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