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Establishment Submissions

Rosia E. Nesbitt, BS, SBB(ASCP), CQA(ASQ)Consumer Safety Officer

CBER, OBRR, DBA

September 15, 2009

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Outline• Mergers

• What to Submit for Mergers

• Acquisitions

• Acquisitions Licensed Buyer

• What to Submit for Acquisitions by a Licensed Buyer

• Acquisitions by an Unlicensed Buyer

• What to Submit for Acquisitions by an Unlicensed Buyer

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Outline (cont.)

• Manufacturer Reducing Operations

• What to Submit for Manufacturer Reducing Operations

• Manufacturer Revoking All Locations

• Facility Moves

• Product Testing Laboratory Relocation

• Legal Name Change

• What to Submit for legal name change

• References

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Mergers

• Union of two or more licensed manufacturers to form a new legal entity

• Requires issuance of a new U.S. License

• New Submission Tracking Number

• Should be reported as a Prior Approval Supplement under 601.12(b)

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Mergers (cont.)

• All records, including donor deferral registries, should be part of the operational records

• Source Plasma (SP) facilities may utilize previously approved physician substitute programs

• Approval does not relieve or exempt manufacture from any or all obligations arising from:

– Outstanding inspectional issues

– Compliance issues relating to operations at acquired facilities

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What to Submit for Mergers

• Submit Form FDA 356h

• The new U. S. License holder should submit a cover letter which addresses the following:

– Managerial structure, including Authorized Official

– Reporting responsibilities

– QA oversight

– Any changes to the physical plant or equipment and/or manufacturing procedures

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What to Submit for Mergers (cont.)

• Major equipment list should include:

–Computer system and associated software (manufacturer, model, version number)

–Apheresis equipment

–Blood irradiators

– Infectious disease testing instrumentation

–Self-contained mobile collection units

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What to Submit for Mergers (cont.)

• Major equipment list should not include the following:

– Computer peripherals such as printers, label printers, terminals

– Personal Computers (PC)

– Laboratory testing equipment other than infectious disease testing instrumentation

– General laboratory centrifuges

– Refrigerators, freezers or other temperature and humidity control storage systems

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What to Submit for Mergers (cont.)

• List of licensed blood and blood components

– Should include detailed information regarding the manufacture of each licensed product in the applicant’s facility or facilities

– Approvals may be “site-specific”

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What to Submit for Mergers (cont.)

• List of approved SOPs

• Updated Form FDA 2830 or update registration on the FDA website

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What to Submit for Mergers (cont.)

• Submit draft Labels with Form FDA 2567

• Submit Circular of Information (not required with SP facilities)

• Submit final printed labels for each product showing applicant’s name, address and license number once approved

– Should be completed and submitted within 180 days of receipt of approval letter

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Acquisitions• An acquisition occurs when one U.S. License holder

purchases a facility that was previously operating under a different U.S. License

• The acquired facility will no longer be connected to the original U.S. License number

• The license of the previous U.S. license holder will be revised to remove the facility (revoked)

• The license of the U.S. holder acquiring the facility will be supplemented to include the acquired facility

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Acquisitions (cont.)

• Approval does not relieve or exempt the manufacturer from any or all obligations arising from:

– Outstanding inspectional issues

– Compliance issues relating to operations at acquired facilities

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Acquisitions by a Licensed Buyer

• U. S. license holder who expands their operations to include manufacturing at additional locations

• Facilities may be acquired from manufacturers who are either reducing operations to fewer locations or permanently closing all locations

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Acquisitions by a Licensed Buyer (cont.)

• The licensed buyer acquiring facilities should:

– Include a statement that describes how the new facility will be incorporated into their manufacturing organization

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Acquisitions by a Licensed Buyer (cont.)

• The licensed buyer should address:

– SOPs to be used at acquired facility

– Changes in core staff or major equipment

– Disposition of product remaining at facility which were collected under previous U.S. License

– Responsibility for donor deferral

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Acquisitions by a Licensed Buyer (cont.)

– SOPs should contain steps for obtaining information on previous donations if lookback is required

– Any changes in contracting facilities (e.g., outside testing laboratory, offsite storage facility etc.)

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Acquisitions by a Licensed Buyer (cont.)

