IND Process and IND Process and Global ClinicalGlobal Clinical Trials in KoreaTrials in Korea

In-Sook Park, Ph.DDrug Evaluation Department

Korea Food and Drug Administration

ContentsContents

3

Attractiveness ofClinical Trials in Korea

4

1 Introduction of KFDA

Clinical Trials Activities 2

Challenges & Changes

Korea Food and Drug AdministrationCommission

er

Policy Manageme

nt and Public

Relations Headquart

ers

Food Headquart

ers

Central Pharmaceutical Affairs Council

6 Regional KFDA

National Institute of Toxicology

ResearchNutrition

and Functional

Food Headquarte

rs ▪ Pharmaceutical Safety

Policy Team▪ Pharmaceutical Control

Team▪ Narcotic Control Team

▪ Clinical Management Team

Quality Management Team▪ Herbal Medicines Control Team

▪ Biologics Safety Team▪ Biologics Control Team▪ Bacterial Vaccines Team▪ Viral Vaccines Team▪ Blood Products Team▪ Recombinant Products Team▪ Cell and Tissue Engineering Products Team Biological Diagnostic Product Team

Medical Devices

Headquarters

Herbal Medicines Evaluation Department

Drug EvaluationDepartment

Hazard Manageme

nt Departme

nt

Food EvaluationDepartme

nt

Medical Devices

Evaluation Department

PharmaceuticalsHeadquarters

Biologics Headquarters

Chemistry and Cardiovascualr Drug Team

▪ Antibiotic and Oncology Drug Team

▪ Gastrointestinal, Pulmonary and metabolic Drug Team

▪ Narcotic and Neuropharmacological Drug Division

▪ Quasi-Drug Team▪ Bioequivalence Team Pharmaceutical Equivalence Team

▪ Cosmetic Team

▪ Herbal Medicines Standardization Team

▪ Herbal Medicinal Products Team

▪ Herbal Medicine Evaluation Team 2007.1

0

4. Jan. 4, 2000(enforced Jan. 1, ‘01)

2. Oct. 1, 1995

1. Dec. 28, 1987 • Establishment of KGCP (recommendation)

• Requirement for compliance of KGCP

• KGCP Amendment for Harmonizing with ICH GCP- Harmonized with ICH guideline E6- Protect the rights and safety of subjects- Responsibility of investigator

3. Dec. 12, 1999(enforced .Jul. 1, ‘00)

• Adoption of the Bridging Concept - Harmonized to ICH guideline E5 - Diverse bridging strategies were required

Major Regulatory Changes

6. Dec. 3. 2002

• Introduction of IND System - Separation between developmental clinical stage and commercial product approval, such as IND and NDA - Participation in international study enabled

7. Jun. 30. 2006 • Organization of Clinical management Team

8. Jan. 4. 2007 • Introduction of Joint-IRB

Review Process in KFDA

Applicants

Civil Support Teamor KiFDA system

Phar. Safety Policy TeamClinical Management Team

Drug Evalu. Dep. CPAC

①Application

②Technical Documents CMC, Pharm/Tox and Clinical data

Administrative ②Documents Report ③

③

④Review Report

Advice

⑤Approve(Reject)

Approve(Reject) ⑥

Pharmaceutical Headquarters

Demand

All application documents could be submitted by KiFDA online system with electronical documents from Oct. 2nd, 2006

Kifda Online System

Kifda system is improving transparency and publicity Sponsor can online check the review status/progress Inform sponsor through Kifda system when reject

or more information is required Kifda system started on October 2, 2006 www.kifda.kfda.go.kr

42 31 28 27 38

9775

90110

134

1817

4661

95

108

147

5

0

50

100

150

200

250

300

`98 `99 `00 `01 `02 '03 '04 '05 '06 '07

Local Multinational

No.

of

Cli

nic

al T

rial

s

Year

• Adoption the bridging concept• Participation in multinational trial enabled

Implement ICH-GCP

Adopt IND concept (CSA < 2 months)

Government-designated regional clinical trial center

Change review process in KFDA/(DED)

Clinical Trials approved by Clinical Trials approved by KFDA KFDA

241% growth

Change in Proportion (1)

24

22

83

7

28

42

107

8

54

50

105

9

49

86

143

3

0

50

100

150

200

250

300

'04 '05 '06 '07

Phase 1 Phase 2 Phase 3 Phase 4

17

46

7

3

19

71

2

217

83

7

7

46

93

1

0

20

40

60

80

100

120

140

160

'04 '05 '06 '07

Phase 1 Phase 2 Phase 3 Phase 4

Multinational Trials

Change in Proportion (2)

Regulatory Hierarchy

GUIDELINEGUIDELINE

LAWLAW

ENFORCEMENTENFORCEMENT

• Pharmaceutical Affairs Law

• Enforcement regulation of Pharmaceutical Affairs Law

• Korea GCP Guideline• CTA Guideline• Guideline for Accredited Clinical Institutes

Regulations for Clinical Regulations for Clinical

TrialsTrials

Protocol approved by KFDA

Only at the accredited clinical sites

Qualified investigator

Protect the right and safety of subjects

Informed consent before enrollment of subjects

Investigational drugs

Essential Elements in Clinical Trials

defined in the Enforcement regulation of Pharmaceutical Affairs Law

Purpose

– To assure the quality of clinical study and institutes

What are essential to accredit?

