Regulatory Harmonization: Regulator’s Perspective

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

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

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

4. Regulatory Harmonization: FDA Focus • “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 4

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

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

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. 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. 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

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

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

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

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

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

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

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 ---Peter Barton Hutt: Five Moral Imperatives of Government Regulation, in The Hastings Center report, February 1980

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

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….

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