Transcript February 13 - Institute of Medicine

Regulatory Harmonization:
Regulator’s Perspective
Douglas C. Throckmorton, MD
Deputy Director
for Regulatory Programs,
CDER, FDA
Institute of Medicine
February 13, 2013
Values to Harmonization
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Improved use of resources
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Animals
Patients
Time
Cost
Improved information to patients and prescribers
Improved timely access to effective therapies
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Central Points
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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
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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
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International Offices
Strengthening Regulatory Capacity
Building
Harmonizing Science-based
Standards
Leveraging Knowledge and
Resources
Risk-based Monitoring and
Inspection
Advancing Regulatory Science
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Examples of Ongoing
Harmonization
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International Conference on Harmonization
(ICH)
Voluntary Exploratory Data Submissions
(VXDS) meeting
PIC/S
CDER Forum
Asia-Pacific Economic Cooperation (APEC)
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Themes: different partners, different goals
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International Conference on
Harmonization (ICH)
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Two critical foci in international harmonization:
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Regulatory policy-making
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ICH E1: Clinical Exposure needs for safety evaluation of
drugs intended for the long-term treatment of non-lifethreatening conditions
Technical standards development
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Overarching: ICH Q7A on GMPs for APIs
Specific:
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ICH M4: Common Technical Document
ICH Q4B Annex 13 on Bulk Density and Tapped Density of
Powders General Chapter
Harmonization gains: broad
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PIC/S
Pharmaceutical Inspection Convention and
Pharmaceutical Inspection Co-operation Scheme
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FDA newly admitted (one of ~40 regulatory agencies)
Part of the global product “safety net”
Harmonization gains:
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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
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Voluntary Exploratory Data
Submissions (VXDS) meeting
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Developed to provide ‘safe-harbor’ for industry and
regulators to discuss the application of new science
(e.g., ‘omics, antisense technologies) to drug
development
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Issues discussed are proposed by companies:
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No questions out of bounds
53 meetings to date, ~50% with both FDA and EMA
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)
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CDER Forum for International
Drug Authorities
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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:
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Sponsor CRO selection
Clinical monitor qualifications
Preparing for and conducting monitoring visits
Harmonization gains: capacity-building,
colleageality
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Partners in Regulatory
Harmonization: Interlocking
Areas of Need
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Regulatory Harmonization:
Interlocking Areas of Need
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Developed (regulatory) world needs:
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Regulatory harmonization to support efficient
discovery, development and production
Drives interest in:
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Focused efforts to harmonize in areas where
development is critical
Consistent guidance (for both regulatory policy and
technical standards)
Efficient transparent decision-making
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Regulatory Harmonization:
Interlocking Areas of Need
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Developing (regulatory) world needs (in
addition):
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Regulatory models to support their own regulatory
infrastructure/capabilities
Full integration into global regulatory efforts
Drives interest in:
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Technical support in building regulatory expertise
Global engagement in standards-setting, global
harmonization/convergence efforts
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Regulatory Harmonization:
Interlocking Areas of Need
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Governments, NGOs and patients
worldwide need:
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Focus on public-health outcomes:
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Does harmonization contribute to improvement in human
life?
Need timely access to high quality medicines
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Supply chain disruption
Counterfeiting
Poor manufacturing
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Regulatory Harmonization: Complex
Set of Groups, Skills, and Roles
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Pharmaceutical Industry
Regulators/ Regulations
NGOs: Foundations, Institutes,
Academics, Partnerships
Each with unique skills, needs, goals,
resources, roles…
Challenges: prioritization and progress
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Partners in Regulatory
Harmonization:
What is the Role of the
Regulator?
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Regulatory Harmonization: Roles
of the Regulator
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Uniquely situated to contribute to
harmonization efforts:
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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
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5 “Moral Imperatives” of
Government Regulation
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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
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Regulatory Harmonization: Role
of the Regulator
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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
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Role of the Regulator:
Supporting Continued Progress
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Invest in collaborative partnerships:
interdependence is the reality
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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
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Conclusions
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Benefits of harmonization are unequivocal
and broadly acknowledged
We are making progress on a broad range of
regulatory harmonization activities
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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….
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The art of progress is to preserve
order amid change and to preserve
change amid order
---Alfred North Whitehead
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