Regulatory Harmonization: Regulatory Harmonization: Regulator’s PerspectiveRegulator’s Perspective

Institute of MedicineFebruary 13, 2013

Douglas C. Throckmorton, MDDeputy Director

for Regulatory Programs, CDER, FDA

Values to Harmonization Improved use of resources

Animals Patients Time Cost

Improved information to patients and prescribers Improved timely access to effective therapies

2

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

“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

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

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: broad6

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

Partners in Regulatory Harmonization: Interlocking Areas of Need

10

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

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

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

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

Partners in Regulatory Harmonization:

What is the Role of the Regulator?

15

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

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

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

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

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

The art of progress is to preserve order amid change and to preserve change amid order

---Alfred North Whitehead