1. Regulatory Harmonisation – Industry Perspective Dr Peter Honig VP Global Regulatory Affairs and Patient Safety AstraZeneca L.P. Institute of Medicine International Regulatory Harmonization Amid Globalization of Biomedical Research & Medical Product Development

2. 2 Why promote harmonisation? Faster access to medicines Reduced duplication Fewer clinical trials needed Sharing of experience and knowledge Better use of limited resources

3. 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

4. 4 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

5. 5 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.

6. 6 Globalization of Clinical Research Density of Actively Recruiting Clinical Sites (per million inhabitants) Nature Rev Drug Dis (2008:7 )

7. 7 Global trends in Participation in Clinical Trials Nature Rev Drug Dis (2008:7) Significant Growth in Asia and other Emerging Economies.

8. 8 Multi-regional Clinical Trials and Regulatory Expectations

9. 9 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.

10. 10 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 sites PIC/S FDA/EMA QbD pilot FDA initiatives

11. 11 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 Nations Middle East

12. 12 Other initiatives: Honig/February 2013 WHO CPP Scheme Globally accepted Avoids duplicated reviews WHO Pre- Qualificat ion Scheme Aids fast registration of essential drugs WHO ICDRA Conference Promotes International Harmonisatio n Europe Clinical Trial Regulation Harmonisation of Clinical Trials in Europe

13. 13 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

14. 14 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 GXP Inspections

15. 15 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.

16. 16 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

17. 17 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

18. 18 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 고맙습니다. Ahsante Sana

19. 19 Back-up slides

20. 20 China China CSR + summary docs Mexico New Molecules Meeting and Clinical Summary South Korea Bridging Position Paper Taiwan Bridging Study Checklist India India Subgroup Report Vietnam Subgroup report Examples of national requirements for Clinical sub-group analyses and market specific documents

21. 21 Examples of non-ICH clinical documentation requirements