MEMORANDUM Recommendation to Waive Pre-Approval Inspection
Rebecca Olin, OCBQ/DMPQ/MRB II, HFM-676, Reviewer Laura Wood, OBRR/DH/LPD, HFM-345, Committee Chair
|To:||STN File – STN BL 125317/0|
Recommendation to waive the Biologics License Application (BLA) pre-approval inspection for the manufacture of Human Fibrinogen Concentrate, Pasteurized
|Sponsor:||CSL Behring GmbH U.S. License # 1765|
|Product:||Human Fibrinogen Concentrate, Pasteurized|
Chiang Syin, PhD, HFM-676
Concurrent Clearance Routing
John A. Eltermann, Jr. , R.Ph, M.S. Date CONCUR Director, Division of Manufacturing and Product Quality, HFM-676 Office of Compliance and Biologics Quality ________ Center for Biologics Evaluation and Research DO NOT CONCUR
Basil Golding, MD Date CONCUR Director, Division of Hematology, HFM-345 Office of Blood Research and Review ________ Center for Biologics Evaluation and Research DO NOT CONCUR
Summary We recommend waiver of the pre-approval inspection for CSL Behring GmbH BLA approval supplement to include the manufacture of Human Fibrinogen Concentrate, Pasteurized in the treatment of congenital fibrinogen deficiency.
Brief History CSL Behring GmbH (hereinafter referred to as CSL) has submitted a BLA for the manufacture of Human Fibrinogen Concentrate, Pasteurized in the treatment of congenital fibrinogen deficiency.
In 2004, ZLB Behring, then known as Aventis Behring, was acquired by CSL Limited, an Australian firm specializing in the development, manufacture and marketing of biologically based health care products. In April 2007 ZLB Behring changed its name to CSL Behring and the license number was changed from 1708 to 1765 for currently licensed products. CSL Limited includes: CSL Bioplasma, CSL Biotherapies and CSL Behring. CSL Behring is headquartered in King of Prussia, PA with manufacturing facilities in Kankakee, IL, Bern, Switzerland and Marburg, Germany.
US Licensed products manufactured at CSL Behring GmbH, Marburg include Antihemophilic Factor (Human), US License 1765 (STN BL103960) and Immune Globulin Subcutaneous, Human, US License 1765 (STN BL125115).
CSL Behring GmbH also provides the following contract manufacturing services for products sold on the US market:
The current submission covers the manufacture of sterile bulk drug substance, aseptic filling and lyophilization of finish product at the Marburg facility.
Basis for the Waiver: This waiver is based on criteria outlined in Centerwide SOPP 8410 “Determining When PreLicensing/Pre-Approval Inspections are Necessary.” As stated in that SOPP, it is CBER’s policy that a pre-license or pre-approval inspection will generally be necessary for an application if any of the following criteria in bold are met:
- The facility does not hold an active US license.
- The FDA has not inspected the facility in the last two years.
CSL Behring GmbH holds US License #1765 for Antihemophilic Factor (STN BL103960) and Immune Globulin Subcutaneous (Human)(STN BL125115).
This facility was inspected by Team Biologics in a routine biennial GMP inspection dated March 27 to April 3, 2008. The inspection covered the manufacture of Humate P ® .
A Pre-approval Inspection was conducted May 26, to June 2, 2008 for the manufacture of ------------------(b)(4)------------------.
- The previous inspections revealed significant GMP violations in areas related to the processes in the submission (similar processes) or systemic problems, such as QC/QA oversight.
The last biennial inspection (March/April 2008) was classified VAI.
The pre-approval inspection resulted in the issuance of a CR letter primarily due to product related issues. FDA-483 observations cited during the May/June pre-approval inspection pertinent to this BLA (125317/0) have been resolved.
- The establishment is performing significant manufacturing step(s) in new (unlicensed) areas using different equipment (representing a process change). This would include areas that are currently dedicated areas that have not been approved as multi-product facilities/buildings/areas.
Manufacturing facilities for Human Fibrinogen are conducted in Buildings -------(b)(4)-------------------------, all currently used for US Licensed product. Major equipment is shared between HFCP and ------------(b)(4)---------------.
- The manufacturing process is sufficiently different (new production methods), specialized equipment or facilities) from that of other approved products produced by the establishment.
The manufacture of Human Fibrinogen shares manufacturing similarities with currently licensed ---(b)(4)---.
Waiver Recommendation: Based on the information provided in the BLS and related correspondence supporting the overall compliance status of the license holder, the review committee recommends waiving the pre-approval inspection for the facility changes associated with these supplements.
Rebecca Olin , CMC Reviewer, HFM-676 ________________________DATE_______
Laura Wood , Committee Chair, HFM-345________________________DATE_______