1. Implementation of the E5 Guideline: Status and Next Steps

2. ICH and GCG International leadership role in scientific harmonization Requirements for drug development must have a scientific basis Value of harmonization of regulations – Brings innovative medicines to patients faster – Reduces delays in drug development – Minimizes duplication of clinical studies GCG: Outreach to non-ICH countries – ICH can add value in non-ICH countries – ICH is recognizing this value by expanding its activities

3. E5 Prospective harmonization to: – Reduce duplicative clinical testing – Minimize delays in drug development Aimed at facilitating registration of ‘legacy’ medicines in ICH regions Implementation is complex! Focus today must be relevance of E5 to public health and global drug development

4. E5 and Global Development Large, multi-center, multi-ethnic clinical development programs Inter- individual > inter-ethnic differences Data extrapolation often possible – Bridging studies conducted less frequently Harmonized E5 implementation is critical

5. E5 Principles 3 ethnic groups– Asian, Black, Caucasian – Country-specific studies are not scientifically justified Internationally accepted approach is critical – Scientific methodology – Regulatory process Bridging studies should only be conducted if scientifically necessary

6. E5 Criteria Steps in assessing the need for bridging 1.Can the existing data be extrapolated to the new population? 2.If not, are the differences that exist clinically relevant? 3.If they are, what study is required to allow the data to be extrapolated? This is the bridging study Steps 1 and 2 are ‘bridging justification’

7. E5 Implementation Must not cause disharmony among regulators Requires – Sound science-based assessment of Clinical Data Package and relevance to new region (‘bridging justification’) – Well-defined regulatory process Statistics has a role, but must consider – Statistical significance vs significance to patients and public policy – Questions that need to be answered before statistics are used Clinical relevance is key

8. Regulatory Environment Support innovation and public health Science based – internationally harmonized scientific standards Well-structured, consistent and transparent – E5 – early binding consultations – External advisory committee for appeals during approval process

9. Next Steps ICH is addressing implementation issues in a Q&A Continued dialogue between regulators and industry is critical – At all levels: company-national regulator; industry-national regulator; industry-regulator across countries Global drug development will eventually obviate the E5 guideline – We must continue to address E5 implementation – At the same time, we must start to address issues of global drug development We all have a public health responsibility to support harmonization