Regulatory Perspectives and Clinical Trial Status in Korea

Transcription

1 Regulatory Perspectives and Clinical Trial Status in Korea In-Jin Jang, MD Seoul National University Hospital, Clinical Pharmacology and Clinical Trial Center

2 Outline Regulatory Perspectives History of regulatory changes and their outcomes GRP, IRB & accreditation of investigation sites Current issues Government initiatives for infrastructure building Clinical Trials in Seoul National University Hospital Seoul National University Hospital (SNUH) SNUH Clinical Trial Center (CTC)

3 Changes in Regulation related to Clinical Trials IND/NDA ; CT for foreign drug approval KGCP Enforced Rapid growth of Clinical trial infrastructure KFDA (with Toxicological Institute) ICH E5/E6 & Regulatory Reform IND/NDA rewrite - Bridging / MNCT New KGCP

4 Increased Number of Clinical Trials in Korea Separation of IND from NDA: Participation in international study enabled since December 2002

5 Clinical Trial Approval (CTA) Process KFDA Process Pre-IND Consultation Submission Review Approval Approval timeline : 30 days Effective Optional Consultation Fee : About US 4,000$ Protocol CMC Preclinical IB IRB Process ; Parallel review with KFDA process Contract With Hospital Submission Review Approval Protocol, ICF IB, CRF, CV

6 Reduced Time to CTA days 140 KFDA database year

7 Good Regulatory Practices of KFDA Amendment of Regulations Publication of Guidelines Good Review Practices Disclose Summary of Review Dialogues between customers and the KFDA Restructure KFDA to functional team for review quality and efficiency

8 Public Disclosure of Summary of Review To assure the transparency, fairness and balance, objectivity and consistency for reviewing process Summary of Review Product characteristics Related article of the regulation Reviewer s opinion List of submitted documents

9 Standardization and Harmonization of Institutional Review Boards Both public and private efforts Korean Association of IRBs (KAIRB); standardized SOP Education program for IRB reviewers and policy development grant from KFDA & MOHW SNUH IRB SOP, 1993 SNUH IRB SOP, 2005

10 Accreditation for Investigation Sites: a bottom line assurance for quality of clinical trial Class Phase I Phase II Phase III General Medicine Dental Medicine Total

11 National Technology Roadmap - Long-Range Strategic Planning STEPI/MOHW- MOST Clinical Trial Technology

12 Major Recommendation for Capacity Building 1. Developing Formal/Systematic Educational Programs Clinical Investigators, Clinical Pharmacologist, Clinical Trial Pharmacist, CRA, CRC, IRB members, Regulatory personnel etc. 2. Establishing Center of Excellence for Clinical Trials : National scale 3. Standardization of IRB Operation, and Quality Assurance/Accreditation mechanism 4. Good Regulatory & Review Practices: based on sound regulatory sciences 5. Improving Global Communications 6. Improving Public Awareness

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14 Education Program: from 2006 with governmental Support Clinical Investigators/Pharmacologist KSCPT, CTC/SNUH, Asan Medical Center IRB Member KAIRB, KSCPT Clinical Research Pharmacist/Nurse CTC/SNUH, KyungHee/Inje Univ(2004) Clinical Research Coordinator Samsung(2004) Data Management and Analyses CTC/SNUH Regulatory Reviewer - KFDA

15 Support for Clinical Trial Centers (MOHW) 4 million US dollar/5yrs from Government 4 million US dollar/5yars as matching investment from each Hospital plus α from industry and local government

16 Other Government Initiatives Presidential Committee on Healthcare Industry Innovation (); by presidential order (Aug ) Four areas of Planning Group on Healthcare Industry Innovation: Pharmaceutical industry, Medical device industry, Innovative healthcare cluster, & Healthcare R&D Operational from October 2005 to 2007 Pharmaceutical Industry Planning Group Functions Identify policy issues, research and evaluate plans for development of pharmaceutical industry Members: 15 One secretary general (member of the Presidential committee), government (4 directors of related bureaus of MOHW, MOST, MOCIE, & KFDA), industry (3), academia/healthcare (3), public research institutes (2), others (2) Major issues: pharmaceutical R&D, regulation, improvement of marketing and distribution system of pharmaceutical products and risk management

17 Seoul National University Hospital & Clinical Trial Center: 1 of 5 major investigation sites at university hospitals located in Seoul

18 Seoul National University Hospital: Statistics Main Hospital: Employees P/O Total Employees 3,655 Faculties 186 Clinical Faculties 105 Fellows 168 Interns & Residents 515 Administrative Staff 182 Nurses 1,157 Pharmacists 60 Medical Technologists 348 Classification Total Main Children s General Beds 1,627 1, Maternity Obstetric Bassinet Incubator Psychiatry Special Beds Hemodialysis I.C.U Recovery Emergency Affiliated Hospitals: SNUH Bundang Hospital; 1274 employees, 909 beds SNUH Healthcare System Gangnam Center

