A Case Study in the ValueA Case Study in the Value of Harmonisation of Harmonisation

Yoshikazu HAYASHIDeputy DirectorEvaluation and Licensing DivisionPharmaceutical & Food Safety BureauMinistry of Health, Labour and Welfare,

JAPAN

Philosophy/Purpose of Philosophy/Purpose of ICHICH

Eliminate Duplication in Tests to meet Different Regulatory Requirements

More Efficient Use of Resources Timely Access of Patients to

Safe and Effective “New Drugs”

Structure of ICHStructure of ICH ICH Participants Six Parties: EU, FDA, MHLW,

EFPIA, PhRMA, JPMA

+ Observers: WHO, EFTA, CanadaOrganization SC: Policy Issues EWG: Technical GLs Major Conferences: ICH 1 (’91) – ICH 5 (’00) ICH 6 (Osaka, Japan, Nov. 2003)

ICH GuidelinesICH Guidelines

ICH is neither a forum of global politics nor a trade negotiation,

but a scientific forumICH covers “new drugs”ICH guidelines provide “how to

collect data scientifically for marketing authorization”

ICH Process for Technical IssuesICH Process for Technical Issues

Step 1: Consensus Building/Drafting of GL

Step 2: SC Agrees to Releasing Draft GLStep 3: Regulatory Consultation/ Consolidation of CommentsStep 4: Adoption of GL by Regulators/ Publishing ICH GLStep 5: Regulatory Implementation

Mode of Mode of ImplementationImplementation

1. Formal Vehicles Amending Existing GLs Issuing New GLs Law Amendment2. Supplemental Vehicles Q&A, Compendium in MHLW Notif. Seminars, Publications by Private

Sectors (Japan Pharmacopoeia, etc.)

Harmonisation ProcessHarmonisation Process ((““Mickey Mouse” Mickey Mouse” Way of Progress!!)Way of Progress!!)

ICH

Japan

EU

ICH

USA

12 12 Year Achievements of Year Achievements of ICHICH

Understanding of InnovationCommon Regulatory Platform based on

ca. 50 GLs (Q, S, E) Improvement of Scientific GLsFacilitating Communication Among

Regulators & Between Regulators and Industries Toward the Common Goal

Effective Use of R&D Resources including Data Collected in Other Regions

Achievement in ICH Phase Achievement in ICH Phase II

(1990 – ICH4 in 1997)(1990 – ICH4 in 1997)

1. About 40 ICH GLs (Q, S, E) Substantially Completed2. Scientific Basis for Testing and Evaluation Harmonised3. Major Causes of Redundancy/ Duplication Eliminated

ICH Phase II Activity & FutureICH Phase II Activity & Future(ICH 4 (1997) - )(ICH 4 (1997) - )

1. Dealing More on Regulation Common Technical Document (CTD) ADR Report: MedDRA/Electronic Transfer2. New GLs on Emerging Issues3. Finalizing Uncompleted GLs/Maintaining

Existing GLs4. Globalization of ICH Activities (e.g. GCG)

MHLW’s implementation of MHLW’s implementation of ICH GLs ( ICH GLs ( ～～ July. 2003)July. 2003)

Quality: Q1~7 Stability, Impurities, Quality of Biotech.

Products, GMP for APIs, etc. Safety: S1~7 Carcinogenicity, PK, Reprotox, etc. Efficacy: E1~11 PSUR, Ethnic Factors, GCP, Pediatrics,

etc. Multidisciplinary: M1~4 MedDRA, CTD, eCTD, etc.

Impact of ICH; Regulator’s ViewImpact of ICH; Regulator’s View1. General Science-Based Discussion with Industry and Other DRA Facilitated2. Tests/Data for NDA Quality of Tests/Data Improved More Foreign Data Submitted3. NDA Review To Improve NDA Review Review Reform Collaboration among DRA

Implementation of New Implementation of New GCPGCP

1. Amended Regulations PAL (’96), GCP Ordinance (’97) Effective Step-by-Step, 100% in April ’98

2. “Hollowing Out” of Clinical Trials in Japan?

