Enforcement Actions. FDA Enforcement Options. Administrative tools I. Administrative Judicial Not undertaken lightly. Inspections Notice of violations

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1 Enforcement Actions FDA Enforcement Options Administrative Judicial Not undertaken lightly after Kirsten L. Vadheim, Ph.D., RAC & David A. Pettenski, Supervisory Investigator U.S. Food & Drug Administration 9May06 KLVadheim 1 9May06 KLVadheim 2 Administrative tools May begin at Center or Field office Often require Center concurrence Administrative tools I Inspections Notice of violations 483s NAI VAI OAI Untitled letters not subject to multiple layers of review Used when timeliness is critical Meetings 9May06 KLVadheim 3 9May06 KLVadheim 4

2 Administrative Tools II Warning letters most widely recognized titled letter FDA may initiate further enforcement action without additional correspondence formidable enforcement tool Warning letter issued when: Violations are of regulatory significance Voluntary action is expected Policy is unambiguous Failure to correct known problems requires further enforcement action It is deemed appropriate. 9May06 KLVadheim 5 9May06 KLVadheim 6 Warning letter is not issued when: There is a history of repeated violations no repeat warning letters Ripple Effects of Warning letter may include: Product reviews halted Violations are intentional and/or flagrant Reasonable possibility of injury or death Violations are Title 18 USC false statements conspiracy mail or wire fraud, etc 9May06 KLVadheim 7 Denial of export certifications Third-party consultant(s) may be required Foreign companies - FDA may issue import alert, closing US borders to the product 9May06 KLVadheim 8

3 Administrative tools III Administrative Tools IV Voluntary Corrective Programs Recalls Voluntary Mandatory Debarment Permanent Temporary (5 or 10 years) Civil Money Penalties 9May06 KLVadheim 9 9May06 KLVadheim 10 Administrative tools V Application Integrity Policy Delay, suspension and/or withdrawal of product applications Application Integrity Policy (AIP) Pattern or practice of wrongful conduct affecting the reliability of information in an application Requires (minimally) a thorough investigation by the company submission of a completely new application 9May06 KLVadheim 11 9May06 KLVadheim 12

4 Disqualification of Clinical Investigators Repeatedly or deliberately fails to comply with applicable regulatory requirements Repeatedly or deliberately submitted false information to the sponsor or FDA Listed on FDA website Debarment No ANDA, NDA, BLA NADA, ANADA, supplements or export applications allowed from debarred persons and/or companies Debarred person/company may not provide services in ANY capacity to a company holding an approved drug application Names published in FR and listed on FDA website 9May06 KLVadheim 13 9May06 KLVadheim 14 Additional Biologics Administrative tools Notice of Intent to Revoke (NOIR) License suspension License suspension Immediate withdrawal of authorization to ship a product in interstate commerce License revocation 9May06 KLVadheim 15 9May06 KLVadheim 16

5 License revocation Judicial Tools Cancellation of a license Seizure Withdrawal of authorization to ship a biologic in interstate commerce Does not require prior NOIR or suspension if willful misconduct has been established Injunction Prosecution (may result in debarment) 9May06 KLVadheim 17 9May06 KLVadheim 18 Judicial Tools II Most begin as Field recommendations Appropriate Center reviews/approves Usually subject to Office of Enforcement review Reviewed for sufficiency by Office of Chief Counsel Judicial Tools, II Some seizures, injunctions may require Dept. of Justice review All judicial actions subject to final review and approval by local US attorney 9May06 KLVadheim 19 9May06 KLVadheim 20

6 Seizure Civil action resulting in arrest of goods Injunction Civil action in which a federal court enjoins a company from violating federal law May be a specific lot of goods or a mass seizure GMP violations, e.g., entire warehouse of finished goods, raw materials and in-process products immediate effect: shuts down operations Chronic violations that have not responded to previous FDA efforts Immediate action required to address an imminent public health hazard (temporary restraining order) 9May06 KLVadheim 21 9May06 KLVadheim 22 Injunctions Temporary restraining order Consent Decree of Permanent Injunction Injunctions Prevent company from shipping products (or shipping only product specifically allowed by FDA) Complaint for permanent injunction Often requires 3rd party consultants Once granted, permanent injunctions can remain in effect forever Disgorgement fees Abbott - $100m in 1999 Schering Plough - $500m in May06 KLVadheim 23 9May06 KLVadheim 24

7 aside on Disgorgement Noncompliance penalties Alpharma & Perrigo FTC (price fixing) RxDepot (Denver) Canada imports Biogen-IDEC SEC (insider trading) Off-Label Promotion Year $$ 50M 430M Who Genentech Warner- Lambert rhgh What Gabapentin (False Claims Act) Assessment of additional financial penalties if enjoined company fails to meet FDA-mandated milestones E.g., $10,000 per day M Serono Somatropin (False Claims Act) M Lilly Raloxifen; initiated by AstreZeneca; + misdemeanor 9May06 KLVadheim 25 9May06 KLVadheim 26 Criminal Prosecution District Office Misdemeanor prosecutions rare Felony strict liability: an individual may be liable even if he/she did not consciously do wrong may result in debarment Investigators serve as eyes and ears for consumers Front-line Regulators Observe deficiencies/violations Obtain evidence Develop proof Samples, Photos, EIR s, Affidavits 9May06 KLVadheim 27 9May06 KLVadheim 28

8 District Office Centers - CDRH/CDER/CBER Determine significance of findings Recommend course of action Utilize direct reference authority (Discontinued) Determine appropriate Action of Choice Need for immediate Action *Administrative Detention Include documentation Well written EIR, Supporting documents, Necessary forms 9May06 KLVadheim 29 Recommendation received/assigned to compliance divisions within the centers Recommendations are: Reviewed for consistency with strategy/policy/precedent Reviewed for completeness and documentation Unless required, Centers do not review for direct reference issues 9May06 KLVadheim 30 Office of Enforcement (OE) Division of Case Management Operations (DCMO) Review case for completeness and consistency Review case for format and appropriateness Review case to assure FDA best interest Office of Chief Counsel Assigned to litigator Reviewed for legal sufficiency, appropriate format and support May contact witnesses to determine suitability Revise legal documents as necessary and in accord with jurisdiction 9May06 KLVadheim 31 9May06 KLVadheim 32

9 FDA Hdqts. Office District Office Dept. of Justice (DOJ) Inspection Supervisor Review Case Flow Compliance Officer Review Center Compliance Review CDRH/CDER/CBER Office of Chief Counsel (OCC) Legal Asst. U.S. Attorney (Seizures) Office of Enforcement (OE) Div Comp Mgt & Ops. (DCMO) Administrative Administrative Law Judge (ALJ) 9May06 KLVadheim 33 References ORA Compliance References: Regulatory Procedures Manual: Compliance Policy Guides: FDA Electronic FOIA Reading Room - Warning Letters: FDA Enforcement Activities: 9May06 KLVadheim 34 Summary It s easier to avoid trouble than to get out of trouble Questions? 9May06 KLVadheim 35 9May06 KLVadheim 36