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

2. 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

3. 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

4. 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

5. 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

6. ICH Process (cont’d) 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U.S.: Published as FDA draft guidance in the Federal Register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

7. ICH Process (cont’d) 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

8. ICH Quality Topics (Prior to July 2003)
Q1 Stability
Q2 Validation: Analytical Procedures
Q3 Impurities
Q4 Pharmacopeia
Q5 Biotech Products
Q6 Specifications
Q7 GMP
M4 Common Technical Document

9. 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

10. 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)

11. Where are we today? Work in Progress
Q8(R), Q10 and Q4B
Implementation of the new vision by industry and regulators

12. 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)

13. 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

14. 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

15. 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?