1. COMPLIANCE ACTIONS FDA Regulation & Licensure of Whole Blood & Blood Components, Including Source Plasma September 15-16, 2009 Helen Cowley Office of Compliance & Biologics Quality Division of Case Management Blood & Tissue Compliance Branch

2. DISCUSSION ITEMS Laws and regulations for biological products enforced by FDA Laws and regulations for biological products enforced by FDA Overview of compliance actions Overview of compliance actions Contact information for CBER, Office of Compliance & Biologics Quality Contact information for CBER, Office of Compliance & Biologics Quality

3. LAWS & REGULATIONS Federal Food, Drug & Cosmetic Act (FD&C) Federal Food, Drug & Cosmetic Act (FD&C) Public Health Service Act Public Health Service Act - Sections 351 & 361 Title 21, Code of Federal Regulations Title 21, Code of Federal Regulations - Parts 600-680; 210-211 - Parts 600-680; 210-211

4. INTERNAL REFERENCES Compliance Programs Compliance Programs –7342.001-Part V (Blood Banks) –7342.002-Part V (Source Plasma) Regulatory Procedures Manual Regulatory Procedures Manual –Chapters 4, 5 and 6

5. COMPLIANCE ACTIONS Regulatory tools used to bring firms that violate the laws FDA administers into compliance with those laws Regulatory tools used to bring firms that violate the laws FDA administers into compliance with those laws 3 types of actions: 3 types of actions: –Advisory –Administrative –Judicial

6. ADVISORY ACTIONS Written communication to notify a firm that a product, practices or other activities are in violation of the law Written communication to notify a firm that a product, practices or other activities are in violation of the law –Warning Letter –Untitled Letter

7. ADVISORY ACTIONS Warning Letters Violations cited are of regulatory significance Violations cited are of regulatory significance Action allows firms a chance to achieve voluntary compliance Action allows firms a chance to achieve voluntary compliance Corrections must be made promptly Corrections must be made promptly Serves as prior notice should FDA decide to take further action against a firm Serves as prior notice should FDA decide to take further action against a firm

8. ADVISORY ACTIONS New Initiative for Warning Letters Effective 08/10/2009, firms will have 15 working days to respond to a FDA-483 for possible mitigation of further action to be considered Effective 08/10/2009, firms will have 15 working days to respond to a FDA-483 for possible mitigation of further action to be considered FDA will follow-up issuance of a W/L with prompt and appropriate action to ensure compliance FDA will follow-up issuance of a W/L with prompt and appropriate action to ensure compliance Effective 09/01/2009, close-out letters will be issued to firms when FDA has verified that all violations identified in the W/L have been fully corrected Effective 09/01/2009, close-out letters will be issued to firms when FDA has verified that all violations identified in the W/L have been fully corrected

9. ADVISORY ACTIONS Untitled Letters Violations do not meet the threshold of regulatory significance for a Warning Letter Violations do not meet the threshold of regulatory significance for a Warning Letter Format of letter clearly distinguishes it from a Warning Letter Format of letter clearly distinguishes it from a Warning Letter

10. ADMINISTRATIVE ACTIONS License Suspension License Suspension License Revocation License Revocation

11. ADMINISTRATIVE ACTIONS License Suspension Provides for immediate withdrawal of the authorization to introduce biological products into interstate commerce Provides for immediate withdrawal of the authorization to introduce biological products into interstate commerce Conditions specified in 21 CFR 601.6 exist Conditions specified in 21 CFR 601.6 exist Grounds for revocation in 21 CFR 601.5 exist and there is a danger to health Grounds for revocation in 21 CFR 601.5 exist and there is a danger to health May be a step in the revocation process: May be a step in the revocation process: –may proceed to revocation –may hold revocation in abeyance pending resolution of issue

12. ADMINISTRATIVE ACTIONS License Suspension Examples of violations that might support a decision for license suspension: Examples of violations that might support a decision for license suspension: –Distribution of unsuitable products –Donor safety issues

13. ADMINISTRATIVE ACTIONS License Revocation Cancellation of a license and withdrawal of authorization to introduce or deliver for introduction biological products into interstate commerce Cancellation of a license and withdrawal of authorization to introduce or deliver for introduction biological products into interstate commerce Notice of Intent to Revoke Notice of Intent to Revoke –inspectional findings should include continuing violations –ordinarily requires prior notice via Warning Letter or meeting on these violations –offers an opportunity to achieve compliance Direct Revocation Direct Revocation –willful conduct must be established such as: - knowingly committing a prohibited act - acting with careless disregard of regulatory requirements –no opportunity to achieve compliance

14. ADMINISTRATIVE ACTIONS License Revocation Grounds for license revocation: Grounds for license revocation: –FDA unable to gain access to firm –Release of products not safe & effective for intended use –GMP deficiencies –Failure to notify CBER of significant manufacturing changes –Discontinuation of licensed product manufacturing

15. JUDICIAL ACTIONS Seizure Seizure Injunction Injunction Prosecution Prosecution

16. JUDICIAL ACTIONS Seizure Attachment of goods through a court order by a U.S. Marshal pursuant to Section 304 of the FD&C Act Attachment of goods through a court order by a U.S. Marshal pursuant to Section 304 of the FD&C Act United States is plaintiff United States is plaintiff Seized article or product is defendant Seized article or product is defendant

17. JUDICIAL ACTIONS Seizure Action of choice when FDA wants to remove violative products (adulterated or misbranded products) from distribution channels Action of choice when FDA wants to remove violative products (adulterated or misbranded products) from distribution channels Brought under FD&C Act Brought under FD&C Act Not the action of choice when removal involves short-dated products Not the action of choice when removal involves short-dated products

18. JUDICIAL ACTIONS Injunction A civil process initiated to stop or prevent a violation of the law and to correct the conditions that caused the violation to occur A civil process initiated to stop or prevent a violation of the law and to correct the conditions that caused the violation to occur

19. JUDICIAL ACTIONS Injunction To obtain an injunction, FDA must demonstrate: To obtain an injunction, FDA must demonstrate: –uncorrected deviations (prior warning) –violative activities which present a health hazard –a product or a component involved in its manufacture is shipped in interstate commerce

20. JUDICIAL ACTIONS Prosecution Institution of a criminal proceeding against an individual Institution of a criminal proceeding against an individual Authorization: Authorization: –U.S. Code 18 –U.S. Code 21 (FD&C Act) –U.S Code 42 (PHS Act)

21. JUDICIAL ACTIONS Prosecution Prosecution recommendations should contain criminal charges that show: Prosecution recommendations should contain criminal charges that show: – gross, flagrant or intentional violations, fraud or danger to health –a continuous or repeated course of violative conduct OCI (Office of Criminal Investigation) reviews all FDA matters for which a criminal investigation is recommended OCI (Office of Criminal Investigation) reviews all FDA matters for which a criminal investigation is recommended

22. CBER’s Office of Compliance & Biologics Quality OCBQ (Office of Compliance and Biologics Quality) OCBQ (Office of Compliance and Biologics Quality) –Mary Malarkey, Office Director DCM (Division of Case Management) DCM (Division of Case Management) –Robert Sausville, Division Director BTCB (Blood and Tissue Compliance Branch) BTCB (Blood and Tissue Compliance Branch) –Stephany Wesley, Branch Chief –Laura Hieronymous, Senior Recall Coordinator Contact phone # 301.827.6201 Contact phone # 301.827.6201