Transcript International Conference on Harmonization (ICH) and the

ICH Update: Developments and
Future Directions
IV Pan American Conference on Drug Regulatory
Harmonization
Boca Chica, Dominican Republic
2-4 March, 2005
Mike Ward
Health Canada
A Unique Approach

International Conference on Harmonisation
(ICH) was created in 1990
 Agreement between the EU, Japan and the
USA to harmonize different regional
requirements for registration of pharmaceutical
drug products
 Unique because joint effort by regulators and
associated pharmaceutical industry trade
associations
ICH Objectives

Identification and elimination of the need to duplicate
studies to meet different regulatory requirements
 More efficient use of resources in the R&D process,
as a consequence
 Quicker access for patients to safe and effective new
medicines
Working Groups
SAFETY
QUALITY
EFFICACY
MULTIDISCIPLINARY
STEERING COMMITTEE
Endorses topics, guidelines and monitors
progress
Retrospective
ICH – a ‘mature’ harmonization initiative
Over 50 technical guidelines, a dictionary of
medical terms, electronic standards and a common
format for drug registration
 Six ICH conferences to date, including ICH 6 in
Osaka, Japan, November 2003
 Witnessing increased interest in and use of ICH
guidelines globally
 Formation and evolution of Global Cooperation
Group (GCG)


Time to Reflect
Following over a decade of significant
achievements in the harmonization of
quality, safety and efficacy requirements for
the registration of new drugs in the three
ICH regions, is the work of ICH mostly
done? Will ICH become a maintenance-only
organization?
No, however…
Appropriate time to evaluate the future of ICH to
ensure:
– Proper balance between maintenance and new activities
– New topics are of high value and objectives are
achievable
– Most efficient use and management of resources
– Flexible enough to deal with evolving science and
technologies
– More transparent
ICH Output since 3rd Pan-Am
Conference, April 02 (1)
New products:

Five technical guidelines:
– 3 Quality: Stability (Q1E, Q1F), Biotech comparability (Q5E)
– 2 Efficacy: post-approval safety (E2D) and pharmacovigilance
planning (E2E)


Specifications established for electronic submissions:
eCTD
Four ‘Considerations’ documents: 3 on gene therapy, 1 on
gender and clinical trials
ICH Output since 3rd Pan-Am
Conference (2)

Responding to user needs and new data:
maintenance, improvement, clarification activities:
– Introduction of question and answers documents (M4CTD/eCTD, E5-ethnic factors, E2B(M)-transmission of safety
case reports)
– Revision of Quality guidelines on stability (Q1A) and
impurities (Q3B)
– Maintenance of limits for residual solvents (Q3C)
– New addendum to periodic safety update reports (E2C);
`granularity` annex to Common Technical Document
(CTD) guidance
ICH Output since 3rd Pan-Am
Conference (3)

MedDRA:
– Continual improvement: MedDRA version 8.0
scheduled for release March 2005
– Now available in 8 languages, including Spanish and
Portuguese
– New draft ‘Points to Consider’ documents on term
selection and data retrieval/presentation
– Release of first Standardized MedDRA Queries
(SMQs) – collaboration with Council for International
Organization of Medical Services (CIOMS)
ICH: Developments and Future
Directions
`Themes`:
– New topics: facilitating innovation
– New topics: promoting safety/public health
– Regulatory communication
– Maintenance/implementation
– Mechanics of ICH
– Transparency and communication
New Topics:
Facilitating Innovation

Examples:
– Q5E: comparability of biotech/biological products subject to
manufacturing changes
– Q8: pharmaceutical development
– Q9: risk management – application to quality requirements and
practices



Serve to facilitate innovation and improvement
More informed, risked-based approach to regulation
Consistent with FDA’s GMPs for the 21st Century initiative
New Topics:
Promoting Safety/Public Health

Examples:
– E2E: pharmacovigilance planning (completed)
– E14/S7B: QT prolongation (draft)

Topics identified by regulators
 Considered important in contributing to drug
safety and public health
 Potential new pharmacovigilance topics to be
considered by ICH following gap analysis of
current regional guidelines
New Topics: Other projects

Q4B: regulatory acceptance of (Japanese,
European and US) pharmacopeial
interchangeability
– Process established
– Piloting

S8: immunotoxicology
– Nonclinical test methods and decision tree for assessing
immunosuppression caused by non-biologic
pharmaceuticals
Regulatory Communication (1)

ICH has sought to enhance regulatory
communication through the development
of:
–
–
–
–
Standardized data elements, example: E2B
Controlled vocabularies, example: MedDRA
Common format for drug registration: CTD
Electronic specifications and standards for the
transmission of such information, example:
ESTRI and eCTD
Regulatory Communication (2)

Benefits:
– Speak same language: promotes
communication
– Quality, accuracy and consistency of
information
– Improve timeliness of communications
(electronic transmission)
– CTD/eCTD reduces delays and costs associated
with registration of drug applications
Regulatory Communication (3)

Status of CTD/eCTD implementation:
– As of July 2003 CTD mandatory in EU and
Japan, ‘highly recommended’ in US and
Canada
– Integration of CTD in existing regulatory
frameworks
– No significant difficulties encountered
– New era: eCTDs now being submitted in all
ICH regions
Regulatory Communication (4)

New: M5: Data elements and standards for
drug dictionaries:
– For use in describing medicinal products and
active ingredients
– Controlled vocabulary includes units, routes of
administration, pharmaceutical forms
– Electronic message specifications to be
developed
Maintenance/Implementation (1)

