratory Data Submissions (VXDS) meeting PIC/S CDER Forum Asia-Pacific Economic Cooperation (APEC) Themes: different partners, different goals 5

6. International Conference on Harmonization (ICH) Two critical foci in international harmonization: Regulatory policy-making ICH E1: Clinical Exposure needs for safety evaluation of drugs intended for the long-term treatment of non-life- threatening conditions Technical standards development Overarching: ICH Q7A on GMPs for APIs Specific: ICH M4: Common Technical Document ICH Q4B Annex 13 on Bulk Density and Tapped Density of Powders General Chapter Harmonization gains: broad 6

7. 7 PIC/S  Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme  FDA newly admitted (one of ~40 regulatory agencies)  Part of the global product “safety net”  Harmonization gains:  Sharing GMP information from a worldwide set of GMP inspectorates  Using inspectional resources more effectively through the voluntary sharing of redacted GMP and AP inspection reports  Harmonization of inspectional standards

8. 8 Voluntary Exploratory Data Submissions (VXDS) meeting Developed to provide ‘safe-harbor’ for industry and regulators to discuss the application of new science (e.g., ‘omics, antisense technologies) to drug development No questions out of bounds 53 meetings to date, ~50% with both FDA and EMA Issues discussed are proposed by companies: Wyeth and biomarkers related to renal cell ca (mTOR) Lily and biomarkers related to cytochrome variants influencing anti-platelet drug activity Gains: increased FDA/EMA regulatory expertise in new sciences and harmonization in approaching new kinds of data --Goodsaid, F., et al, Voluntary exploratory data submissions to the US FDA and the EMA: experience and impact. Nature Reviews Drug Discovery 9: 435 (2010)

9. 9 CDER Forum for International Drug Authorities Forum by CDER staff, hosting international regulators interested in learning about FDA drug regulatory process 15 meetings since 2005 Over 550 participants have attended from over 65 countries Recent meeting focus on Good Clinical practices: Sponsor CRO selection Clinical monitor qualifications Preparing for and conducting monitoring visits Harmonization gains: capacity-building, colleageality

10. Partners in Regulatory Harmonization: Interlocking Areas of Need 10

11. Regulatory Harmonization: Interlocking Areas of Need Developed (regulatory) world needs: Regulatory harmonization to support efficient discovery, development and production Drives interest in: Focused efforts to harmonize in areas where development is critical Consistent guidance (for both regulatory policy and technical standards) Efficient transparent decision-making 11

12. Regulatory Harmonization: Interlocking Areas of Need Developing (regulatory) world needs (in addition): Regulatory models to support their own regulatory infrastructure/capabilities Full integration into global regulatory efforts Drives interest in: Technical support in building regulatory expertise Global engagement in standards-setting, global harmonization/convergence efforts 12

13. Regulatory Harmonization: Interlocking Areas of Need Governments, NGOs and patients worldwide need: Focus on public-health outcomes: Does harmonization contribute to improvement in human life? Need timely access to high quality medicines Supply chain disruption Counterfeiting Poor manufacturing 13

14. Regulatory Harmonization: Complex Set of Groups, Skills, and Roles Pharmaceutical Industry Regulators/ Regulations NGOs: Foundations, Institutes, Academics, Partnerships Each with unique skills, needs, goals, resources, roles… Challenges: prioritization and progress 14

15. Partners in Regulatory Harmonization: What is the Role of the Regulator? 15

16. Regulatory Harmonization: Roles of the Regulator Uniquely situated to contribute to harmonization efforts: Legal role in application of regulations Focus on public health mission Regulators in unique position to see needs across disease areas Regulators in unique position to respond to needs Regulators have identified obligation to support improved regulation, aided by harmonization/convergence 16

17. 5 “Moral Imperatives” of Government Regulation Protect the Public from Harm Preserve Maximum Individual Freedom of Choice Guarantee Meaningful Public Participation in the Decision-Making Process Promote Consistent and Dependable Rules that are Equally Applicable to Everyone Provide Prompt Decisions on All the Issues that Arise in a Regulatory Context 17 ---Peter Barton Hutt: Five Moral Imperatives of Government Regulation, in The Hastings Center report, February 1980

18. 18 Regulatory Harmonization: Role of the Regulator Provide clarity on the rules in operation and how they’ll be interpreted Guidances, Rules, Standards Ensure level playing field Process transparency, access, equity, timeliness ‘Consistent and dependable rules that are equally applicable to everyone’ Provide thoughtful and informed regulation that does not stifle innovation

19. Role of the Regulator: Supporting Continued Progress Invest in collaborative partnerships: interdependence is the reality Broaden the conversations beyond usual partners and topics for models and expertise Acknowledge differences exist (e.g., between regulators, regulations, needs, values) Build opportunities to harmonize existing knowledge, databases and standards Be prepared to question assumptions 19

20. Conclusions Benefits of harmonization are unequivocal and broadly acknowledged We are making progress on a broad range of regulatory harmonization activities Wide range of needs, groups and activities Regulators have a well-defined role to play: Recognition that we should actively look for ways to share, not the alternative…. 20

21. 21 The art of progress is to preserve order amid change and to preserve change amid order ---Alfred North Whitehead