MHLW’s Role/Responsibility to Encourage CTs Ethically Wrong to Depend on CTs Abroad? Japan’s CTs Exposed to Global Competition

(Cost, Quality, etc.)

Acceptance ofAcceptance of Foreign Clinical Data Foreign Clinical Data

1. MHLW’s Past Policy Accept if GCP, Raw Data, Japan’s GL PK, Dose-Finding, Ph3 DB on Japanese

Population

2. New GL based on E5 & Expectation Scientific Bridging Study Consultation Encouraged on Completeness

Data-package for Bridging Data-package for Bridging StudyStudy

PK/PD study

Japanese data Foreign data

PK/PD study

Bridging study Study for bridging

Comparative study

Long term study

Study on patients

with risk

Comparative study

Long term study

Study on patients

with risk

Number of ConsultationNumber of Consultation

0

50

100

150

200

250

300

No. ofconsul

1997 1998 1999 2000 2001

No. ofconsultation(total)No. ofconsultation(bridging)

How CTD is implementedHow CTD is implementedby MHLWby MHLW

GAIYO of GAIYO of Q,S,EQ,S,E

NDA Application Form

Report QReport Q Report SReport S Report E

CTD ModulesCTD Modules

II

II AII A II BII B II CII C

IIIIII IVIV VV

DossierDossier

+ other region specific information

CTD will be facilitatingCTD will be facilitatingHarmonized Application Dossier

(Content and Format)Synchronized R&D StrategySynchronized NDA Submission to

EU, US and JapanNDA Review CooperationSynchronized Approval and

Marketing

Global Cooperation Global Cooperation GroupGroup （ （ GCG)GCG)

Created in 1999 to make information available on ICH activities and GLs

Some principles GCG Resource for information and data

reference GCG will not seek to impose its views GCG will provide information upon request

from non-ICH countries

Evolution of GCGEvolution of GCGInteraction with non-ICH Regional

Harmonisation Initiatives (APEC, ASEAN, PAHO/PANDRH, SADC)

The Challenges are: Varying Capacities Across A Region The Importance of Training Implementation of any ICH GLs in a

Stepwise Fashion Interest in Specific Topics (GMP for APIs,

GCP, Ethnic Factors, Stability)

ICH6 Program (Nov. 2003)ICH6 Program (Nov. 2003)Nov. 12 Nov. 13 Nov. 14 Nov. 15

Satellite ICH6 Main SessionPartnerships in Harmonisation (by ICH GCG)

MedDRA User’s Group

Gene Therapy

Welcoming RemarksNew Horizon for the Pharmaceutical Sector

CTD – Shared Perspectives on Implementation

CTD Breakout Sessions

Quality: Q1D, E, F, Q3A&B(R), Q3C(M), Q4/Q6A, Q5E, Quality System (GMP)

Pharmacovigilance and Regulatory Communication: E2C(A), E2D, E2E, E2B(M), MedDRA

Safety and Efficacy: S7B, E14 (QT), E5, Immunotoxicology

GlobalCooperation

Future Challenges

Close of Conference

Challenging Topics inChallenging Topics inICH6 ConferenceICH6 Conference

Shared Experience on the Implementation of CTD

New Pharmacovigilance Topics Quality Systems for the 21st Century (GMP) Comparability of Biotechnological/Biological

Products Safety Pharmacology and Clinical Evaluation of

QT/QTc Interval Prolongation Partnerships in Harmonisation Future Challenges facing ICH Gene Therapy

Do not miss the Do not miss the forthcoming ICH6!forthcoming ICH6!

Final Announcement

http://www.ich.org/ich6tris.html

Conference Registration and Hotel

Reservation are accessible

ICH in futureICH in futureTimely Access of Innovations for

Patients around the WorldChanging Environment – Regulations

and SciencesMaintenance and Implementation –

CTD and GLsPharmacovigilanceTransparency – Global Cooperation,

Large Conference

ICH WebsiteICH Website

Written Information Available on ICH Website:

www.ich.org

ご清聴ありがとうございました

Thank You