A New Paradigm for Medical Products Regulation in Taiwan

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

2. TFDA Organization Chart 2 2 2

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

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

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

8. Establishment of modern Clinical Trial Environment in Taiwan Preclinical GLP inspection Meet international standard GCP inspection Follow ICH –E6GCP 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 8

9. 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 9 9

10. MOU ★ between Taiwan Center of Excellence and International Pharmaceutical Company ★MOU: Memorandum of Understanding 10

11. Taiwan Global Trials Sponsored by International Companies 11 source: 2007~2010 Q2, CDE database

12. Clinical trials conducted in Asia as of July 12, 2010 Source: http://www.clinicaltrials.gov 12

13. Clinical Trial Environment in Excellent Centers source: TrialTrove, May 2009 13

14. International Cooperation ★EOLs: exchange of letters ★ICDRAs: International Conference of Drug Regulatory Authorities ★TCP:Technical Cooperation Program • 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, Chinaand Korea, Singapore and Thailand • Participate WHO and related organization or meetings, such as ICDRAs ★ 14 14 14 14

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

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

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

21. Seoul 2’20 Tokyo 2’50 Osaka 2’15 Taiwan Manila 2’00 Sydney 8’50 Taiwan: Centrally Located in East Asia Beijing 3’00 Shanghai 1’20 Chongqing 3’00 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. Thank You for Your Attention 22 22