1. FDA Facility Evaluation Douglas Stearn Deputy Director for Policy and Analysis Office of Compliance Center for Drug Evaluation and Research

2. 2 FDA Categories OAI -- Official Action Indicated VAI – Voluntary Action Indicated NAI – No Action Indicated

3. Consequences Potential Enforcement –Warning letters –Seizure, injunction, prosecution –Import alert Approval status Market consequences 3

4. 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 4

5. 5 Overall Process Inspection Firm responses Compliance Review Changes in Status – Internal FDA review – Firm submissions – Reinspection

6. Six Systems Inspections Quality System – overarching Facilities and Equipment System Materials System Production System Packaging and Labeling System Laboratory Control System 6

7. 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 7

8. 8 Standards Toward principles and consistency CGMP Interpretations and applications –Guidance –Warning letters

9. 9 Issues Materiality Scope of problems and remedial fit Supply chain oversight –Contract manufacturers –Component manufacturers Red flags

10. 10 Legal Overview FDCA -- generally remedial Subject matter expertise matters Legal standing issues Deference to FDA and its limits Legal interpretation Technical expertise

11. 11 The Likely Future of FDA Facility Evalutions Metrics and Standards Development More objectivity More looks across company and industry FDASIA 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