1. CBER 1 Establishment Submissions Rosia E. Nesbitt, BS, SBB(ASCP), CQA(ASQ) Consumer Safety Officer CBER, OBRR, DBA September 15, 2009

2. CBER 2 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

3. CBER 3 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

4. CBER 4 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)

5. CBER 5 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

6. CBER 6 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

7. CBER 7 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

8. CBER 8 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

9. CBER 9 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”

10. CBER 10 What to Submit for Mergers (cont.) List of approved SOPs Updated Form FDA 2830 or update registration on the FDA website

11. CBER 11 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

12. CBER 12 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

13. CBER 13 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

14. CBER 14 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

15. CBER 15 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

16. CBER 16 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

17. CBER 17 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.)

18. CBER 18 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

19. CBER 19 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

20. CBER 20 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]

21. CBER 21 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]

22. CBER 22 Acquisitions by an Unlicensed Buyer General 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

23. CBER 23 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

24. CBER 24 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

25. CBER 25 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

26. CBER 26 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

27. CBER 27 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

28. CBER 28 Manufacturer Reducing Operations What 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

29. CBER 29 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

30. CBER 30 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

31. CBER 31 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)

32. CBER 32 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)

33. CBER 33 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

34. CBER 34 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

35. CBER 35 Product Testing Laboratory Relocation Evaluated on a case-by-case basis Contact your CSO

36. CBER 36 Legal Name Changes Change in applicant’s legal name – Issue a new license number

37. CBER 37 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

38. CBER 38 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

39. CBER 39 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