Regulatory Harmonisation
– Industry Perspective
Institute of Medicine
International Regulatory Harmonization Amid
Globalization of Biomedical Research & Medical
Product Development
Dr Peter Honig
VP Global Regulatory Affairs and Patient Safety
AstraZeneca L.P.
Why promote harmonisation?
Faster access
to medicines
Better use of
limited
resources
Sharing of
experience and
knowledge
Reduced
duplication
Fewer clinical
trials needed
2
Industry Strategic Priorities
• Increase Probability of Success (POS)
• Reduce Development Cycle Times
• Lower Development Costs
• Organic and inorganic growth in expanding economies.
All four may be facilitated by Global Development
Strategies and Regulatory Harmonization
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Industry Focus on Globalization
• Access
- Access to scientific talent
- Access to patients to facilitate clinical trial
accrual
- Access to lower cost suppliers and
operational support
- Access to markets
• Public
• Private
4
Changing Global landscape
Economic homunculus of the world in 2015
• Source : Worldmapper
• Note : Territory size shows the proportion of worldwide GDP measured in US$ equalised for purchasing power parity.
5
Globalization of Clinical Research
Density of Actively Recruiting Clinical Sites
(per million inhabitants)
Nature Rev Drug Dis (2008:7)
6
Global trends in Participation in Clinical Trials
Significant
Growth in
Asia and
other
Emerging
Economies
.
Nature Rev Drug Dis (2008:7)
7
Multi-regional Clinical Trials and
Regulatory Expectations
8
Different subset analyses are required by HAs
(assumes Phase III participation
China Ph III
data
China PK
study
Korea Ph III
data
ICH E5
Assessment
Asian data*
supportive
(Japan +
China +
Taiwan +
Korea)
ICH E5
Assessment
Asian data
(Japan +
China +
Taiwan +
Korea)
Own
domestic
Indian
patient data
or Mexican
patient data
or Vietnam
patient data
Science is not the only driver behind non-ICH clinical requirements
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Established harmonisation initiatives:
ICH
European
Union
• International Conference on Harmonisation
• Guidelines on Quality, Safety, Efficacy
• Common Technical Document
• European Medicines Agency, European Commission
and Heads of Medicines Agency
• Harmonised European regulated market
WHO
• Established medicinal, clinical and technical standards;
promotes regulatory capacity building training and work
sharing for Regulatory Authorities
PIC/S
• Pharmaceutical Inspection Convention and
Pharmaceutical Inspection Cooperation Scheme
• Inspection of manufacturing sites
FDA initiatives
• FDA/EMA QbD pilot
10
Regional Harmonisation Initiatives:
ICH - Global
Cooperation Group
(GCG)
• Regional Harmonisation Initiative representatives and
individual DRAs participate in ICH technical
discussions
Africa
• African Medicines Regulatory Harmonisation (AMRH)
• Funded by World Bank Trust Funds (BMG foundation)
Asia Pacific
• Asia Pacific Economic Cooperation (APEC) and Association of Southeast
Asian Nations (ASEAN)
• Asian Economic Community (AEC) - harmonization of technical standards
and regulatory requirements under the Pharmaceutical Product Working
Group (PPWG)
Latin America
Middle East
Honig/February 2013
• PAHO and the Pan American Network for Drug
Regulatory Harmonization (PANDRH)
• Gulf Central Committee for Drug registration
• League of Arab Nations
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Other initiatives:
WHO CPP
Scheme
• Globally accepted
• Avoids duplicated
reviews
Honig/February 2013
WHO PreQualification
Scheme
• Aids fast
registration of
essential
drugs
WHO
ICDRA
Conference
• Promotes
International
Harmonisation
Europe
• Clinical Trial
Regulation
• Harmonisation of
Clinical Trials in
Europe
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What challenges remain for existing initiatives?
Regulatory
Capability
Regional
Harmonisation
Initiatives
ICH
• Gap between emerging and developed
countries
• Need to focus on value added processes
• Initiatives based around existing
frameworks of regional economic
interests
• Inter-regional cooperation also required
• Focus on new chemical and biological
substances and dosage forms
• Harmonisation in life cycle management
also needed
13
What challenges remain for existing initiatives?
Clinical
Trials
Quality
Standards
GXP
Inspections
• Globalisation of CTs (larger population of
patients – faster recruitment)
• New regions, with local requirements
• Substandard products
• Expectations of regulators
• Capacity of regulators to conduct
assessments
• Duplicative re-inspection of sites preapproval (manufacturing, clinical trial sites)
• Recognition of other inspections and
certification
• FDA/EMA/TGA API inspection pilot
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Benefits of Harmonization are Clear
and Tangible
• Standardization of QSE requirements and format, content
of regulatory documentation.
• Reduction of cost and time for both regulators and industry.
• Improve the capacity of DRAs through more efficient and
collaborative use of resources.
• Bring new therapies of pre-specified QSE to patients faster
and at lower cost to all stakeholders
• Downward pressure on the price of QSE medicines by
enabling greater economies of scale and a leveled
regulatory playing field.
15
Reason for Optimism
• Progress in CTA requirements/timelines
• Investment in clinical trial and human protection
oversight infrastructures in non-ICH regions including
Asia
• Evolving understanding of impact (or lack thereof) of
ethnic and practice influences on acceptability of
foreign clinical trial data
• Recent movement on CPP requirements in non-ICH
regions (Singapore HSA, Taiwan)
• Growing acceptance of ICH guidelines and CTD
• APEC LSIF, AHC and Tripartite Initiative providing
regulatory science to inform policy and future practices
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Can we do even more?
Simultaneous
Global
Development
Data
Transparency
Supply Chain
Integrity
Adaptive trials
Training and
Capacity
Building
HTA &
Reimbursement
Decisions
Acceptability of
end points
Requirements
for companion
diagnostics
Pharmacoviilance
& Risk
Management
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Dank u
Danke
Grazie
Gracias
Obrigado
Merci
Tak
Спасибо
元気です ありがとう
謝謝
고맙습니다.
Ahsante Sana
• However you say it, it
means the same thing…..
world wide.
• Thank you!
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Back-up slides
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Examples of national requirements for Clinical sub-group analyses
and market specific documents
India
India Subgroup
Report
China
China CSR +
summary docs
South Korea
Bridging Position
Paper
Taiwan
Bridging Study
Checklist
Vietnam
Subgroup
report
Mexico
New Molecules Meeting
and Clinical Summary
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Examples of non-ICH clinical documentation
Country/Regional
Clinical Sub-group
Country/Regional Clinical Sub-group
requirements
analyses* required
analyses NOT required
China:
Mainland Chinese patients analysis including
‘China CSR’
China:
China PK study report
Mexico:
Mexican patient subgroup analysis for a New
Molecules Committee Meeting and Summary
China:
China Summary Documents & Clinical Study
Statistical Database
Vietnam:
Vietnamese patient analysis for the
‘Vietnamese CSR’
China:
China Special Review Process application
(if required)
Korea:
Korean patient analysis for the Bridging
Position Paper
Brazil:
Therapeutic Index
India:
Indian patient analysis for the Indian Summary
Association of South East Asian Nations:
ASEAN format CTD
Taiwan:
Asian** patient subgroup analysis for Bridging
Study “Checklist”
General:
International Clinical Document &
Summary of Medical Benefits
* Clinical Sub-group analyses = Country or region specific sub-analysis of key efficacy and safety endpoints including SAEs and
most common AEs
** Asian used to mean Japan + China + Korea + Taiwan
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