19 Number of Inpatients and Outpatients in SNUH Seoul National University Hospital: Ranked as the best hospital in Korea in the evaluation of all the clinical services by Korean government (Ministry of Health & Welfare) in New outpatients; 18.2% in main hospital 30.5% in Bundang hospital

20 Clinical research expertise & network of SNUH Oncology; developed the 1 st NME drug of Korea Endocrine; network of genetic research Stroke; PI of multicenter studies of PPI and others. Cardiovascular; hypertension, hyperlipidemia, etc. Andrology; PI of domestically developed PDE5 inhibitor (NDA submitted to KFDA) Dermatology; patch drug, cosmetics, etc. Stem cell research; Stem Cell Bank, Xenotransplantation research center Psychiatry; functional imaging Others; infection (largest AIDS patient pool in Korea), hematology, transplantation, allergy, pulmonology, epilepsy, depression, dialysis, hepatology (esp, hepatitis B & C), rheumatology, infertility, pain, medical devices Coordinating PI s in 3 multinational clinical trials; CV (1), oncology (2) studies in 2005 New complicated study protocols : Stem cell researches, Genomics, Gene banks, Embryo researches, Gene therapy

21 SNUH Clinical Trial Center: History June 15, 1996 May 15, 1998 Reshuffling of CTC organization / system Dec Government & Hospital grants to upgrade the facilities & personnel

22 Operation Facilities Research ward (3 rooms): 24 beds Outpatient clinics : 5 rooms Pharmacodynamic laboratories Neuropsychopharmacology (128 channel EEG, portable EEG) CV (QT, ABP, etc), dermatology, ophthalmology, etc. In house Pharmacy dept. Clinical laboratory & Serum bank - pharmacogenomic laboratory Analytical / Pharmacology lab.: LC MS/MS (3), HPLC (5), Drug screening, etc. Pharmacoepidemiology Division - DB & multicenter coordination

23 Data Management Data Management System Diagram (Audited by Lilly, Pfizer, GSK, Bayer) H/W and Networking & Backup ClinTrial 4 (Oracle based DB)

24 Clinical Trials in SNUH Number of trials Year Audit by Global Headquarter : Pfizer, Novartis, GSK, Lilly, Bayer, etc.

25 NME s approved in Korea by domestic Pharma. in collaboration with Sponsor Product Approval LG Lifescience SK Chemical Gemifloxacin (Quinolone) Sunpla (Platinum analog) / KFDA / US FDA / KFDA Choongwae Quinolone / KFDA Daewoong EGF / KFDA SK Chemical NSAID / KFDA Chongeundang Anticancer / KFDA

26 Centers of Korean Pharmacogenomic Research Network (KPGRN) Pharmacogenomics Research Center for DRUG METABOLISM Inje University Pharmacogenomics Research Center for Psychotropic Drugs Korea University 24 Univ. & Inst. Professors: 55 PhD researchers: 61 Researchers: 236 Headquarter at Seoul National University (CTC) PG Research Center for ADR /Common Technical Support Applying Pharmacogenomics to Clinical Trial : Bioethics & biosafety law (2005. Jan) storage & sending DNA samples became issue Phamacogenomic Research Center for DRUG TRANSPORTERS T M DN B D A r m I Yonsei University A r m I A T P T M DN B D AT Dr ug P AT P Phamacogenomic Research Center for Respiratory Drug

27 Functional Imaging (PET) in Phase I Trial of Antipsychotic Drug (YKP 1358, SK Corp.) for Later Phase Dose Assessment BP (Bmax/Kd) BP (Bmax/Kd) Before 2 hour 6 hour Before 2 hour 6 hour 0.5 Dopamine (D 2 ) receptor occupancy of a new antipsychotic drug using PET & [ 11 C]Raclopride

28 PK, PD & population typical profiles by NONMEM modeling ID: 11 ID: 12 ID: 13 ID: 21 ID: 22 ID: 23 ID: 24 ID: 31 ID: 32 ID: TIME TIME CE

29 Simulate D2 receptor occupancy at trough 350mg bid in 100 patients, 100 simulations distribution of 100 medians & percentiles Median P P P P90 At steady-state, 12 h post-dose 1. Occupancy median; 42 ~ 47.5% 2. Occupancy 10 percentile value; 32 ~ 37.5 % 3. Occupancy 90 percentile value; 52.3 ~ 58.4%

30 Goal of : a Center of BT/New Drug Development Industrialization Cluster in Korea Asian Trials & Global Trials A Clinical Research Centers C B D.. CRO CRO 1 CRO 2 3,.. Regional CTC A Regional CTC B Regional CTC E,.. Regional CTC D Regional CTC C BT/Clinical Trial Collaboration Center CTC Consortium Experts in each therapeutic area Decision Gate System Product development R&D Pharma. 1 (Domestic) R&D Pharma 2 (Domestic) R&D Pharma 3 (Domestic) Venture Venture Venture Company Company 1 Company 2 3 Multi-national Pharma. Multi-national Subsidiary 1 Pharma. Multi-national Subsidiary 2 Pharma. Subsidiary 3

31 Thank You!