Regulatory Harmonisation – Industry Perspective

Dr Peter HonigVP Global Regulatory Affairs and Patient SafetyAstraZeneca L.P.

Institute of MedicineInternational Regulatory Harmonization Amid Globalization of Biomedical Research & Medical Product Development

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Why promote harmonisation?

Faster access to medicines

Reduced duplication

Fewer clinical trials needed

Sharing of experience

and knowledge

Better use of limited

resources

3

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

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Changing Global landscapeEconomic 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.

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Globalization of Clinical ResearchDensity of Actively Recruiting Clinical Sites(per million inhabitants)

Nature Rev Drug Dis (2008:7)

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Global trends in Participation in Clinical Trials

Nature Rev Drug Dis (2008:7)

Significant Growth in Asia and other Emerging Economies

.

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Multi-regional Clinical Trials and Regulatory Expectations

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Different subset analyses are required by HAs(assumes Phase III participation

China

China Ph III data

China PK study

Korea

Korea Ph III data

ICH E5 Assessment

Asian data* supportive (Japan + China + Taiwan + Korea)

Taiwan

ICH E5 Assessmen

t

Asian data (Japan + China + Taiwan + Korea)

India, Mexico, Vietnam

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:• International Conference on Harmonisation• Guidelines on Quality, Safety, Efficacy• Common Technical Document

ICH

• European Medicines Agency, European Commission and Heads of Medicines Agency

• Harmonised European regulated market

European Union

• Established medicinal, clinical and technical standards; promotes regulatory capacity building training and work sharing for Regulatory Authorities

WHO

• Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme

• Inspection of manufacturing sitesPIC/S

• FDA/EMA QbD pilotFDA

initiatives

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Regional Harmonisation Initiatives:

Honig/February 2013

• Regional Harmonisation Initiative representatives and individual DRAs participate in ICH technical discussions

ICH - Global Cooperation Group

(GCG)

• African Medicines Regulatory Harmonisation (AMRH)• Funded by World Bank Trust Funds (BMG

foundation)Africa

• 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)

Asia Pacific

• PAHO and the Pan American Network for Drug Regulatory Harmonization (PANDRH) Latin America

• Gulf Central Committee for Drug registration• League of Arab NationsMiddle East

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Other initiatives:

Honig/February 2013

WHO CPP Scheme• Globally accepted• Avoids duplicated

reviews

WHO Pre-Qualification 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?• Gap between emerging and developed

countries• Need to focus on value added

processes

Regulatory Capability

• Initiatives based around existing frameworks of regional economic interests

• Inter-regional cooperation also required

Regional Harmonisation Initiatives

• Focus on new chemical and biological substances and dosage forms

• Harmonisation in life cycle management also needed

ICH

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What challenges remain for existing initiatives?• Globalisation of CTs (larger population

of patients – faster recruitment)• New regions, with local requirements

Clinical Trials

• Substandard products• Expectations of regulators• Capacity of regulators to conduct

assessments

Quality Standards

• Duplicative re-inspection of sites pre-approval (manufacturing, clinical trial sites)

• Recognition of other inspections and certification

• FDA/EMA/TGA API inspection pilot

GXPInspection

s

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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.

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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

Adaptive trials

Acceptability of end points

Requirements for companion

diagnostics

Pharmacoviilance & Risk

Management

HTA & Reimbursement Decisions

Supply Chain Integrity

Data Transparency

Training and Capacity Building

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• However you say it, it means the same thing….. world wide.

• Thank you!

• Dank u• Danke• Grazie• Gracias• Obrigado• Merci• Tak• Спасибо• 元気です ありがとう• 謝 謝• 고맙습니다 .• Ahsante Sana

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Back-up slides

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ChinaChina CSR +

summary docs

MexicoNew Molecules Meetingand Clinical Summary

South KoreaBridging Position

Paper

TaiwanBridging Study

Checklist

IndiaIndia Subgroup

Report

VietnamSubgroup

report

Examples of national requirements for Clinical sub-group analyses and market specific documents

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Examples of non-ICH clinical documentation requirementsCountry/Regional Clinical Sub-group

analyses* requiredCountry/Regional Clinical Sub-group 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