From:   Maruna, Thomas
Sent:   Tuesday, September 30, 2014 2:17 PM
To:   Daizadeh, Iraj (iraj_daizadeh@baxter.com)
Cc:   Ananyeva, Natalya; Valencia, Iliana; Lee, Timothy
Subject:   Information Requested: BLA 125512/0 - Please Respond By October 7, 2014
Importance: High
Baxter Healthcare Corporation
Attention: Iraj Daizadeh, PhD
September 30, 2014
Sent by email
Dear Dr. Daizadeh:
We are reviewing your November 25, 2013 biologics license application (BLA) indicated for the treatment and prevention of bleeding episodes in patients with acquired inhibitory antibodies to human factor VIII (i.e., acquired hemophilia patients) for the following:
STN                 Name of Biological Products 
BL 125512/0   Antihemophilic Factor (Recombinant), Porcine Sequence
Please address the following:
1. We reviewed your August 24, 2014 response to Question 4 discussed at the Late-Cycle Meeting and found your assessment of the suitability of the Upper Release Limit (URL) established for the parameter ----------(b)(4)------------------------------- inconclusive. Regression analysis of the stability data for the three Lots -------------(b)(4)--------------------- yielded the (b)(4) level of -----(b)(4)--------------, and the analysis of combined worst-case conditions (with URL of (b)(4)- from the tolerance interval analysis of the release data and the worst-case slope from the regression analysis of the stability data) yielded the (b)(4)-- level of ----(b)(4)-----------. Please note that both values are outside of the proposed Upper Specification Limit (USL) of (b)(4) and contradict your conclusion of the suitability of the URL (b)(4). Please also note that the USL in Figure 7 is set at (b)(4) and not at(b)(4). Please clarify your rationale for your conclusion that the URL of (b)(4) will assure that (b)(4) will remain within the Specification of (b)(4) at the end of shelf-life, or resolve the discrepancy.
2. Please re-instate the parameter OSCA/CS ratio in the Drug Product Specification “For Information Only”. Please also confirm that actual test results for the parameters FVIII Activity by the Chromogenic assay and the OSCA/CS ratio will be stated in the Certificate of Analysis.
The review of this submission is on-going and issues may be added, expanded upon, or modified as we continue to review this submission.
Please submit your responses as an amendment to this file by October 7, 2014 referencing the date of this request.
The action due date for these files is October 25, 2014.
If you have any questions, please contact me at (240) 402-8454 or thomas.maruna@fda.hhs.gov.
Very Respectfully,
Thomas J. Maruna, MSc, MLS(ASCP)CM
Lieutenant, U.S. Public Health Service
Senior Regulatory Management Officer
Food and Drug Administration
Center for Biologics Evaluation and Research
Office of Blood Research and Review
10903 New Hampshire Ave.
Silver Spring, MD 20993
thomas.maruna@fda.hhs.gov
O: (240) 402-8454
www.usphs.gov
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