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

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

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

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

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

Process (cont.)

• Timelines and Milestones

– Status report to ACPS in October 2004

– Submit recommendation to ACPS by end 2004

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

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

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