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Preparing the Quality Overall Summary in the New Paradigm

Preparing the Quality Overall Summary in the New Paradigm. Michelle Herrera Foster, Ph.D. Regulatory Affairs Consultant CTD Quality Consulting. Topics. What is a Quality Overall Summary (QOS) Regulatory Evolution The New CMC Paradigm QOS as a Key Reviewer Tool QOS Pitfalls QOS Keys

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Preparing the Quality Overall Summary in the New Paradigm

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  1. Preparing the Quality Overall Summary in the New Paradigm Michelle Herrera Foster, Ph.D. Regulatory Affairs Consultant CTD Quality Consulting

  2. 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

  3. Module 2 NonclinicalOverview ClinicalOverview NonclinicalSummary ClinicalSummary NonclinicalStudy Reports ClinicalStudy Reports Quality Module 3 Module 4 Module 5 ICH M4 NOT Part of the CTD RegionalAdminInformation Module 1 The CTD QualityOverallSummary

  4. 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

  5. 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 A Summary of Module 3

  6. 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

  7. Regional Considerations for the Quality Overall Summary • US: Comprehensive QOS • US: ANDA Question-Based Review • FDA’s 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

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

  9. 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 FDA’s CMC Pilot Program(see DIA ’06-07 CMC Track Sessions)

  10. 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

  11. QOS Pitfalls • A dump of module 3 data - “no value” per FDA (Chi-Wu Chen, DIA’06) • No critical assessment • Lack of rationales • No integration with other summaries • Just a regulatory requirement

  12. QOS Keys To help us: • Assist the preparation • Facilitate review • Expedite approval

  13. 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!

  14. QOS Key #2Bottom Line Up Front (BLUF) • Conclusions First • Don’t 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

  15. 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?”

  16. 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

  17. 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

  18. 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@ctdquality.com www.ctdquality.com

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