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Question-Based Review- A Vision

Ramesh Sood, Ph.D.Division Director (Acting)

Office of New Drug Quality Assessment24-Jan-2014

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Outline

• What is QbR• History• Potential benefits• Process• Feedback• Next steps

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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

What is QbR

• The questions are high level questions that address the critical development aspects, product performance aspects and manufacturing controls across dosage forms– 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 4

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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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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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Benefits to Reviewers

• QbR approach streamlines the reviewGuide to reviewers for consistent and

comprehensive quality evaluationDetermination 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

Benefits to Reviewers (contd.)Reviewers spend time only documenting their

critical scientific assessment with rationaleAllows reviewers to conduct risk-based reviewLittle or no time spent on summarizing the

application Provides consistency among the submissionsLeads to more focused and faster review

• OGD experienced improvement in the quality of submissions

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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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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 10

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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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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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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Questions?

NewDrugCMC@fda.hhs.gov