Introductions and Perspectives on International Harmonization

Transcription

1 Introductions and Perspectives on International Harmonization FDA/PQRI Conference on Evolving Product Quality September 17 th 2014 Mark Rosolowsky, PhD Vice President Global Regulatory Sciences CMC Bristol-Myers Squibb

2 Disclaimer The contents of this presentation are my own, and do not necessarily reflect the views and/or policies of Bristol-Myers Squibb or any other group with which I am affiliated.

3 International Harmonization Why harmonization: The ideal and current state Signs of convergence and divergence Agenda and Introduction of speakers

4 Ideal State One global set of CMC requirements One risk-based review of application for an efficient global approval One site inspection (or an inspection waiver based on historical GMP metrics) A regulatory process that enables sponsors to quickly implement continuous manufacturing and testing improvements which would facilitate patient access to medicines and avoid drug shortages

5 Current State Numerous CMC-requirements (many of which are not science or risk-based) Staggered Health Authority review and approval times resulting in inventory fragmentation and drug shortage risks Numerous, redundant Health Authority inspections

6 Health Authority Approval Times for a Single Manufacturing Change Adapted from: IFPMA draft paper on Global Supply Chain of Medicines for Human Health- Current Challenges and Future Imperatives (unpublished)

7 Complexities in Drug Product Inventory Example of how overlapping change approvals complicate drug product inventory Adapted from: IFPMA draft paper on Global Supply Chain of Medicines for Human Health-Current Challenges and Future Imperatives (unpublished)

8 Current Situation Adapted from: Appropriate Control Strategies Eliminate the Need for Redundant Testing of Pharmaceutical Products; T. Schreitmueller on behalf of IFPMA; WCBP January

9 International Harmonization: Some Signs of Divergence Brazil: BR-RDC 58/2013 Degradants in DP China: Two-step procedure has been reinforced for pre-cpp development pathway for Import Drug Registration US: Commercial site stability for new NDAs

10 International Harmonization: Some Signs of Convergence ASEAN Adopting QbD Approach to Process Validation Under Singapore Leadership APEC Biotherapeutic Products Roadmap to reach a high level of regulatory convergence by 2020 EU- US TTIP: EFPIA Contribution to Items for Regulatory Convergence EMA-FDA Pilot on QbD Applications International Symposium on Continuous Manufacturing PhRMA white paper on Regulatory Commitments and Post- Approval Change Management (in progress) Draft ICH Concept Paper (Q 12) on Lifecycle Management

11 Global Convergence of Post-Approval Change Regulations Offers a «Win-Win» Outcome for Regulators, Industry & Patients Harmonized post-approval regulations Change classification, procedures, dossier requirements Regulators Industry Patients IDEAL Allow better planning and execution of changes No additional country-specific High quality standard data to be created maintained globally Reduce complexity in supply STATE chain Reliable supply of high quality drugs to all patients GLOBALLY Prioritize based on criticality of change Facilitate assessment of changes Enhance collaboration/ knowledge sharing with other agencies Mutual recognition of regulatory decisions Transparency Slide adapted from IFPMA Global Regulatory Convergence - The Need and Opportunity for Global Post- Approval Variation Requirements of Biotherapeutics; 2014 APEC Meeting, Seoul, South Korea; by T. Schreitmueller Improved drug quality rapidly accessible to the market

12 Session Agenda Update on ICH Hot Topics: ICH Q3D and ICH M7: Assessment and Control of Mutagenic Impurities Mark G Schweitzer, Ph.D., Novartis Pharmaceutical Corporation Stephen P. Miller, Ph.D., FDA EMA-FDA Pilot on QbD Applications: FDA Perspective: Sharmista Chatterjee, Ph.D. FDA Industry Perspective: Ambarish Singh, Ph.D., Bristol-Myers Squibb Break 10:00-10:15 Opportunities for International Collaborations in Inspections Peter Kitz, Bristol-Myers Squibb Challenges in Getting Global Approvals for Post-approval Changes Andrew Chang, Ph.D., Novo Nordisk Panel Discussion 11:15-12:00

13 Backup

14 Questions for Panel and Audience What are most important challenges you face in International Harmonization (IH)? What harmonization successes can you share? What other examples of regulatory convergence do you know of? What can industry do to promote IH? What can FDA and other regulators do? What can ICH do? More guidances Fewer guidances What are primary concerns about submission of post-approval changes? Long review times License application integrity Inability to answer questions from HAs in timely manner Questions become non-value added after 1-2 HAs approve

15 Questions (continued) What are primary concerns about international inspections? Resource drain on organization to host Interruption of manufacturing operations Remediation effort (resources) to address observations Non-value added after 1-2 HAs visit Comments on PhRMA white papers to harmonize review/post-approval submissions Specific regulatory commitment section (like JNDA application form) Post Approval Management Plan appropriate to preclassify submission categories