• All approvals previously in place at the acquired centers will be applied to new owner

• Approvals are specific for the individual centers

• Practices approved at a specific center can now be performed by the new owner

• All manufacturing records from the previous owner will be retained as part of the newly acquired facility’s operational record

– Including donor deferral registries

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What to Submit for Acquisitions by a Licensed Buyer

• If the new owner wants the approvals from one center to be applied to other centers, they must submit a supplement

• Updated Form FDA 2830 or update registration on the FDA website

• Labels and Form FDA 2567, if applicable

• Submit as a CBE30

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Acquisitions by an Unlicensed Buyer Not All Facilities Acquired

• An acquisition may occur when an applicant who currently holds no U.S. license

– Purchases some but not all facilities that were previously operating under one U.S. license

• The new owner must apply to be licensed as a new applicant (BLA) [21 CFR 601.2]

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Acquisitions by an Unlicensed Buyer All Facilities Acquired

• An acquisition may also occur when an applicant who currently holds no U.S. license

– Purchases all facilities that were previously operating under one U.S. license

• The new owner must apply to be licensed as a new applicant (BLA) [21 CFR 601.2]

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Acquisitions by an Unlicensed BuyerGeneral Information

• Cannot distribute products under new license until approved

• When all facilities are purchased, the license of the previous U.S. license holder will be revoked

• When some facilities are purchased, the license of the previous U.S. license holder will be revised to remove the facilities that were sold

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Acquisitions by an Unlicensed Buyer (cont.)

• Approval does not relieve or exempt manufacture from any or all obligations arising from:

– Outstanding inspectional issues

– Compliance issues relating to operations at acquired facilities

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What to Submit for Acquisitions by an Unlicensed Buyer

• Form FDA 356h

• List acquired locations; include addresses and registration numbers

• For contractors: submit name, address, registration number (e.g. outside testing laboratory (OTL), offsite storage facility)

• Include tests the OTL will perform

• Form FDA 2567 with Labels

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What to Submit for Acquisitions by an Unlicensed Buyer (cont.)

• All manufacturing records from the previous owner will be retained as part of the newly acquired facility’s operational record

– Including donor deferral registries

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What to Submit for Acquisitions by an Unlicensed Buyer (cont.)

• State if products will continue to be prepared using the previous company’s approved SOPs, major equipment, and core personnel

• Submit:– New or previously approved SOPs

• SOPs should contain steps for obtaining information on previous donations if lookback is required

– Major equipment list

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Manufacturer Reducing Operations

• Revoking some but not all manufacturing facilities in order to operate at fewer locations

• Some locations will be sold or permanently closed

• Manufacturer will retain its U.S. License

• U.S. license will be revised to remove facilities that were either permanently closed or sold

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Manufacturer Reducing OperationsWhat to Submit

• List of facilities that are permanently closing or being sold with their registration numbers

• Name, address, registration number and license number of buyer

• Date of potential sale

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Manufacturer Revoking All Locations

• All locations will be sold or permanently closed

• List of locations that are permanently closing or being sold with their registration numbers

• Name and address of buyer and date of potential sale, if being sold

• Manufacturer’s U.S. License revoked

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Facility Moves – Temporary Closures

• Facility moves that require temporary closure so new staff can be hired prior to reopening

– Change is analogous to opening an additional facility under the same license

• Submit as a PAS

• Requires a pre-approval inspection

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Facility Moves – Multiple Changes• Relocation of a major manufacturing facility

– Core personnel changes, e.g., center management, medical personnel

– SOPs and/or major equipment changes

• Submit as a Prior Approval Supplement (PAS)

• Submit Form FDA 2830 or update registration on the FDA website

– Within 5 days of the change (607.26)

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Facility Moves – Personnel Changes• Relocation of a major manufacturing facility

– No changes in SOPs and major equipment

– Core personnel changes, e.g., center management, medical personnel

• Submit as a PAS

• Submit updated Form FDA 2830 or update registration on the FDA website

– Within 5 days of the change (607.26)

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Facility Moves – Major Equipment Changes

• Relocation of a major manufacturing facility– No changes in SOPs and core personnel

– Major equipment changes

• Submission category depends on equipment change

– Contact your CSO

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Facility Moves – No Changes

• Relocation of a major facility where product manufacturing is performed

– No change in SOPs, core center personnel and major equipment

• Submit Form FDA 2830 or update registration on the FDA website

– Within 5 days of the change (607.26)

• Report in your Annual Report

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Product Testing Laboratory Relocation

• Evaluated on a case-by-case basis

• Contact your CSO

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Legal Name Changes

• Change in applicant’s legal name

– Issue a new license number

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What to Submit for Legal Name Changes

• Cover letter, which includes:

– New legal name exactly as it will appear on the label

– Statement that you will continue to prepare products in same manner as prepared under the old U.S. License number using the same:

• Equipment

• Manufacturing procedures and methods

• Core personnel

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What to Submit for Legal Name Changes (cont.)

• Labels– Submit final printed label showing the firm’s new

legal name and new U.S. License Number once it is issued

– Submit as a CBE labeling supplement

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Guidance Documents• “For the Submission of Chemistry, Manufacturing

and Controls and Establishment Description Information for Human Blood and Blood Components Intended for Transfusion or for Further Manufacture and for the Completion of Form FDA 356h” (May 1999)

• “Changes to an Approved Application: Biological Products: Human Blood and Blood Components Intended for Transfusion or for Further Manufacture” (July 2001)

• Link: FDA website A to Z Subject Index - G Page­ Click Guidance Documents – Biologics­ http://www.fda.gov/SiteIndex/ucm148505.htm