Critical aspects of the ICH harmonization process
considering need to ensure
– continued relevance and improvement of an ever-
growing number of guidelines
– consistent and intended use by regulators and industry

Tools/mechanisms:
– Qs and As, addenda, revisions, points to consider
– Change control and maintenance processes: eCTD,
E2B(M) and Q3C
– New: maintenance of ICH controlled terminology lists
Maintenance/Implementation (2)

Tools/mechanisms:
– MedDRA maintenance and support service organization
(MSSO)
– Creation of implementation working groups (e.g., for
CTD/eCTD, E2B(M)) and implementation tool (new)
– Implementation standing item on ICH Steering
Committee agenda
– General procedures and roles/responsibilities under
development
Mechanics of ICH



Given costs involved in harmonization activities, it is
important that effective structure and procedures are in
place to ensure maximum benefit is derived
Periodic reassessment of mandate, procedures within
context of ‘Future of ICH’
Most recent review in progress: June 03 – May 2005; focus
includes:
–
–
–
–
–
selection of new topics: business case now required
streamlining of procedures
clarifying roles and responsibilities
means of assessing implementation of guidelines
Transparency and communication
Transparency and
Communication

Reviewing current practices at regional and
ICH level
 Options to be considered to strengthen
transparency and communication
 GCG seen as increasingly important
mechanism for communication and
engagement with non-ICH regions and
parties
Global Cooperation Group
(GCG)
•
Established March 1999 as sub-committee of ICH
Steering Committee
• Formed to respond to this growing interest in ICH
guidelines
• Name reflective of desire to establish links with
non-ICH regions
• Membership :
– 6 ICH parties
– 2 Observers (WHO and Health Canada)
– ICH secretariat
Initial Mandate
•
•
Initial focus on information-sharing
Soon became clear that more active
engagement necessary to respond to
increasing interest in ICH and ICH
guidelines
Evolution In GCG Activities
and Thinking

Series of joint meetings with regional
representatives in preparation for ICH6
satellite session
 Parallel discussions within GCG on need to
be more relevant through establishing closer
ties with regional harmonisation initiatives
Osaka, Nov. 2003:
An Important Milestone
•
Endorsement by ICH SC of new Mandate
and Terms of Reference that call for
• the ongoing participation of regional
harmonization initiatives
• Greater transparency
Regional Harmonization
Initiatives

APEC
– Asia-Pacific Economic Cooperation

ASEAN
– Association of the Southeast Asian Nations

GCC
– Gulf Cooperation Council

PANDRH
– Pan American Network for Drug Regulatory Harmonization

SADC
– Southern African Development Community
PANDRH Representation

Initial selection during PANDRH Steering
Committee meeting in Madrid (February
2005):
– Dr. Carlos Chiale (ANMAT)
– Dr. Davi Rumel (ANVISA)

Review scheduled for next Steering
Committee meeting (March 2005)
GCG Meeting
16 November 2004,
Yokohama, Japan
GCG Co-chairs:
Dr. Yves Juillet (European Industry)
Mr. Mike Ward (Health Canada)
GCG Role and Procedures

Definition of GCG membership
– Maximum of 2 permanent representatives per
regional harmonization initiative
– Representatives should solicit/present views of
regional initiatives

Criteria for harmonization initiative to
participate in GCG
 GCG principles: openness and transparency
GCG Reflection’s Paper:
Mission, Activities and
Operations of GCG

Issue: While new terms of reference
provide authority, tools and rules (the
means), they do not define the mission of
the new GCG (the ends)
 Mission/vision necessary to guide and
validate future activities
Considerations (1)

Moving beyond bounds of ICH
 Serve as unique forum for harmonization
initiatives to discuss
– Best practices, lessons learned and innovative
approaches to harmonization and regulation
– ICH topics of interest
– Technical guidelines beyond scope of ICH
Considerations (2)

Managing expectations: resources, realistic
objectives
– GCG not a technical body
– Funding issues

Stepwise approach – build on successes
Draft Mission Statement
“To promote a mutual understanding of
regional initiatives in order to facilitate
harmonisation processes related to ICH
guidelines regionally and globally; and to
strengthen the capacity of drug regulatory
authorities and industry to implement
them.”
Areas of work

ICH technical guidelines
 Harmonization/regulation
 Training and capacity building
Identified Topics of Interest
•
•
•
•
CTD implementation and e-submission
GCP implementation
E5 implementation
Pharmacovigilance guidelines and MedDRA
implementation
Interest also expressed in:
- technical assistance expressed
- review process and data assessment
- joint GCP inspections
Regional Meetings Identified

SADC January 05: implementation of
ICH guidelines, including CTD
 ASEAN February 05: pharmacovigilance
Next Steps: Regional Input

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Comments on draft ICH guidelines (Q8, S8, then Q9)
Proposals for pharmacovigilance plenary session (May
05)
Identification and presentation of guideline
implementation and technical difficulties (formal
presentations at GCG Brussels meeting)
GCG teleconference organized for April 7, 2005
Next GCG meeting May 10, 2005 in Brussels
Summary

ICH continues to balance development of
important new topics with maintenance and
implementation activities
 New procedures and business case templates meant to improve efficiency and value of ICH
process
 Transparency, communication and engagement
through GCG seen as increasingly important