From: Maruna, Thomas
Sent: Wednesday, March 19, 2014 12:04 PM
To: Daizadeh, Iraj (iraj_daizadeh@baxter.com)
Cc: Bobo, Qiao; Ananyeva, Natalya
Subject: Information Requested: BLA 125512/0 To be Discussed During Telecon (Mar 20, 2014) 
Importance: High
Baxter Healthcare Corporation
Attention: Iraj Daizadeh, PhD
March 19, 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 Porcine, B-Domain Truncated Recombinant 
We have determined that the following information is necessary to continue our review: 
1. Please provide a description of your freeze dryer including manufacturer, model, number of shelves, and trays per shelf, vial capacity, and dimensions or chamber volume. Please describe the minimum and maximum capacity and the typical loading pattern for commercial manufacturing of OBI-1.

2. In your (b)(4) Freeze Dryer Requalification Report U9BF-RR4(1)-0350, please clarify how the “Freezing Segments” on pages 9 and 11 Section 5.3.1, correspond to the segments in the table on page 7 section 5.3.1 in terms of temperature and duration. Please specify whether the requalification cycle is the same as the commercial production cycle and correlate the above “segment” information to the conformance lots data provided in the original BLA Section 3.2.P.3.5 pages 9-11 in terms of temperature and duration.

3. Please justify the temperature and duration used for freezing, primary drying and secondary drying. Providing information such as the glass transition temperature, collapse temperature, and/or eutectic temperature may be helpful. 

4. Please provide more product data using commercial lyophilization cycle. Please ensure you describe your sampling method (e.g. extended sampling, sampling pattern, which shelves sampled and sample locations, number of samples taken at each location), batch size of each run, and testing results (e.g. residual moisture, potency, reconstitution time). 

5. Please confirm that the lyophilization cycle is fixed. Please provide detailed information on any changes made for any of the conformance lot runs.

6. For conformance lots, please provide the number of vials went into the freeze dryer and number of vials released for each lot. Please provide visual inspection acceptance criteria and results for these lots
These items will be discussed during the teleconference scheduled for March 20, 2014 from 11:30 a.m. to 12:30 p.m. EST. Please ensure your subject matter expert from the Ipsen facility is present. 
The review of this submission is on-going and issues may be added, expanded upon, or modified as we continue to review this submission. 
The timeline for the submission of your response will be discussed during our March 20th teleconference.
The action due date for these files is July 26, 2014.
If you have any questions, please contact me at (301) 827-6120.
Very Respectfully,
Thomas J. Maruna, MSc, MLS(ASCP)CM
Lieutenant, U.S. Public Health Service
Senior Regulatory Management Officer
Food and Drug Administration
CBER/OBRR/DBA/RPMB
1401 Rockville Pike
RM 562N, HFM-380 
Rockville, MD 20852
thomas.maruna@fda.hhs.gov
O: (301) 827-6120
BB: (240) 397-3419
www.usphs.gov 
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