1. 11 A New Paradigm for Medical Products Regulation in Taiwan Taiwan Food and Drug Administration 2010.09.10

2. 2 22 TFDA Organization Chart 2

3. 3 33 Pharmaceuticals Regulation in Taiwan 3 Post-Market Management Quality Drug Injury Relief Research & Discovery Preclinical Testing NDA/ PMA GLP ADR/AE ★ Reporting Insurance cGMP Market GPvP ADR/AE Reporting IRB/GCP IND/IDE Pre-Market Approval GTP ★ ADR/AE: adverse drug reaction/adverse event

4. 4 1980 1990 20002010 1982 GMP 1999 cGMP 2010 PIC/S GMP 1993 Local clinical trial 2000 Bridging Study Evaluation in accordance with ICH E5 2001 Pivotal trial/ early phase trial 1998 CDE 2001 TDRF 2010 TFDA Milestones on Drug Regulation

5. 5 Establishment of TFDA and Reform of Drug Review System  Enhancing quality, efficiency, and transparency in reviewing of pharmaceuticals and medical devices  Fostering the development of biopharmaceutical industry  Promoting international harmonization on drug regulation 5

6. 6 Transparency and Quality Assurance  Review quality assurance: QA/QC task force (2010.03)  On-line Roadmap : for tracking review progress for sponsor (2010.05)  Implementation of Good Review Practice (GRP) (2010.07)  Disclosure of assessment report for NCE (2010.08) 6

7. 7 77 NDA/PMA Review Process Sponsor Application Technical and administrative document, GMP/PMF TFDA Review Team (TFDA Staff+ CDE) Assessment report Consult with AC experts for special concern Advisory Committee Sponsor Decision 7 Global New, Botanical product, Biosimilar product, etc.

8. 8 8 Establishment of modern Clinical Trial Environment in Taiwan  Preclinical GLP inspection  Meet international standard  GCP inspection  Follow ICH –E6 GCP  Enhancement of the quality of IRB  international: SIDCER or FERCAP certified IRB  domestic : DOH audited 38 IRB  Training for clinical trial professional  Investigators, clinical research coordinators (CRC), clinical research associates (CRA), study nurses etc.  Improvement of clinical trial Infrastructure 8

9. 9 99 Improvement of Clinical Trial Infrastructure  Government funded Research Centers  Grant $22 million (NT) in 2010  General Clinical Research Center (GCRC): 11 sites  Center of Excellence: 5 sites  Center of Excellence for Cancer Research: 8 sites  Site Management Organization (SMO)  Qualified sites for IND/IDE: 128 teaching hospitals 9

10. 10 MOU ★ between Taiwan Center of Excellence and International Pharmaceutical Company MOU assigning dateTaiwan-international pharmaceutical company 2007-09-30National Taiwan University-GSK 2009-03-25National Taiwan University-Novartis 2009-07-16National Taiwan University-Boehringer Ingelheim 2009-11-30National Taiwan University-Pfizer 2010-05-13Taipei Veterans General Hospital-GSK 2010-08-31Chung Gung Medical Hospital-Novartis 2010-09-01China Medical University Hospital -Novartis 10 ★ MOU: Memorandum of Understanding

11. 11 Taiwan Global Trials Sponsored by International Companies source: 2007~2010 Q2, CDE database Ranking International CompanyCase number (phase I-III) 1A49 2B35 3C31 4D26 5E 6F21 7G 8H19 9I 10J17 11Roche 15 12L15 11

12. 12 Clinical trials conducted in Asia as of July 12, 2010 East AsiaSouth AsiaSoutheast Asia Taiwan1792India1331Singapore692 Japan1523Pakistan150Thailand717 Korea Republic of1907Bangladesh76Philippines393 China1664Nepal13Malaysia326 HongKong519Sri Lanka14Indonesia116 Korea, Democratic People’s Republic of 0Afghanistan7Cambodia15 Vietnam70 Myanmar4 Total7,405Total1,591Total2,333 Source: http://www.clinicaltrials.gov

13. 13 Clinical Trial Environment in Excellent Centers CountryTaiwanKoreaChina Population22.9 M48 M1300 M Cost  Approval of Protocol 1~1.5 Months 2~3 Months  8~12 Months Investigator (US trained)  Data Quality  Medical staff Patient retention  13 source: TrialTrove, May 2009

14. 14 International Cooperation  Memorandum of Understanding with Australia  EOLs ★ : GMP inspection & AE information sharing with USA, EU, and Switzerland  TCP ★ ISO 13485 audit report sharing with 12 EU Notified Bodies  Application of PIC/S membership  APEC (LSIF, ISTWG), ICH-GCG and etc.  Future works:  Promote collaboration with Japan, China and Korea, Singapore and Thailand  Participate WHO and related organization or meetings, such as ICDRAs ★ 14 ★ EOLs: exchange of letters ★ ICDRAs: International Conference of Drug Regulatory Authorities ★ TCP:Technical Cooperation Program

15. 15 Cross-Strait Cooperation in Clinical Trial  ECFA ★, Signed Between China and Taiwan (2010.06), opens a favorable cross-strait interaction mechanism and will improve the basis of promoting Taiwan’s cooperation with other countries  Cross-Strait cooperation on new drug research and clinical trial (in progress) ★ ECFA: Economic Cooperation Framework Agreement

16. 16 Non-CPP 1-CPP 2-CPP Major Breakthroughs (I) Relaxation of CPP 1. pivotal clinical trial in Taiwan 2. REMS/RMP if necessary 1. Early phase clinical trials in Taiwan 2. REMS/RMP 1. REMS/RMP if necessary Expected review time 720 days ( 2 years): 360days plus GXP inspection 360days Expected review time 300 days Expected review time 200 days ★ CPP: Certificate for Pharmaceutical Product from 10 advanced countries ★ REMS/RMP: Risk Evaluation and Mitigation Strategy/ Risk management plan ★ GXP: GCP,GLP,GMP

17. 17 Accelerated Review (For new agents with high industrial value) Abbreviated Review (FDA + EMA approved) Verification Review (Future with MOU) Priority Review (unmet medical needs) Priority review: Full documents Partial review, focused on bridging data, REMS, PSUR, etc. Verification based on reference agencies’ assessment reports Major Breakthroughs (II) New Review Tracks Accelerated Review: Full documents Expected review time ： 180 days Expected review time:150 days Expected review time ： 180 days

18. 18 Major Breakthroughs (III) CTN Scheme  Multi-national clinical trials approved by advanced country  One of Taiwan’s medical centers participated  Refer to Australian CTN scheme to accelerate the protocol review process  Implement since Aug 18, 2010 ★ CTN: Clinical Trial Notification

19. 19 Major Breakthroughs (IV) Biopark Cooperation  To plan the TFDA campus and establish the Biotech Industry Consultation and Education Resource Center in Nangang National Biotechnology Research Park

20. 20 Future Prospect 20  To create friendly regulatory environment  To promote excellent R&D infrastructure for innovative medical products QualityEfficiency International Harmonization Transparency

21. 21 Taiwan: Centrally Located in East Asia Tokyo 2’50 Seoul 2’20 Manila 2’00 Osaka 2’15 Sydney 8’50 Taiwan Beijing 3’00 Chongqing 3’00 Shanghai 1’20 Guangzhou 1’30 Hong Kong 1’40 Bangkok 3’45 Ho Chi Minh City 3’20 Kuala Lumpur 4’35 Singapore 4’20 Jakarta 5’00

22. 22 Thank You for Your Attention 22