1. Organizational Gaps in Reaching the “Desired State” Helen Winkle

2. OPS Organization Office of Pharmaceutical Science Helen N. Winkle, Director Ajaz S. Hussain, Ph.D., Deputy Office of Biotechnology Products Keith Webber, Ph.D. Office of Generic Drugs Gary Buehler Office of New Drug Chemistry Moheb M. Nasr, Ph.D. Office of Testing and Research Ajaz Hussain, Ph.D. Div. of Monoclonal Antibodies Steven Kozlowski, M.D. Div. of Therapeutic Proteins Amy Rosenberg, M.D. Div. of Bioequivalence Dale Conner, Pharm.D. Div. of Chemistry I Rashmikant Patel, Ph.D. Div. of Chemistry II Florence Fang Div. of Labeling and Program Support Peter Rickman Div. of Chemistry III Vilayat Sayeed, Ph.D. Div. of New Drug Chemistry I John Simmons, Ph.D. Div. of New Drug Chemistry II Eric Duffy, Ph.D. Div. of New Drug Chemistry III David Lin, Ph.D. Lab. of Clinical Pharmacology Jerry Collins, Ph.D. Div. of Applied Pharmacology Research Jerry Collins, Ph.D. Div. of Pharmaceutical Analysis Lucinda Buhse, Ph.D. Div. of Product Quality Research Robbe Lyon, Ph.D. New Drug Microbiology Team Informatic Computational Safety Analysis Process Analytical Technologies

3. Organizational Gaps Multi-dimensional Between organizations Within organizations Outside of OPS - other parts of CDER organization Organizational gap is what we need to consider and “resolve” within our process before we can adequately implement regulatory direction and support (through applications process and review) of the “desired state”

4. What Constitutes the Gap in OPS? Appropriate utilization and focus of available human resources Difference in products and regulatory requirements and review processes Organizational structure - lack of consistency and flexibility Process driven, not science driven –PDUFA –First in - first reviewed –Heavy workloads/Backlogs –Too many supplements Interaction with inspection - lack of appropriate reviewer involvement - don’t get feedback

5. What Constitutes Gap? Possibility of two-tiered system - how do you handle? Guidances to accomplish consistency - sometimes too prescriptive Organizational components too reactive not proactive (caused by workload - perpetuates problem) Use of available scientific expertise and scientific collaboration Challenge of focusing on appropriate questions (based on information received) Lack of utilization of appropriate tools (e.g., statistics) Lack of good communication between disciplines

6. Closing the Gap Structural changes needed in some parts of organization Reviewers on inspections or as consultants to inspections so have complete knowledge on product Answering questions regarding manufacturing science and review including whether or not have QOS, what need in way of pharmaceutical development information, how does industry determine critical attributes, etc., and how we will review

7. Closing the Gap Better understanding of what constitutes design space across all products and when notification to FDA of change in manufacturing is warranted Understanding of what constitutes risk for a product - development of a systematic risk-based approach to review processes Guidances Training Determining process for working under a “two-tiered” system Developing an internal system for handling differences in review decisions Appropriate metrics

8. Current Steps Across OPS –Working group under Manufacturing Subcommittee of ACPS to address questions –ICH participation –Workshop on specification setting - March 2005 - broad scope –Collaboration with academics and PQRI –Internal review of current guidance –Developing a program for team interactions for inspections –Training for reviewers (scientific seminars, etc.) –Formation of OPSCC –Finish guidance on comparability protocol

9. Current Steps ONDC –Changing to an assessment program focused on quality attributes (chemistry, pharmaceutical formulation and manufacturing processes) –New organization structure (independent discipline) –Proposed QOS –Team approach –Establishing a peer review process –Implementing quality systems approach –Developing a mock NDA –Reducing supplement requirements OBP beginning to identify where can reduce supplements

10. Current Steps OGD –Reorganization - additional chemistry division –Change in supplement review and evaluation to determine if some supplements can be eliminated –Team approach - better application of scientific expertise and consistency –Efficiencies in review - eliminating redundant or non-essential review activities OBP –Review of supplement requirements to determine where can eliminate or reduce

11. Additional Steps Involve stakeholders in review of guidances, answering manufacturing science issues, etc. Determine how to handle a “two-tiered” approach - if at all Hold additional external workshops (e.g, QOS) Develop a dispute resolution process Review how handle PAI process Develop appropriate metrics Other?

12. Observations and Conclusions Need to continue to address organizational gap issues Culture is an important element of change management Will take time!! Depends on resolving some of the science gaps Need to include stakeholders in making some of the decisions and developing some of the procedures Training of reviewers important!! Will identify more steps as move forward