Critical Path Initiative ONDC Perspective

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Critical Path InitiativeONDC Perspective

• John Simmons, Ph.D.
• Office of New Drug Chemistry
• Office of Pharmaceutical Science

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Outline

• Critical Path Initiative
• Current Regulatory Research
• Risk Based Initiatives
• Future Programs

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Critical Path Components
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Critical Path Components
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Critical Path Development
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Current ONDC Research

• Inefficient
• Reactive
• Unfocused
• Currently Developing New Paradigms Office
  Reorganization Review focus Research
  focus
• Seeking Input and Guidance

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Recent Regulatory Research Activities

• Conjugated Estrogens full characterization
  to establish criteria for pharmaceutical
  equivalence
• Prussian Blue establish the efficiency
  of in vitro Cs binding as an efficacy surrogate
  free Cyanide safety issue
• Inhalation Products develop in vitro
  methods to establish pharmaceutical equivalence
  - particle size, spray pattern, chemical imaging
• Drug Eluting Stents joint center
  guidance shortened critical path

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Conjugated Estrogens LC-ESI-MS Total Ion
Chromatogram
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m/z 349
estrone-3-sulfate
17a-dihydroequilin-3-sulfate
17ß-dihydroequilin-3-sulfate
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m/z 351
17a-estradiol-3-sulfate
17ß-estradiol-3-sulfate
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Risk-Based CMC Review

• Benefits of a Risk-Based System
• Patients
• Increased availability
• Faster approval of new products
• Continued supply of quality products
• FDA
• More product and process knowledge shared by
  industry
• More efficient resource allocation for review and
  inspection
• Increased trust and understanding in decision
  making

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Risk-Based CMC Review

• Benefits of a Risk-Based System
• Industry
• More efficient, science-based inspections
  resulting in increased consistency and process
  understanding
• Faster, more consistent reviews
• Potential for reduced regulatory burden
• Manage changes and nonconformance with less FDA
  oversight
• Focuses resources on critical issues
• Flexibility to focus on what should be done, not
  what can be done
• Improves communication with FDA

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Pharmaceutical QualityThe New Paradigm (JW)

• Need to examine and evaluate linkages between
• Quality attributes and clinical performance?
• Values/specifications and safety effectiveness?
• cGMP compliance and safety efficacy?
• Ultimate Goal The availability to the patient of
  high quality safe and effective drugs at
  reasonable cost

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The New Quality Assessment Paradigm

• CMC specifications to be based on
• Risk-based assessment
• Clinical Relevance
• Safety Considerations
• Process Capabilities
• Knowledge gained from Pharmaceutical Development
  Reports
• Better utilization of modern statistical
  methodologies
• Assessment starts with a comprehensive Quality
  Overall Summary (QOS)
• Review practices based on good scientific
  principles (cGSP)
• Increased emphasis on manufacturing science
• Peer/critical review of CMC evaluation by FDA
  scientists
• Integration of review and inspection

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Benefits of New Quality Assessment Paradigm
Less regulatory oversight for post-approval
changes
More incentive for continuous product improvement
Reengineered supplement review
More resources for new NDA review
Streamlined CMC review of resubmissions
Better and less expensive drugs to patients sooner
First cycle approval of new drugs
Risk-based quality assessment
QbD and PDR by applicant
Effective communication between FDA and applicant
Comprehensive QOS by applicant
Less review time
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Regulatory Future

• CMC only meetings with industry
• Quality by Design initiatives
• IND Guidances quality sections quality
  - safety linkage
• Process Analytical Technologies (PAT)
• Integration of Review-Inspection
• Strategies to facilitate 1st cycle approvals
• Combination Products
• Nano-particle drug products

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Next Steps

• Regulatory Issues PAT Guidance
  implementation CMC Guidance Revisions Combina
  tion Product Guidances Review-Inspection
  Integration

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Future Goals

• Establish a meaningful regulatory science program
  to support drug development and review
• Explore regulatory mechanisms to speed product
  approval