Risk Based CMC Review Current Thinking - Overview

1
Risk Based CMC ReviewCurrent Thinking - Overview

• ACPS Meeting
• Oct. 21-22, 2003
• Yuan-yuan Chiu, Ph.D.
• OBP/OPS/CDER/ FDA

2
Overall Objective

• To incorporate scientific based risk-assessment
  and risk-management to CMC submission review
• Current thinking Intrinsically low risk drugs
• Expanded approach Focused on process
  understanding

3
Goal of Project 1

• To compile a list of drugs (low risk with respect
  to quality) that will qualify for
• the elimination of most of NDA/ANDA manufacturing
  supplements
• reduced CMC information needed to be submitted to
  an original ANDA (Truncated ANDA - TANDA) and AR
  to an approved NDA/ANDA/TANDA

4
Background

• Internal Discussion
• ACPS Meeting
• Scientific Workshop

• CMCCC CCC Scientific Rounds Brown bag
  meetings
• November, 2000 July, 2001, October, 2002
• AAPS Workshop - June, 2001
• DIA Annual Meeting - June, 2003

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A Three-Tier Process

• Tier 1
• Tier 2
• Tier 3

• 1A. To establish attributes and acceptance
  criteria
• 1B. To propose a drug list
• 2A. To finalize the drug list after medical
  consultation
• 2B. To eliminate supplements for most PAC, and
  to reduce data package to be submitted to AR
• 3. To determine a firms eligibility by
  evaluating its GMP compliance

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General Principleto Define Low Risk Drugs
Low

Probability of Detection
Medium
High
Low Risk
High
Low
Medium
Complexity
DS/DP characterization Mechanism of product
performance Manufacturing technology
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Members of Sub-working Groups Drug Substance
Drug Product

• Vilayat Sayeed
• Dan Boring
• Liang Zhou
• Sheldon Markofsky
• Davinder Gill
• Sung Kwang Kim

• Eric Duffy
• Paul Schwartz
• Marie Kowblansky
• Scott Furness
• Mayra Pineiro-Sanchez
• Haripada Sarker
• Rao Puttagunta