Product Approval Information
Public Health Service
Food and Drug Administration
Center for Biologics Evaluation and Research
Division of Manufacturing and Product Quality
MEMORANDUM: Recommendation to Waive Pre-Approval Inspection
| Date: | July 29, 2008 |
| From: | Marion Michaelis, Reviewer, OCBQ/DMPQ/MRB II, HFM-676 |
| To: | Administrative Bundled File, Biotest AG (LIC #1702): |
Products for use on the Tango Automated Blood Group Analyzer |
| (STN) | Biological Products | Cell Line(s) | Strip Proprietary Name |
|---|---|---|---|
|
BL 125097/10 |
Blood Grouping Reagent, Anti-D (Monoclonal)(IgM) (Formulated for Automated Testing) |
BS226 |
Component of
Erytype S Rh+K |
| Blood Grouping Reagent, Anti-D (Monoclonal)(IgM) (Formulated for Automated Testing) |
BS232 |
Component of Erytype S Rh+K |
|
| BL 125206/0 | Blood Grouping Reagent, Anti-C (Monoclonal) (Formulated for Automated Testing) |
MS24/P3x25513G8
|
Component of Erytype S Rh+K |
| BL 125202/0 | Blood Grouping Reagent, Anti-E (Monoclonal) (Formulated for Automated Testing) |
MS260/MS12
|
Component of Erytype S Rh+K |
| BL 125205/0 | Blood Grouping Reagent, Anti-c (Monoclonal) (Formulated for Automated Testing) |
MS33
|
Component of Erytype S Rh+K |
| BL 125203/0 | Blood Grouping Reagent, Anti-e (Monoclonal) (Formulated for Automated Testing) |
MS16/MS21/ MS63
|
Component of Erytype S Rh+K |
| BL 125204/0 | Blood Grouping Reagent, Anti-K (Monoclonal) (Formulated for Automated Testing) |
MS56
|
Component of Erytype S Rh+K |
NOTE- Erytype S are strip wells (eight wells per strip) containing: Anti-D, Anti-D, Anti-C, Anti-c, Anti-E, Anti-e and Anti-K+ Neg Cont
BL 125208/0 |
Reagent Red Blood Cells For Use in Automated Systems | Cell Line(s) |
|---|---|---|
| Erytypecell A 1 and B | N/A |
|
| Biotestcell Pool; Biotestcell 1, 2; Biotestcell 3 | N/A |
|
Biotestcell I8; Biotestcell I11 |
N/A
|
|
| BL 125218/0 | Blood Grouping Reagent Anti-D (Monoclonal) (IgG Blend) | BS221/H4111B7 |
Seraclone- Liquid BGR for manual tube testing :
| (STN) | Biological Products | Cell Line(s) |
|---|---|---|
| BL 125222/0 | Blood Grouping Reagent, Anti-D (Monoclonal) (IgM) | BS226 |
| BL 125223/0 | Blood Grouping Reagent, Anti-D (Monoclonal Blend) | BS232/BS221/H4111B7 |
| BL 125226/0 | Blood Grouping Reagent, Anti-C (Monoclonal) | MS24 |
| BL 125227/0 | Blood Grouping Reagent, Anti-c (Monoclonal) | MS33 |
| BL 125228/0 | Blood Grouping Reagent, Anti-E (Monoclonal) | MS12/MS260 |
| BL 125229/0 | Blood Grouping Reagent, Anti-e (Monoclonal) |
MS16/MS21/MS63 |
| BL 125212/0 | Blood Grouping Reagent, Anti-Fy a (Monoclonal) | GD-FYA-02 |
| BL 125214/0 | Blood Grouping Reagent, Anti-s (Monoclonal) |
P3YAN3 |
| BL 125216/0 | Blood Grouping Reagent, Anti-S (Monoclonal) |
MS94 |
| BL 125217/0 | Blood Grouping Reagent, Anti-Jk b (Monoclonal) | MS8 |
| BL 125231/0 | Blood Grouping Reagent, Anti-Jk a (Monoclonal) | MS15 |
| BL 125219/0 | Blood Grouping Reagent, Anti-A (Murine Monoclonal) | A003 |
| BL 125220/0 | Blood Grouping Reagent, Anti-B (Murine Monoclonal) | B005 |
| BL 125221/0 | Blood Grouping Reagent, Anti-A,B (Murine Monoclonal) | BS63 and BS85 |
| BL 125224/0 | Blood Grouping Reagent, Anti-M (Murine Monoclonal) | BS57 |
| BL 125225/0 | Blood Grouping Reagent, Anti-N (Murine Monoclonal) | BS41 |
| BL 125230/0 | Blood Grouping Reagent, Anti-K (Monoclonal) | MS56 |
| BL 125232/0 | Blood Grouping Reagent, Anti-k (Murine Monoclonal) | Lk1 |
| BL 125233/0 | Blood Grouping Reagent, Anti-Le a (Murine Monoclonal) | LEA2 |
| BL 125213/0 | Blood Grouping Reagent, Anti- P 1 (Murine Monoclonal) | 650 |
Other Reagents for Manual Tubes Testing
| (STN) | Anti-Human Globulin | Cell Line(s) | |
|---|---|---|---|
| BL 125242/0 | Anti-Human Globulin (Rabbit/Murine Monoclonal) | BRIC-8 |
|
| BL 125215/0 | Anti-Human Globulin | N/A |
|
| BL125098/8 | Anti-Human Globulin (Formulated for Automated Testing) | N/A |
|
| (STN) | Reagent Red Blood Cells | Cell Line(s) |
|
| BL 125207/0 | Biotestcell A 1 and B | N/A |
|
| Biotestcell A 2 | N/A |
||
| Biotestcell Pool; Biotestcell 1, 2; Biotestcell 3 | N/A |
||
| Biotestcell I8; Biotestcell I11 | N/A |
||
Applicant: Biotest AG, Dreieich, Germany location.
