ICH Update: Developments and Future Directions

1
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

2
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

3
ICH Objectives

• Identification and elimination of the need to
  duplicate studies to meet different regulatory
  requirements
• More efficient use of resources in the RD
  process, as a consequence
• Quicker access for patients to safe and effective
  new medicines

4
Working Groups
SAFETY EFFICACY QUALITY
MULTIDISCIPLINARY
STEERING COMMITTEE Endorses topics, guidelines
and monitors progress
5
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)

6
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?

7
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

8
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

9
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
  (M4-CTD/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

10
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)

11
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

12
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 FDAs GMPs for the 21st Century
  initiative

13
New TopicsPromoting 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

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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

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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

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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

17
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

18
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

19
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

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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

21
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

22
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

23
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

24
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

25
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

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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

27
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

28
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)

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GCG Meeting 16 November 2004, Yokohama, Japan

• GCG Co-chairs
• Dr. Yves Juillet (European Industry)
• Mr. Mike Ward (Health Canada)

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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

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GCG Reflections 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

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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

33
Considerations (2)

• Managing expectations resources, realistic
  objectives
• GCG not a technical body
• Funding issues
• Stepwise approach build on successes

34
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.

35
Areas of work

• ICH technical guidelines
• Harmonization/regulation
• Training and capacity building

36
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

37
Regional Meetings Identified

• SADC January 05 implementation of ICH
  guidelines, including CTD
• ASEAN February 05 pharmacovigilance

38
Next Steps Regional Input

• 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

39
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