Quality by Design

1
Quality by Design Question-Based Review
Observations by the Generic Pharmaceutical
Industry

• Advisory Committee for Pharmaceutical Science
• October 5, 2006
• Gordon Johnston
• Generic Pharmaceutical Association

2
Outline

• Introduction
• Quality by Design
• Question-Based Review
• Summary

3
Introduction

• QbD/QbR
• Requires significant changes to cross-functional
  coordination within firms
• Shift to QbR content represents a major change
• Cautiously optimistic
• A steep learning curve for industry
• Conversion to CTD format
• Aggressive implementation schedule by FDA
• 800 ANDAs expected in CY 2006
• Increased burden for industry

4
Quality by Design

• Extensive manufacturing expertise in the industry
• Generic firms often manufacture 50 - gt100
  products
• Product and process understanding is critical for
  efficiency
• Concepts of QbD have been in use by industry for
  many years
• QbD represents a more organized and integrated
  approach to product development

5
Quality by Design

• Opportunities
• Value in prior knowledge
• Extensive experience with common formulations
• Excipient properties well understood
• Critical attributes impacting manufacturing
  process known

6
Quality by Design

• Opportunities (contd)
• Keen knowledge of equipment and common
  manufacturing processes
• Blending, coating, etc.
• Potential for reduced review time
• Potential for reduced post-approval burden

7
Quality by Design

• Are QbD expectations clearly defined?
• GMP implications?
• Experience to date is mixed
• ICH Q8 concepts still being integrated by Field
• Field often expects full design space validation
• Prior knowledge not universally accepted by
  investigators at this time

8
Quality by Design

• Should FDA modify its focus?
• Generic industry still required to accept FDA
  dissolution specifications
• Continued requirements to set specifications
  typically based on process capabilities and not
  product performance
• For example, residual solvents
• More guidance on non-oral dosage forms needed

9
Question-Based Review

• Represents a tool to efficiently assess QbD
  approach
• Industry is supportive of the initiative
• Industry and OGD still learning

10
Question-Based Review

• OGD Model QOS
• 2 years in the making
• Open dialogue between OGD and generic industry
  during evolution
• OGD responsive to QA sessions

11
Question-Based Review

• OGD Model QOS
• OGD-industry collaboration has accelerated
  industrys understanding of QbR
• Ongoing communication critical during full
  implementation

12
Question-Based Review

• OGD Model QOSs
• Help industry recognize issues OGD generally
  considers critical
• Guide industry toward quality by design
• Assist industry to prepare a high quality QOS

13
Question-Based Review

• OGD Questions
• Allow industry to address some questions with
  prior knowledge
• Industry has been active in submitting QbR
  applications
• Over 35 ANDAs
• First ANDA Approval last month

14
Question-Based Review

• Challenges
• Simultaneous conversion to CTD format and QBR
  data elements
• Implementation schedule has been challenging for
  some companies
• Some companies have been submitting QbR
  applications since this summer
• Substantial internal training and coordination
  required for implementation

15
Question-Based Review

• Challenges
• Still uncertain on OGD expectations for QOS and
  product development reports
• Oct 20 OGD training on how to prepare a high
  quality QOS
• Initial response is very positive
• More OGD training if needed

16
Question-Based Review

• Recommendation
• Post-approval reduction in regulatory burden?
• Industry requests clarity on types of supplements
  where regulatory burden may be downgraded
• Extending QbR concept to already approved
  products (gt8000)?
• Extending QbR concept to drug substance DMF

17
Summary

• Excellent communications by OGD
• Numerous meetings, webcasts, teleconferences
  during development phase of QbR
• Ongoing industry-OGD communications critical
• Increased burden

18
Summary

• Need to expand QbR to already approved ANDAs and
  drug substance DMF
• Post-approval regulatory relief a critical
  outcome of initiative
• Industry remains cooperative and hopeful
• Reassess in a year