FDAs Pharmaceutical Quality Initiatives Implementation of a Modern Riskbased Approach

1
FDAs Pharmaceutical Quality Initiatives
Implementation of a Modern Risk-based Approach

• Co-sponsored with AAPS and ISPE
• February 28, to March 2, 2007

Question-based Review (QbR) Initiative - Office
of Generic Drugs
Frank O. Holcombe, Jr. Ph.D. Associate Director
for Chemistry Office of Generic Drugs / OPS / CDER
2
Quality Assessment

• Quality Assessment refers to the review of a drug
  product submission and the evaluation made
  regarding the approval of that submission

3
Quality Assessment

• Assessment of Application Content
• Appropriate information (topic)
• Relevant information (support)
• Complete information (extent)

4
Quality Assessment

• Pharmaceutical Quality in 21st Century
• Quality achieved through design
• Understanding of factors affecting product
  performance
• Capacity for continuous improvement
• Regulatory policy based on product understanding
• Risk-based environment

5
Quality by Design (QbD)

• Quality-by-Design
• Define target product quality profile
• Performance needed to obtain clinical benefit and
  meet consumer expectation
• Design and develop product and manufacturing
  process to meet target quality profile
• Critical product quality attributes
• Identify and control critical raw material
  attributes, parameters, and sources of
  variability
• Monitor and update the process to assure
  consistent quality over time

6
Quality Assessment

• Application Content
• Appropriate information (topic)
• Relevant information (support)
• Complete information (extent)
• Demonstration of understanding factors that
  affect product performance

7
Question Based Review

• Drivers for change
• Application
• Variable content quality and information
• Primarily data submission often no summary or
  discussion
• Generally not applicable to current goal
• Administrative
• Multiple review cycles
• Resources

8
Question Based Review

• Question-based-review (QbR)
• Utilizes an outline of issues important in
  addressing QbD elements
• Outline structured as series of questions
• Questions have area/topic focus
• Submissions encouraged in CTD format
• Utilizes CTD Module 2 Quality Overall Summary for
  introduction to pertinent issues

9
Question Based Review

• Expectations
• Firms use questions as context for product
  quality demonstration
• Use of QbD focus and Section P.2. to provide
  additional emphasis on development and
  justification
• More transparency in rationale for product
  criteria
• Through P.2., better understanding of issues
  affecting product quality
• Increased understanding of areas of risk to
  product quality

10
Question Based Review

• Models posted on OGD website
• Immediate release, modified release solid oral
  products
• Examples in context of CTD Module 2 Summary
• www.fda.gov/cder/ogd/QbR.htm

11
Question Based Review

• Experience
• Approximately 100 applications since July 2006
• Benefits
• Advantages in review document preparation
• Additional insight into development
• Additional justification for criteria
• Explicit identification of critical parameters

12
Question Based Review

• Challenges
• Variable implementation
• Product development data
• Process data
• Materials compatibility
• Justification of product specification
• Old information in new format
• Use of Model as submission, not as example

13
Question Based Review

• Development - 2005 to date
• Reviewer and Review Management input
• Industry and Trade Organization input
• Training
• Internal
• External
• QOS example presentations

14
Question Based Review

• The QbR Initiative is NOT
• Defining QbD
• A checklist for application approval
• The QbR Initiative IS
• A tool for more efficient, effective,
  science-based pharmaceutical quality assessment
  of generic drug applications