Transcript Slides
FDA Facility Evaluation
Douglas Stearn
Deputy Director for Policy and Analysis
Office of Compliance
Center for Drug Evaluation and Research
FDA Categories
• OAI -- Official Action Indicated
• VAI – Voluntary Action Indicated
• NAI – No Action Indicated
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Consequences
• Potential Enforcement
– Warning letters
– Seizure, injunction, prosecution
– Import alert
• Approval status
• Market consequences
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Why Inspect?
• Preapproval review includes CGMP
(21 U.S.C. 355(d)(3))
• Other “for cause” inspections – includes
complaints, informants, follow-up
• Surveillance inspections
– Risk model
– Inspection planning
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Overall Process
• Inspection
• Firm responses
• Compliance Review
• Changes in Status
– Internal FDA review
– Firm submissions
– Reinspection
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Six Systems Inspections
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Quality System – overarching
Facilities and Equipment System
Materials System
Production System
Packaging and Labeling System
Laboratory Control System
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Common Significant Observations
• Patterns of failure
– To document or review operations & changes
– To conduct adequate investigations
– To resolve discrepancies or complaints
– To conduct testing and conform to controls
• Contamination – real and potential
• Data integrity – hardest thing to fix
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Standards
• Toward principles and consistency
• CGMP
• Interpretations and applications
– Guidance
– Warning letters
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Issues
• Materiality
• Scope of problems and remedial fit
• Supply chain oversight
– Contract manufacturers
– Component manufacturers
• Red flags
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Legal Overview
FDCA -- generally remedial
Subject matter expertise matters
Legal standing issues
Deference to FDA and its limits
• Legal interpretation
• Technical expertise
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The Likely Future of FDA Facility
Evalutions
Metrics and Standards Development
• More objectivity
• More looks across company and industry
FDASIA
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Section 705 – risk-based frequency
Section 706 – records requests
Section 712 – use foreign regulator inspections
More risk-based time frames for evaluation
GDUFA – movement to surveillance
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