Preparing the Quality Overall Summary in the New Paradigm

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Preparing the Quality Overall Summary in the
New Paradigm

• Michelle Herrera Foster, Ph.D.
• Regulatory Affairs Consultant
• CTD Quality Consulting

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Topics

• What is a Quality Overall Summary (QOS)
• Regulatory Evolution
• The New CMC Paradigm
• QOS as a Key Reviewer Tool
• QOS Pitfalls
• QOS Keys
• Conclusions

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ICH M4
NOT Part of the CTD
RegionalAdminInformation
Module 1
The CTD
QualityOverallSummary
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What is a QOS

• Summary of Module 3 (40-80 pages)
• Discussion of critical product attributes,
  critical manufacturing parameters
• Summary of key data, conclusions
• Content linked to Module 3
• Content integrated with other summaries
• Explanation of any guideline deviations

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A Summary of Module 3

• Module 3
• 3.2.S.1-.7, 3.2.P.1-.8,
• 3.2.A.1-.3, 3.2.R
• Detailed summaries
• Manufacturing
• Testing
• Characterization
• Pharm. Devt.
• Validation (reports)

• Module 2
• Same high level headings
• Key conclusions/data
• Flow chart, crit steps
• Specs, batch range
• Critical attributes
• Critical parameters
• Critical criteria

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Regulatory Origins of the Quality Overall Summary

• U.S. origin NDA CMC Summary
• EU origin Pharmaceutical Expert Report
• Japan origin GAIYO
• Required for all CTD submissions
• Required for all Marketing Applications (CTD) in
  Europe, Canada, Japan Canadian IND
• Required 1/08 for all eCTDs to CDER

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Regional Considerations for the Quality Overall
Summary

• US Comprehensive QOS
• US ANDA Question-Based Review
• FDAs GMP Initiative
• EU Critique of Design Space or PAT approach
• ICH Q8-Q9
• Canada Templates for phase 1-3, IND/NDS
• ICH initiative? TBD for harmonization

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The New CMC Paradigm

• GMP Initative Pharmaceutical Quality in the
  21st century gtgtgtgtgt Timely review and less
  supplements!
• Risk-based and science-based
• Process Analytical Technologies (PAT)
• Quality By Design (QbD) gt pre-defined quality
• ICH Q8 Pharmaceutical Development design
  space, critical attributes and parameters
• ICH Q9 - Quality Risk Management
• ANDAs Question-Based Review (QBR)

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The Comprehensive QOS

• Gives the reviewer an understanding of how the
  formulation and manufacturing process affects
  product quality and performance (safety and
  efficacy).
• Focuses on critical quality attributes (CQA) and
  critical manufacturing parameters
• Potentially a primary review document
• Being explored in FDAs CMC Pilot Program (see
  DIA 06-07 CMC Track Sessions)

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The QOS as a Key Reviewer Tool

• To expedite marketing approval
• CMC Development Plan, strategy
• Management approval of the bottom line
• Pre-meeting package
• Gap analysis
• Project management, Submission tracking
• Enhanced cross-functional communication

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QOS Pitfalls

• A dump of module 3 data - no value per FDA
  (Chi-Wu Chen, DIA06)
• No critical assessment
• Lack of rationales
• No integration with other summaries
• Just a regulatory requirement

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QOS Keys

• To help us
• Assist the preparation
• Facilitate review
• Expedite approval

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QOS Key 1Be Succinct

• High-level data summaries and conclusions
• Focus on key messages
• Focus on critical attributes and parameters
• Provide useful context
• Give the reviewers what they need to know to
  approve your product!

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QOS Key 2Bottom Line Up Front (BLUF)

• Conclusions First
• Dont make the reviewer wade through paragraphs
  to find out the bottom line
• Provide clear rationales supporting critical
  parameters and specifications
• Describe key issues and their resolutions
• Address key deviations from guidance
• Organize the information so that it is easy to
  follow and understand

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QOS Key 3Address key agency trends

• ICH Q8 Pharmaceutical Development, Quality by
  Design
• ICH Q9 Quality Risk Management
• Risk-based review
• Consider Question-Based Review, e.g. How was
  your product designed to have your defined
  critical attributes?

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QOS Key 4Link to Module 3

• Be consistent with module 3
• Cross-reference/hyperlink to module 3
• Make it easy for your reviewers to find the data
  supporting key messages in the Quality Overall
  Summary

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Conclusions

• The QOS is a key tool for agency review
• A well-written QOS could expedite approval
• The QOS can be the basis for internal CMC
  planning and tracking
• The QOS should assess risk and provide scientific
  rationales
• Be succinct and use BLUF
• Meeting the reviewers needs will help you meet
  your own needs, i.e. approval!
• Stay tuned for future QOS guidance

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Resources

• www.fda.gov
• www.emea.europa.eu/
• www.ich.org
• DIA Annual 06-07 CMC Track presentations
• Michelle Herrera Foster, Ph.D.
• 978-356-0872
• Michelle_at_ctdquality.com
• www.ctdquality.com