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

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

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

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

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

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draft CPMP guideline Japan: Translated and issued by MHLW for internal and external consultation U.S.: Published as FDA draft guidance in the Federal Register (b) Discussion of regional consultation comments Regulator consolidates regional comments EWG, rapporteured by a regulatory party from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

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

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

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

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)

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

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)

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

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

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?