CTD Documents as Key Reviewer Tools

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CTD Documents as Key Reviewer Tools
Michelle Herrera Foster, Ph.D. Senior Regulatory
Consultant
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Objectives

• Explore how Common Technical Document (CTD)
  documents can serve as key reviewer tools, to
  meet the needs of the agency reviewers and
  internal reviewers
• Introduce key authoring tools and processes for
  submission-ready documents
• Present the CTD as a development tool

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ICH M4
NOT Part of the CTD
RegionalAdminInformation
Module 1
The CTD
QualityOverallSummary
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What do the Reviewers Need?

• Clear Conclusions
• Backed-up Justifications
• Risk Assessment
• Data summaries
• A framework for navigating the entire CTD
• Reasons to approve your drug
• Succinct, easy to review documents Summaries
  are key!

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CTD Summaries Module 2

• 2.3 The Quality Overall Summary
• 2.4 The Nonclinical Overview
• 2.5 The Nonclinical Summary
• 2.6 The Clinical Overview
• 2.7 The Clinical Summary

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Module 2 Summaries

• Summaries of Modules 3-5
• Content linked to Modules 3-5
• Summary of primary data, conclusions, rationales,
  and risk assessment
• Content of one summary integrated with the others
• Explanations of any guideline deviations

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2.3 Quality Overall Summary

• 40-80 pages
• 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
• Risk-based and science-based rationales (GMP
  Initiative, ICH Q8-10)

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2.4 Nonclinical Overview

• 30 pages
• Integrated critical assessment of the
  pharmacology, pharmacokinetics, and toxicology
  evaluations
• Addresses
• Adherence to guidance, justification of strategy
• GLP status
• Safety for intended clinical use
• Safety of impurities

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2.6 Nonclinical Written and Tabulated Summaries

• 100 150 pages
• Written summary of comprehensive factual synopsis
  of the nonclinical data
• Tabulated summaries using table formats in ICH M4
  Safety

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2.5 Clinical Overview

• 30 pages
• Critical analysis, succinct discussion, with
  conclusions and implications
• Addresses
• Strengths and limitations of study results
• Benefits and risks of the drug
• Support of prescribing information

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2.7 Clinical Summary

• 50 - 400 pages
• Detailed factual summarization of the clinical
  information
• Summarizes
• Individual clinical study reports
• Cross-study analyses
• Postmarketing data
• Table formats in ICH M4 Efficacy

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Pitfalls of Summaries

• A dump of module 3-5 data
• No critical assessment
• Lack of rationales
• No integration with other summaries
• Poor organization and presentation
• Just a regulatory requirement

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5 Keys for Summaries

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

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Key 1Be Succinct

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

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Key 2Provide Rationales

• Justify study designs, methodology, deviations,
  and acceptance criteria
• Reference agency agreements
• Conclusions must have a logic trail
• Dont wait for a deficiency question before
  providing justifications

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Key 3Bottom Line Up Front (BLUF)

• Conclusions First - Dont make the reviewer wade
  through paragraphs to find out the bottom line
• 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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Key 4Address key agency trends

• New guidance
• Recent approvals
• New technologies
• Risk-based review
• Consider Question-Based Review, e.g. How was
  your product designed to meet your defined
  critical attributes?

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Key 5Link to Modules 3-5

• Be consistent with modules 3-5
• Cross-reference and hyperlink to modules 3-5
• Make it easy for your reviewers to find the data
  supporting key messages in the summaries

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CTD Summaries asKey Reviewer Tools

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

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Key CTD Needs and Tools
Succinct, Key Messages CTD Summaries
Management Review CTD Summaries
Clinical to Marketing CTD-Ready Docs
Ease of authoring CTD Templates
Project Management CTD Mapping
Communication CTD Team
Lessons Learned CTD Team
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CTD-Ready Reports
Key results, conclusions
For QOS
Summary
Summary of methods
Module 3 data
Body of Report
Figures, graphs
Discussion
Raw data
Appendices
GMP Info
May not be submitted, on file
Protocols
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Conclusions

• CTD Summaries are key tools for agency review
• Summaries can be the basis for internal planning,
  review, and tracking
• Summaries should assess risk and provide
  scientific rationales
• CTD-ready documents enhance efficiency throughout
  development
• Meeting the reviewers needs will help you meet
  your own needs, i.e. approval!

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Speaker Contact

• Michelle_at_ctdquality.com
• 978-356-0872
• www.ctdquality.com