– Appropriate facilities and equipments

– Pool of personnel to support the clinical study

– Activities of IRB

– Education program of GCP

– Structures and activities to manage the clinical study

How many sites ? 116 (Dec. 2007)

Accredited Clinical Accredited Clinical InstitutesInstitutes

Guidance of Accredited Clinical Institutes

CMC

Clinical

Phase IPhase IIPhase III

Bridging DMF CPP,etc

NonClinical

Pharmacology

ADMEToxicology

Dossier for NDA

defined in the Enforcement regulation of PAL

Protocol or

Protocol amendment

Safety and Efficacy Dossier

Preclinical, clinical experience

and investigator brochure defined in CTA guideline

In-house TS (testing

specification) dossier

Documents on

manufacture facilities

(for instance, GMP

Certificate)

Dossier for IND

Pre-INDConsultation Submission Review Approval

Submission Approval

ContractWith Hospital

• Protocol, ICF• IB, CRF, CV

Review

• Protocol• CMC• Preclinical• IB

KFDA Process

IRB Process ; Parallel review with KFDA process

• Optional Consultation

Approval timeline : 30 days

Clinical Trial Approval Process

Bridging Concept

Approval in Korea

New Product

Ethnic Factors (Ethnic difference)

◦ Intrinsic factor (genetic)

◦ Extrinsic factor (culture, environment)

Ethnic Sensitivity

Foreign clinical data

Bridging Data

“Bridging Data” = “Korean Data”

“Bridging Study” = “A trial conducted in Korean”

Evaluation

New Drug based on Bridging Strategy

Bridging data exemption 60%

Bridging study exemption

12%

Bridging study

28%

Exemption of Bridging study

Bridging study

Phase I Phase III

44%52%

Phase II4%

Phase I

92%

Phase II

Phase III

8%

• Based on the New chemical entity approved by KFDA from 2002 to Sep. 2007

Challenges for Challenges for implementationimplementation

• Qualification of Investigator

• Importance of IRB review

• Importance of SOP

• Need for Clinical Research Resources

• Need for Regulatory Service from Authorities

• Need for communication and harmonization with

Foreign Authorities

Strong Supporting Plan

Supported plan for Clinical Centers by MOHW• 9 Regional centers designated in 2004-2006• Support for Facilities, Operation systems, R&D etc. • $ 0.5 1 million/center/yr for 5 years∼

Ko-NECT (Korea National Enterprise of Clinical Trials)

• Clinical Hub of North-East Asia• Regional centers will be increased by 15 centers until 2010• Regional centers will be network• Training center and Development center to support clinical trials

MOHW : Ministry of Health and welfare

Prof. Byung-Hee Oh: Cardiology, SNUH Global PI of Aliskiren, Norvatis

Prof. Yoon-Ku Kang: Oncology, AMC Global PI of Xeloda Phase III study in GC, Roche

Prof. Young-Joo Bang: Oncology, SNUH Global PI of Sunitinib Phase II study in GC, Pfizer

Prof. Sun-Young Ra: Oncology, YUMC AP PI of Sunitinib Phase II study in RCC, Pfizer

Prof. Sun-Woo Kim: Endocrinology, SMC Global PI of Vildagliptin, Phase III study in T2DM, Norvatis

Dr. Jin Soo Lee: Oncology, NCC Global PI of ZD6474 Phase III study for LC, AZ

Prof. Joon Soo Kwon: Psychiatry, SNUH Global PI of 11286 Sertindole, Phase III study for schizophrenia, LundbeckMore than these…..

Korean Investigator’s Contribution to Global Trials

What’s attractiveness?

• Attractive Pharmaceutical Market10th largest in the world & 2nd largest in AP

(excluding Japan)Two digit growth every year: 16.8%, 2005Increasing healthcare expenditure

• Fastest aging country

• Life expectation: 75.1yr (M) vs. 80yr (F)

• Attractive Pharmaceutical Market10th largest in the world & 2nd largest in AP

(excluding Japan)Two digit growth every year: 16.8%, 2005Increasing healthcare expenditure

• Fastest aging country

• Life expectation: 75.1yr (M) vs. 80yr (F)

• Qualified Investigator and InstitutionGlobal PI in global trialsGood Clinical Trial Centers

• Experienced staff by training

• Facility: clinic, lab, pharmacy, archiving

• Efficient IRB process

• Qualified Investigator and InstitutionGlobal PI in global trialsGood Clinical Trial Centers

• Experienced staff by training

• Facility: clinic, lab, pharmacy, archiving

• Efficient IRB process

• Efficient Regulatory AgencyOpen communication with KFDA officerClear review timeline from 1 month up to

4.2 monthClear requirement for review & approval

• Efficient Regulatory AgencyOpen communication with KFDA officerClear review timeline from 1 month up to

4.2 monthClear requirement for review & approval

• Strong Support from Government60M USD government investment by 2010

for 15 regional CTCKorea National Enterprising of Clinical

Trial (KoNECT)MOU between KoNECT & J-CLIPNET

• Strong Support from Government60M USD government investment by 2010

for 15 regional CTCKorea National Enterprising of Clinical

Trial (KoNECT)MOU between KoNECT & J-CLIPNET

Thank You For Your AttentionThank You For Your Attention

Tel: 82-2-380-1703, Fax: 82-2-387-7857, Homepage: www.kfda.go.kr