Archived Content

The content on this page is provided for reference purposes only. This content has not been altered or updated since it was archived.

Vaccines, Blood & Biologics

Waiver Memo - Bivigam


Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research
Office of Compliance and Biologics Quality
Division of Manufacturing and Product Quality
To:                   File, BL STN 125389/0
From:             Destry Sillivan, Acting Branch Chief, OCBQ/DMPQ/MRB II, HFM-676
Subject;           Recommendation to waive a pre-license inspection
Sponsor:          Biotest Pharmaceuticals Corporation (US License # 1792)
Product:          Immune Globulin Intravenous (Human) 10%
Indication:      Primary Immune Deficiency Disorders (PIDD)
Through:        Laurie Norwood, Deputy Director, OCBQ/DMPQ/ HFM-676
CC:                  Pratibha Rana, RPM, DBA/OBRR,HFM-380
CC:                 Damaris Lopez-Rosario, CSO, OCBQ/DIS/PSB, HFM-656
Concurrent Clearance Routing
_________________________ Date: _______                    _________      __________
John A. Eltermann, Jr., R.Ph., M.S.                                              CONCUR                     DO NOT CONCUR
Director, Division of Manufacturing and Product Quality, HFM-670
Office of Compliance and Biologics Quality, CBER
_________________________ Date: _______                    __________    __________
Basil Golding, MD                                                                 CONCUR                      DO NOT CONCUR
Director, Division of Hematology, HFM-345
Office of Blood Research & Review, CBER
I recommend that a pre-license inspection (PLI) be waived for Biotest’s  facility located at 5800 Park of Commerce Blvd, N.W. Boca Raton, Florida 33487, where Immune Globulin Intravenous (Human) 10% is manufactured under the BLA STN 125389/0, based on CBER SOPP 8410 “Determining When Pre-License/Pre-Approval Inspections (PLI/PAI) Are Necessary.”
Biotest submitted a BLA on November 11, 2010, STN 125389/0, for the manufacture of  Immune Globulin Intravenous (Human) 10%, a highly purified, sterile, liquid preparation of concentrated human immunoglobulin G (IgG) antibodies, using a modified Cohn/Oncley process at their facility located in Boca Raton, FL .
FDA last inspected this Biotest facility on May 9-17, 2012. This inspection was determined to be Voluntary Action Indicated per FACTS Biotest FEI 1000525461.
Basis for the Waiver
This waiver is based on criteria outlined in the Center-wide SOPP 8410 “Determining When Pre-License/Pre-Approval Inspections (PLI/PAI) Are Necessary.” As stated in the aforementioned SOPP, it is CBER’s policy that a PLI or PAI will generally be necessary for a BLA if any of the following criteria in bold are met:
  • The facility does not hold an active US license.
Biotest holds a current US license number 1792.
  • The facility has not been inspected in the last two years by the FDA.
Biotest facilities have been inspected within the last two years by FDA, as noted above. This inspection, completed by Burnell Henry of Team Biologics during the period of May 9-17, 2012, was classified as Voluntary Action Indicated.
  • 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.
Biotest, U.S. License # 1792, is manufacturing Immune Globulin Intravenous (Human) 10% in the same licensed facility using equipment shared with -----------(b)(4)--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------. Immune Globulin Intravenous (Human) 10% is manufactured in areas used exclusively for the manufacture of human Immunoglobulin products.
  • The previous inspection revealed significant GMP deficiencies in areas related to the processes in the application/supplement (similar processes) or systemic problems, such as QC/QA oversight.
The most recent surveillance inspection of Biotest in May of 2012 was classified as Voluntary Action Indicated. The cited deficiencies in these inspections were deemed not significant or no systemic impairment to be in compliance with applicable standards.
  • The manufacturing process is sufficiently different (new production methods, specialized equipment or facilities) from that of other approved products produced by the establishment.
Immune Globulin Intravenous (Human) 10% is manufactured at Biotest using a -----------------------------------------(b)(4)----------------------------------------------------------. 
Waiver Recommendation
I recommend waiving the PLI for the Biotest facility referenced in this BLA based on the information provided in the BLA, the previous inspection report and related correspondence supporting the overall compliance status of the license holder.
CDR Destry Sillivan, USPHS                       
Acting Branch Chief/CMC-Facility reviewer


Michael Kennedy, Ph..D.                  
CMC chair

Page Last Updated: 01/18/2013
Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and Players.
Language Assistance Available: Español | 繁體中文 | Tiếng Việt | 한국어 | Tagalog | Русский | العربية | Kreyòl Ayisyen | Français | Polski | Português | Italiano | Deutsch | 日本語 | فارسی | English