COMPLIANCE ACTIONSCOMPLIANCE ACTIONS

FDA Regulation & Licensure of Whole Blood & FDA Regulation & Licensure of Whole Blood & Blood Components, Including Source PlasmaBlood Components, Including Source Plasma

September 15-16, 2009September 15-16, 2009

Helen CowleyHelen CowleyOffice of Compliance & Biologics QualityOffice of Compliance & Biologics QualityDivision of Case ManagementDivision of Case ManagementBlood & Tissue Compliance BranchBlood & Tissue Compliance Branch

DISCUSSION ITEMSDISCUSSION ITEMS

Laws and regulations for Laws and regulations for biological products enforced by biological products enforced by FDAFDA

Overview of compliance actionsOverview of compliance actions Contact information for CBER, Contact information for CBER,

Office of Compliance & Biologics Office of Compliance & Biologics Quality Quality

LAWS & REGULATIONSLAWS & REGULATIONS

Federal Food, Drug & Cosmetic Federal Food, Drug & Cosmetic Act (FD&C)Act (FD&C)

Public Health Service ActPublic Health Service Act- Sections 351 & 361- Sections 351 & 361

Title 21, Code of Federal Title 21, Code of Federal RegulationsRegulations

- Parts 600-680; 210-211- Parts 600-680; 210-211

INTERNAL REFERENCESINTERNAL REFERENCES

Compliance ProgramsCompliance Programs– 7342.001-Part V (Blood Banks)7342.001-Part V (Blood Banks)– 7342.002-Part V (Source Plasma)7342.002-Part V (Source Plasma)

Regulatory Procedures ManualRegulatory Procedures Manual– Chapters 4, 5 and 6Chapters 4, 5 and 6

COMPLIANCE ACTIONSCOMPLIANCE ACTIONS

Regulatory tools used to bring Regulatory tools used to bring firms that violate the laws FDA firms that violate the laws FDA administers into compliance with administers into compliance with those lawsthose laws

3 types of actions:3 types of actions:– AdvisoryAdvisory– AdministrativeAdministrative– JudicialJudicial

ADVISORY ACTIONSADVISORY ACTIONS

Written communication to notify Written communication to notify a firm that a product, practices a firm that a product, practices or other activities are in or other activities are in violation of the lawviolation of the law

– Warning LetterWarning Letter– Untitled LetterUntitled Letter

ADVISORY ACTIONS ADVISORY ACTIONS Warning Letters Warning Letters

Violations cited are of regulatory Violations cited are of regulatory significancesignificance

Action allows firms a chance to Action allows firms a chance to achieve voluntary complianceachieve voluntary compliance

Corrections must be made Corrections must be made promptlypromptly

Serves as prior notice should FDA Serves as prior notice should FDA decide to take further action decide to take further action against a firmagainst a firm

ADVISORY ACTIONS ADVISORY ACTIONS New Initiative for Warning New Initiative for Warning

LettersLetters Effective 08/10/2009, firms will have Effective 08/10/2009, firms will have

15 working days to respond to a FDA-15 working days to respond to a FDA-483 for possible mitigation of further 483 for possible mitigation of further action to be consideredaction to be considered

FDA will follow-up issuance of a W/L FDA will follow-up issuance of a W/L with prompt and appropriate action to with prompt and appropriate action to ensure compliance ensure compliance

Effective 09/01/2009, close-out letters Effective 09/01/2009, close-out letters will be issued to firms when FDA has will be issued to firms when FDA has verified that all violations identified in verified that all violations identified in the W/L have been fully corrected the W/L have been fully corrected

ADVISORY ACTIONSADVISORY ACTIONSUntitled LettersUntitled Letters

Violations do not meet the Violations do not meet the threshold of regulatory threshold of regulatory significance for a Warning Lettersignificance for a Warning Letter

Format of letter clearly Format of letter clearly distinguishes it from a Warning distinguishes it from a Warning LetterLetter

ADMINISTRATIVE ACTIONSADMINISTRATIVE ACTIONS

License SuspensionLicense Suspension License RevocationLicense Revocation

ADMINISTRATIVE ACTIONSADMINISTRATIVE ACTIONSLicense SuspensionLicense Suspension

Provides for immediate withdrawal of the Provides for immediate withdrawal of the authorization to introduce biological authorization to introduce biological products into interstate commerceproducts into interstate commerce

Conditions specified in 21 CFR 601.6 existConditions specified in 21 CFR 601.6 exist Grounds for revocation in 21 CFR 601.5 Grounds for revocation in 21 CFR 601.5

exist and there is a danger to healthexist 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 revocationmay proceed to revocation– may hold revocation in abeyance pending may hold revocation in abeyance pending

resolution of issue resolution of issue

ADMINISTRATIVE ADMINISTRATIVE ACTIONSACTIONS

License SuspensionLicense Suspension Examples of violations that might Examples of violations that might

support a decision for license support a decision for license suspension:suspension:– Distribution of unsuitable productsDistribution of unsuitable products– Donor safety issuesDonor safety issues

