GMP Oversight Within FDAs Quality InitiativePast, Present, and Future

1
GMP Oversight Within FDAs Quality
InitiativePast, Present, and Future

• David J. Horowitz, Esq.
• Deputy Associate Commissioner for Compliance
  Policy
• Office Of Regulatory Affairs
• FDA/AAPS/ISPE Pharmaceutical Quality Initiatives
  Workshop
• March 1, 2007

2
Overview

• Why FDA launched the GMP Initiative
• Recent progress, whats next, and long term
  direction pertaining to inspections and GMPs
• Quality Systems
• Manufacturing Science and Technology
• Risk Management

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What Happened?

• In August, 2002, FDA launched a new initiative
  Pharmaceutical GMPs for the 21st Century A
  Risk-Based Approach.
• Called for a systematic re-appraisal of FDAs
  approaches to pharmaceutical product quality
  regulation.
• Involved ORA and all three pharmaceutical product
  Centers in FDA

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Why?

• Significant changes had occurred in the
  environment for pharmaceutical manufacturing
  since the cGMP program was put in place 25 years
  earlier.
• Challengesthat need to be addressed
• Opportunitiesthat can be realized

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Challenges

• Significant decline in resources for inspections
• Consequences of globalization, including more
  foreign manufacturing
• Greater complexity associated with manufacturing,
  including biotechnology

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Challenges (contd)

• Industry perception that GMP compliance was not
  adequately linked to public health protection
• FDA concern about the state of industry
  compliance and insufficient investment in
  manufacturing and quality systems

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Opportunities

• Major advances in manufacturing science and
  technology, including PAT
• Advances in quality management and
  systems-oriented approaches
• Advances in Risk Managementfor both industry and
  regulators

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Examples of ProgressQuality Systems

• External Quality Systems
• Final Guidancebridging GMP regulations to modern
  quality systems
• ICH Q10harmonizing quality systems approaches.

9
Examples of ProgressQuality Systems

• Internal (FDA) Quality Systems
• Enhanced communication between ORA and the
  Centers on pharmaceutical GMP warning letters
• Staff Manual Guide on quality systems framework
• Improved communication as a result of
  implementing Dispute Resolution Process

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Whats NextQuality Systems

• External
• ICH Q10
• Internal
• Quality systems implementation priorities
• PI, Warning letters, Recalls and enhanced
  collaboration between review and inspection
• ORA Transformation Initiative
• Imbed quality management systems throughout ORA
• Center collaboration effortswill help
  coordinate/harmonize Center/Field perspectives

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Whats NextQuality Systems (contd)

• Longer-Term
• Greater harmonization internationally, across
  organizational boundaries, and across product
  areas
• Enhanced integration of inspection with review
  and compliance perspectives

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Examples of ProgressScience Technology

• Creation of FDAs pharmaceutical inspectorate
  (PI)
• Includes enhanced technical training and
  certification
• Part 11 guidance
• Aseptic processing guidance
• Investigating OOS Test Results guidance
• Proposed rule and guidance on GMPs for Phase 1
  clinical supplies

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Whats NextScience Technology

• Ongoing training and certification for PI
• Part 11 rulemaking/guidance
• Process validation guidance
• Incremental approach to revising Parts 210/211,
  considering, as next step, clarification in areas
  of low hanging fruit, such as
• Potable water
• Aseptic processing
• Asbestos filters
• Verification by second individual
• Increased use and acceptance of PAT

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Whats NextScience Technology (contd)

• Longer-Term
• Greater specialization and expertise
• Enhanced collaboration with foreign regulatory
  counterpartsand across organizational boundaries
• Inspectional approaches that encourage adoption
  of latest scientific and technological
  innovations

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Examples of ProgressRisk Management

• ICH Q9, Quality Risk Managementinternationally
  harmonized guidance
• CDER risk ranking model for prioritizing sites
  for manufacturing inspections

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Whats NextRisk Management

• ORA Transformation
• Imbed risk-based approaches in all aspects of ORA
• CVM risk model for pre-and post-approval
  inspections
• Continual improvement of model for prioritizing
  GMP inspections
• Data quality enhancement
• Improved incentives to enhance process capability
• Use of risk factors to improve focus of
  inspections
• Improved dialog based on ICH Q9

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Whats NextRisk Management (contd)

• Longer-Term
• More systematic risk-based approaches relating to
  all aspects of GMP inspections
• Enhanced science- and data-driven targeting that
  will determine more of the inspection frequency
  and intensity, as well as FDAs response to the
  inspectional findings.
• Integration of more risk-based thinking from
  review to help focus inspections
• More outcome-oriented metrics will be developed

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Moving Ahead

• The same factors that motivated the initiative
  continue to drive it forward
• We recognized early on that we could not achieve
  our goals for the Initiative without active
  participation from our key stakeholders.
• Although were just getting started in some of
  the most important areas, we have a clear vision
  and significant momentum in several key areas