QbR: A Vision by Director of ONDQA FDA

1. Question-Based Review- A Vision
Ramesh Sood, Ph.D.
Division Director (Acting)
Office of New Drug Quality Assessment
24-Jan-2014
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2. Outline
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What is QbR
History
Potential benefits
Process
Feedback
Next steps
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3. What is QbR
• Question-based Review (QbR) is a general framework
for a science and risk-based assessment of product
quality
• Question-based review incorporates important scientific
and regulatory review questions
• ANDA/NDA applicants answer these questions in
module 2
• The quality reviewers evaluate the responses and body
of data in module 3 supporting applicant’s answers
• The questions apply to both new drug applications and
generic drug products
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4. What is QbR
• The questions are high level questions that address the
critical development aspects, product performance
aspects and manufacturing controls across dosage
forms
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Related to product design
Product performance
Risk to product performance
Control strategy
• A single set of questions that apply to both new drug
applications and generic drug products
• A checklist to capture noteworthy aspects of the
application
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5. QbR Elements
• No change to module 3
• The questions are formatted based on ICH M4 QOS
format resulting in minimal change for applicants
generating multi-region submissions
• Questions are located in Module 2, QOS
• A checklist to include noteworthy features of the
application (e.g., design space, formulation flexibility
etc.)
• A companion document with points to consider while
responding to each question on content
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6. History
• Currently being used by generic industry to
submit drug product information in ANDA
submissions
• QbR initiative started in year 2005 in Office of
Generic Drugs
• QbR fully implemented for generic drugs in year
2007
• Exploration of QbR for new drugs and for drug
substances initiated in year 2013 within FDA
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7. Benefits to Reviewers
• QbR approach streamlines the review
Guide to reviewers for consistent and
comprehensive quality evaluation
Determination of level of risk associated
with design, performance and manufacture
of the product
Puts on paper many of the internal
questions that a reviewer has while
reviewing the submission
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8. Benefits to Reviewers (contd.)
Reviewers spend time only documenting their
critical scientific assessment with rationale
Allows reviewers to conduct risk-based review
Little or no time spent on summarizing the
application
Provides consistency among the submissions
Leads to more focused and faster review
• OGD experienced improvement in the quality of
submissions
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9. Benefits to Applicants
• Provides clear indication to the applicant about the
reviewer’s expectations and concerns
– Provides transparency about the logic invoked by
reviewers
– A window to the reviewer’s concerns
• Provides opportunity to address critical questions about
the product’s design, performance, manufacturing
controls and risk of product failure both at the
performance and patient usability perspective
• Expected to lead to fewer questions from the reviewers
during the review cycle
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10. Process
• Used the current QbR questions from OGD as
the starting point
• NDA submissions were reviewed by OPS
reviewers with respect to the current OGD
questions
• Based on the gap analysis, a revised set of
questions was generated through collaboration
between OGD and ONDQA reviewers
• Additional NDAs are being reviewed based on
the new set of questions
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11. Initial Reviewer Feedback
• Leads to more focused and faster review
• Reviewers spend time only documenting critical
scientific assessment with rationale
• QbR questions shifted emphasis of assessment
to areas that were most likely to affect the quality
as it relates to product performance
• Standardized review enhances the quality of the
CMC evaluation
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12. Future Steps
• Gain more QbR implementation experience
among CDER reviewers
• Have a dialog with stakeholders (e.g., PhRMA)
and other regulatory agencies
• Refine questions based on reviewer and
industry feedback
• Seek industry volunteers for QbR submissions,
potentially through a pilot program
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13. Acknowledgements
• Dr. Lawrence Yu, Acting Director, OPS
• Dr. Christine Moore, Acting Director,
ONDQA
• QbR working group at FDA
• All of you for your attention
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14. Questions?
NewDrugCMC@fda.hhs.gov
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