1. 1 Process to Address Specifications for Delivered Dose Uniformity of Inhaled and Nasal Drug Products Presented by Robert O’Neill, Ph.D. Chair ACPS Working Group for DDU in OINDP 13 April 2004

2. 2 Proposal: Joint Working Group under ACPS FDA/IPAC-RS Working Group –Populated by senior representatives from FDA and OINDP industry –Defined Process Identified objectives Establish communication mechanism Defined timelines, milestones and resolution target date –Overall WG Objective: To agree on mutually acceptable PTIT test for DDU for OINDP

3. 3 Working Group Members Robert O’Neill, Ph.D. Chair (Director, Office of Biostatistics, Office of Pharmacoepidemiology and Statistical Science, CDER) Badrul Chowdhury, M.D., Ph.D. (Director, Division of Pulmonary Drug Products, Office of Drug Evaluation II, Office of New Drugs, CDER) Moheb Nasr, Ph.D. (Director, Office of New Drug Chemistry, CDER) Lawrence Yu, Ph.D. (Director for Science, Office of Generic Drugs) Michael Golden (Director, New Submissions North America, Global CMC Regulatory Affairs, GlaxoSmithKline) Kristi Griffiths, Ph.D. (Research Scientist, Global Statistical Sciences, Eli Lilly) Bo Olsson, Ph.D. (Scientific Adviser, Experimental Medicine, AstraZeneca) Dar Rosario (Director, Regulatory Affairs, Aradigm) Dennis Sandell, Ph.D. (Associate Principle Scientist, Analytical Development, AstraZeneca)

4. 4 Objective of the Working Group Develop a mutually acceptable, standard DDU specification (test and acceptance criteria) for OINDP with a proposal to ACPS in 2004

5. 5 Process Communication and Coordination –Communications Coordinated through Project Managers Agendas, minutes, meeting materials –Frequency of Meetings Monthly meetings at FDA, beginning in May 2004 May 2004 –Review ACPS Feedback –Identify technical expertise necessary to address »Statistical support »Clinical support »CMC support »Other –Technical Projects Leadership and project management for technical projects to assure resolution of issues in timely manner

6. 6 Process (cont.) Timelines and Milestones –Status report to ACPS in October 2004 –Submit recommendation to ACPS by end 2004

7. 7 Consensus Reached to Date Parametric tolerance interval approach is an improvement on current DDU test Concept requires refinement and further development to address regulatory requirements It is time to move forward and come to closure Working Group is formed to devote necessary resources and time to resolve (through data review and analysis, and development of appropriate statistical procedures)

8. 8 Issues where Consensus is Needed Better understanding the difference between operating characteristic (OC) curves (difference between FDA and IPAC- RS called “gap”) Evaluation of simulated performance and actual performance Zero tolerance criterion Statistical details of the test design Applicability to non-normal distributions

9. 9 Next Steps ACPS to endorse approach Working Group status report to ACPS in October 2004 Working Group to submit recommendation to ACPS by end 2004