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 2

Consequences

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

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

Overall Process

• Inspection • Firm responses • Compliance Review • Changes in Status – Internal FDA review – Firm submissions – Reinspection 5

Six Systems Inspections

• Quality System – overarching • Facilities and Equipment System • Materials System • Production System • Packaging and Labeling System • Laboratory Control System 6

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

Standards

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

Issues

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

Legal Overview

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

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 11