Recent Evolution of New Drug Review and Approval System in Korea September 28, 2000 Soo-Young Choi, Ph.D Korea Food & Drug Administration Seoul, Korea

New Drug Review and approval Process in Korea New Drug Regulations in Korea Korean Good Clinical Practice Future Perspectives

in New Drug Regulations Major Changes in New Drug Regulations Introduction of bridging concepts recommended in the ICH guideline Permission of multinational/multicenter clinical trials Implementation of science-based regulations Protection of rights, safety, and well-being of trial subjects Assurance of the quality of clinical trials

Central Pharmaceutical Toxicological Research KFDA Organization Chart Food Safety Bureau Pharmaceutical Safety Division Phrmaceutical Surveillance Narcotic Control Medical Divices Pharmacutical Safety Drug Evaluation Department Biologics Evaluation Department Natural Medicine Medical Device Office of Safety Evaluation Commissioner Deputy commissioner Central Pharmaceutical Affairs Council Planning& Mgmt 6 Regional KFDA National Institute of Toxicological Research

Safety & Efficacy Evaluation Central Pharmaceutical Step by Step Review and Approval Process Safety & Efficacy Evaluation Central Pharmaceutical Affairs Council Discovery Preclinical Development Phase II Clinical Trial Marketing Phase I Phase III Clinical Trial Approval Authorization Consultation

New Drug Review and approval Process in Korea New Drug Regulaion in Korea Korean Good Clinical Practice Future Perspectives

Major Points of Revision Introduction of a bridging concept Permission of multinational/ multicenter clinical trials Implementation of science-based regulations

Introduction of Bridging Concept Foreign clinical data can be accepted as full or partial support for approval Korean Phase III trial is not mandatory for approval New drugs can be approved in Korea with foreign clinical data and appropriate bridging data

Requirements for approval Category ~ 1999 2000 ~ Drugs under development Drugs with ＜3 years marketing experience or drugs marketed only in one country Drugs with ≥ 3 years marketing experience in ≥ 2 countries Phase I, II, III studies in Korea Phase III clinical study in Korea No clinical study Foreign data & bridging data Foreign data & bridging data from July, 2001 Post Marketing Surveillance (PMS) study is mandatory for new drugs.

Submission of Bridging Data For new drugs, * Appropriate bridging data should be submitted For the following drugs, however, the submission of bridging data is not mandatory for approval Orphan drugs or drugs used to be orphan drugs Drugs for AIDS or cancer treatment which pose threat to life because of no standard therapy or failure of a standard therapy, as recognized by the KFDA New drugs being developed in or outside Korea for which clinical trials in Korea are intended Diagnostics including radioactive drugs Topical drugs having no systemic effect Drugs proved to be of no ethnic differences in their safety and efficacy Any other cases KFDA approves

Permission of Multinational /Multicenter Clinical Trials Clinical study for drugs under development can be conducted in Korea at any stage of clinical development if safety of the drugs in human can be supported by foreign clinical data - not necessarily conduct a clinical study in Korea from Phase 1 Approval time of conducting a clinical study can be reduced from 115 days to 60 days by employing a simultaneous review system for clinical study protocol and application of importing or manufacturing investigational drugs Comparator drugs can be imported as investigational drugs by a third party

of science-based regulations Implementation of science-based regulations Abolished a minimum number of investigational sites and subjects required for each phase of a clinical trial (e.g., a minimum of 3 centers and 90 subjects for a Phase III trial) Abolished a minimum clinical response rate (e.g., 66.7%) required in the previous regulations Allowed submission of a minimum stability data to support stability of the drug during a clinical trial Activated sponsor/regulator meetings to discuss scientific issues occurred during the development phase

New Drug Review and approval Process in Korea New Drug Regulaion in Korea Korean Good Clinical Practice Future Perspectives

Historical Overview 1987 : Establishment of KGCP Guideline as a self-guideline 1990 : Accreditation of Clinical Trial Hospitals : 82 1992 : New Drug Committee in CPAC - Advisory Expert Review for Clinical Protocol/Reports 1993 : Governmental Initiatives for KGCP implementation - Written Informed Consent, Optional IRB Approval - Inspection(Audit) of Clinical Trial 1992-1994 : Revision of KGCP - enforcement, 1995. 10 2000 : Revision of KGCP - enforcement, 2001.1 - Almost identical to the ICH E6 Guideline

Revision of KGCP in Jan 2000 <Background> Harmonization of KGCP with ICH GCP to improve GCP standards <Major Points of Revision> Protection of rights, safety and well-being of trial subjects Assurance of the quality of clinical trials

Protection of rights, safety and well-being of trial subjects A procedure of obtaining informed consent has been described in detail Items regarding compensation to trial subjects has been provided It is required to include clergy or lawyer in the IRB Safety reporting procedure in accordance with the ICH guideline has been introduced

Assurance of the Quality of Clinical Trials Standard operating procedures (SOPs) to achieve uniformity of the performance of clinical trials are required It is required to implement and maintain quality assurance (QA) and quality control (QC) program for clinical studies The list of essential documents and their maintenance for the conduct of clinical trials has been specified

New Drug Review and approval Process in Korea New Drug Regulaion in Korea Korean Good Clinical Practice Future Perspectives

Future Perspective Our regulations will continuously be revised to facilitate domestic and global development of new drugs We try to minimize the number of bridging data or studies required for approval as our experience in evaluating bridging data and the scientific evidence accumulate It is recommended to obtain clinical data in Korean population during the development phase