ICH Quality Topics Update

1
ICH Quality Topics Update

• Moheb M. Nasr, Ph.D.
• Office of New Drug Quality Assessment (ONDQA),
  OPS, CDER
• Advisory Committee for Pharmaceutical Science
  (ACPS)
• October 5, 2006

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Presentation

• Topic Introduction Moheb Nasr, Ph.D., CDER,
  FDA
• Q8 Pharmaceutical Development John Berridge,
  Ph.D., Pfizer
• Q9 Quality Risk Management H. Gregg Claycamp,
  Ph.D., CVM, FDA
• Q10- Pharmaceutical Quality Systems Joseph
  Famulare, OC, CDER, FDA
• Q4B Regulatory Acceptance of Robert H. King,
  Sr., CDER, FDA
• Analytical Procedures and/or
• Acceptance Criteria
• Discussion and Recommendations

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ICH Quality Topics Update

• Background Information
• A new ICH Quality Vision
• Where are we today?
• Implementation of the New Vision
• Challenges FDA Perspective
• Future Activities
• Questions to the Advisory Committee

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ICH - Objectives

• The International Conference of Harmonisation of
  Technical Requirements for the Registration of
  Pharmaceuticals for Human Use (ICH) was
  established in 1990 as a joint regulatory/industry
  project to improve, through harmonisation, the
  efficiency of the process for developing and
  registering new medicinal products in Europe,
  Japan, and the United States, in order to make
  these products available to patients with a
  minimum of delay

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ICH Process

• Step 1 Consensus Building
• Steering Committee adopts concept paper
• Expert Working Group, rapporteured by an industry
  party, builds scientific consensus
• Step 2 Confirmation of Six-Party Consensus
• EWG submits consensus document
• Steering Committee signs off as Step-2 final
  document

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ICH Process (contd)

• Step 3 Regulatory Consultation and Discussion
• (a) Regulator publishes Step-2 document for
  regional consultation/comments
• EU Published as a draft CPMP guideline
• Japan Translated and issued by MHLW for internal
  and external consultation
• U.S. Published as FDA draft guidance in the
  Federal Register
• (b) Discussion of regional consultation comments
• Regulator consolidates regional comments
• EWG, rapporteured by a regulatory party from the
  same region as Step-1, discusses regional
  comments and builds consensus

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ICH Process (contd)

• Step 4 Adoption of an ICH Guideline
• EWG regulatory parties submit consensus document
• Steering Comm. regulatory parties sign off as
  Step-4 final document
• Step 5 Regulatory Implementation
• EU Published as CPMP guideline
• Japan Translated and issued as guideline by MHLW
• U.S. Published as FDA guidance in the Federal
  Register

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ICH Quality Topics (Prior to July 2003)
Q1 Stability Q2 Validation Analytical
Procedures Q3 Impurities Q4 Pharmacopeia Q5 Biotec
h Products Q6 Specifications Q7 GMP M4 Common
Technical Document
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ICH - A New Vision for Ensuring Product Quality
(Brussels, July 2003)

• A harmonized pharmaceutical quality system
  applicable across the life cycle of the product
  emphasizing an integrated approach to quality
  risk management and science
• New ICH guidelines
• Pharmaceutical Development (Q8), Quality Risk
  Management (Q9), and Pharmaceutical Quality
  Systems (Q10)
• High level guidelines, more visionary, less
  prescriptive, flexible regulatory approaches

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Accomplishments since July 2003

• ICH Q8
• ICH Q9
• ICH Q10 (In progress)
• ICH Q8 (R) (In progress)
• ICH Q4B (In progress, not part of the new
  ICH vision)

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Where are we today?

• Work in Progress
• Q8(R), Q10 and Q4B
• Implementation of the new vision by industry and
  regulators

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FDA - Implementation of the New Vision

• Intensive efforts in the US
• Across review and inspection programs
• Several public meetings, workshops and training
  programs
• Withdrawal of several FDA guidances
• Development of implementation guidances (in
  progress)
• Quality System, PAT, Comparability Protocol,
  Regulatory Agreement, ..
• Restructuring of ONDC
• CMC Pilot Program
• Pharmaceutical Inspectorate (PI)
• QbR Initiative
• CDER/ORA Site Selection process for GMP
  inspections.
• CVM pre-approval decision support system (PAIDSS)

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Challenges in Implementation - FDA Perspective

• Implementation Challenges
• Putting new concepts into practice (QbD, Design
  Space, Risk Assessment, etc.) not easy!!
• Diversity of products
• Different regulatory processes
• Expectations for a QbD - based submissions while
  addressing traditional requirements (dual
  processes)
• Integration of review and inspection
• Implementing while harmonizing
• Heavy workload and limited resources

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Future FDA Activities

• ICH Meeting in Chicago, October 21-26, 2006
• PDA/ISPE Workshop, Challenges of implementing ICH
  Q8 Q9, December 6 7, 2006 (Washington, D.C.)
  and February 2007 (Brussels)
• AAPS/ISPE/FDA Pharmaceutical Quality Initiatives
  Workshop, February 28, 2007

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Questions

• Do you agree with FDA implementation strategy of
  the new ICH quality vision?
• Should FDA implement additional QRM activities,
  given resource constraints?
• Should FDA continue to develop additional
  implementation guidances or rely only on ICH
  guidelines?
• Is it necessary to gain experience through
  implementation of the new concepts prior to
  development of additional guidelines?