ADMINISTRATIVE ACTIONSADMINISTRATIVE ACTIONSLicense RevocationLicense Revocation

Cancellation of a license and withdrawal of Cancellation of a license and withdrawal of authorization to introduce or deliver for authorization to introduce or deliver for introduction biological products into interstate introduction biological products into interstate commercecommerce

Notice of Intent to Revoke Notice of Intent to Revoke – inspectional findings should include continuing inspectional findings should include continuing

violationsviolations– ordinarily requires prior notice via Warning Letter or ordinarily requires prior notice via Warning Letter or

meeting on these violationsmeeting on these violations– offers an opportunity to achieve complianceoffers an opportunity to achieve compliance

Direct Revocation Direct Revocation – willful conduct must be established such as:willful conduct must be established such as:

- knowingly committing a prohibited act - knowingly committing a prohibited act - acting with careless disregard of regulatory requirements - acting with careless disregard of regulatory requirements

– no opportunity to achieve complianceno opportunity to achieve compliance

ADMINISTRATIVE ACTIONSADMINISTRATIVE ACTIONSLicense RevocationLicense Revocation

Grounds for license revocation:Grounds for license revocation:– FDA unable to gain access to firmFDA unable to gain access to firm– Release of products not safe & Release of products not safe &

effective for intended useeffective for intended use– GMP deficiencies GMP deficiencies – Failure to notify CBER of significant Failure to notify CBER of significant

manufacturing changesmanufacturing changes– Discontinuation of licensed product Discontinuation of licensed product

manufacturingmanufacturing

JUDICIAL ACTIONSJUDICIAL ACTIONS

SeizureSeizure InjunctionInjunction ProsecutionProsecution

JUDICIAL ACTIONSJUDICIAL ACTIONSSeizureSeizure

Attachment of goods through a Attachment of goods through a court order by a U.S. Marshal court order by a U.S. Marshal pursuant to Section 304 of the pursuant to Section 304 of the FD&C ActFD&C Act

United States is plaintiffUnited States is plaintiff Seized article or product is Seized article or product is

defendantdefendant

JUDICIAL ACTIONSJUDICIAL ACTIONSSeizureSeizure

Action of choice when FDA wants to Action of choice when FDA wants to remove violative products remove violative products (adulterated or misbranded (adulterated or misbranded products) from distribution channelsproducts) from distribution channels

Brought under FD&C ActBrought under FD&C Act Not the action of choice when Not the action of choice when

removal involves short-dated removal involves short-dated productsproducts

JUDICIAL ACTIONSJUDICIAL ACTIONSInjunctionInjunction

A civil process initiated to stop or A civil process initiated to stop or prevent a violation of the law and prevent a violation of the law and to correct the conditions that to correct the conditions that caused the violation to occurcaused the violation to occur

JUDICIAL ACTIONSJUDICIAL ACTIONSInjunctionInjunction

To obtain an injunction, FDA must To obtain an injunction, FDA must demonstrate:demonstrate:– uncorrected deviations (prior uncorrected deviations (prior

warning)warning)– violative activities which present a violative activities which present a

health hazardhealth hazard– a product or a component involved in a product or a component involved in

its manufacture is shipped in its manufacture is shipped in interstate commerce interstate commerce

JUDICIAL ACTIONSJUDICIAL ACTIONSProsecutionProsecution

Institution of a criminal Institution of a criminal proceeding against an individualproceeding against an individual

Authorization:Authorization:– U.S. Code 18U.S. Code 18– U.S. Code 21 (FD&C Act)U.S. Code 21 (FD&C Act)– U.S Code 42 (PHS Act)U.S Code 42 (PHS Act)

JUDICIAL ACTIONSJUDICIAL ACTIONSProsecutionProsecution

Prosecution recommendations should Prosecution recommendations should contain criminal charges that show:contain criminal charges that show:– gross, flagrant or intentional violations, gross, flagrant or intentional violations,

fraud or danger to healthfraud or danger to health– a continuous or repeated course of a continuous or repeated course of

violative conductviolative conduct OCI (Office of Criminal Investigation) OCI (Office of Criminal Investigation)

reviews all FDA matters for which a reviews all FDA matters for which a criminal investigation is criminal investigation is recommendedrecommended

CBER’s Office of Compliance CBER’s Office of Compliance & Biologics Quality& Biologics Quality

OCBQ (Office of Compliance and Biologics OCBQ (Office of Compliance and Biologics Quality)Quality)– Mary Malarkey, Office DirectorMary Malarkey, Office Director

DCM (Division of Case Management)DCM (Division of Case Management)– Robert Sausville, Division DirectorRobert Sausville, Division Director

BTCB (Blood and Tissue Compliance Branch)BTCB (Blood and Tissue Compliance Branch)– Stephany Wesley, Branch ChiefStephany Wesley, Branch Chief– Laura Hieronymous, Senior Recall CoordinatorLaura Hieronymous, Senior Recall Coordinator

Contact phone # 301.827.6201Contact phone # 301.827.6201