Products: See above bundled file listing.
Through: Chiang Syin, Ph.D., Branch Chief, OCBQ/DMPQ/MRB II, HFM-676
Concurrent Clearance Routing
| ________________________________________________________ | _____ | ________ |
| John A. Eltermann, Jr., R.Ph., M.S. | Date | CONCUR |
| Director, Division of Manufacturing and Product Quality, HFM-670 | ||
| Office of Compliance and Biologics Quality | ________ | |
| Center for Biologics Evaluation and Research | DO NOT CONCUR |
| ________________________________________________________ | _____ | ________ |
| Elizabeth Callaghan | Date | CONCUR |
| Acting Director, Division of Hematology, HFM-370 | ||
| Office of Blood Research and Review | ________ | |
| Center for Biologics Evaluation and Research | DO NOT CONCUR |
Summary
We recommend waiver of the pre-approval inspection, BLAs and BLS for Biotest AG, for manufacturing multiple new Blood Grouping Reagents, Anti-Human Globulin, and Reagent Red Blood Cells (specified above).
Brief History
Biotest AG, U.S. License 1702, Dreieich, Germany, submitted a bundle consisting of 30 new BLAs and 2 BLSs in September 2006 (see above). Biotest is currently licensed to manufacture several Erytype S Blood Grouping Reagents are for use on the TANGO Automated Blood Bank System. The purpose of this submission is to obtain approval for additional monoclonal antibodies as components of Erytype S plates, to update the CMC with information related to sublotting and testing of bulk antibodies, and to obtain approval for a complete line of liquid reagents for use in manual immunohematology tube tests.
This bundle is a companion submission to 4 BLAs for Blood Grouping Reagents (Monoclonal)(For Further Manufacturing Use)(FFMU) submitted by DIAGAST, U.S. License 1744; and 10 BLSs and 2 BLAs for Blood Grouping Reagents (Monoclonal)(For Further Manufacturing Use)(FFMU)and Anti-Human Globulin (Murine Monoclonal)(For Further Manufacturing Use)(FFMU) submitted by Millipore (Celliance) U.S. License 1721. The BLAs/BLSs were submitted by DIAGAST and Millipore in September 2006.
Description of Change:
- BLAs for manufacturing new Blood Grouping Reagents, Anti-Human Globulin, and Reagent Red Blood Cells (specified above) and associated process and manufacturing changes to previously licensed BGR’s.
Basis for the Waiver:
This waiver is based on criteria outlined in Center wide SOPP 8410 “Determining When Pre-Licensing/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.
Biotest AG, Dreieich, Germany does hold U.S. license No. 1702.
- The FDA has not inspected the facility in the last two years.
This facility ( Dreieich, Germany) in the last two years was inspected by:
- The first inspection was conducted by Team Biologics (Jacqueline Diaz Albertini) during the time period of 19-28 September 2006 and was a GMP inspection done as part of the Team Biologics work-plan for FY 2006.
- The second inspection was conducted by CBER (Susan Yu and Joanne Pryzbylik) during the week of June 28 through July 6, 2004 and was a Pre-Licensing Inspection (PLI) for the manufacture of Blood Grouping Reagents (BGR) and Anti-Human Globulin (AHG) for use on the TANGO, an automated blood bank analyzer.
- The previous inspection(s) revealed significant GMP violations in areas related to the processes in the submission (similar processes) or systemic problems, such as QC/QA oversight.
- The inspection in September 2006 was classified VAI. The GMP inspection was done as part of the Team Biologics work-plan for FY 2006.
- The inspection in June-July 2004 was classified VAI. The PLI inspection was conducted for the manufacture of Blood Grouping Reagents (BGR) and Anti-Human Globulin (AHG) for use on the TANGO, an automated blood bank analyzer.
- The inspection in September 2006 was classified VAI. The GMP inspection was done as part of the Team Biologics work-plan for FY 2006.
- 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.
All areas used for the manufacturing are licensed areas.
- The manufacturing process is sufficiently different (new production methods), specialized equipment or facilities) from that of other approved products produced by the establishment.
The production process is similar to other immunohematology reagents and systems for blood grouping, phenotyping, and antibody screening products produced at the facility.
Waiver Recommendation:
Based on the information provided in the BLA 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.
_____________________________ 07/29/08_
Marion Michaelis, HFM-676 Date
Reviewer, DMPQ