From: Maruna, Thomas
Sent: Friday, February 14, 2014 1:43 PM
To: Daizadeh, Iraj (iraj_daizadeh@baxter.com)
Cc: Ananyeva, Natalya; Bobo, Qiao
Subject: Information Requested: BLA 125512 Please Respond By [Q10-12: Feb 21, 2014] [Q1-9: Feb 28, 2014] 
Importance: High
Baxter Healthcare Corporation
Attention: Iraj Daizadeh, PhD
February 14, 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         Antihemophilic Factor (Recombinant), Porcine 
We determined that the following information is necessary to continue our review:
1. Please provide data or justification for the hold times established for the Drug Substance intermediates.

2. Please provide a summary of cleaning validation performed for your product contact equipment used during the manufacturing of the Drug Substance including cleaning method, soil used, justification for the soil used, acceptance criteria, justification for the acceptance criteria used, results and conclusion.

3. Please provide a summary of shipping validations performed for shipping ----(b)(4)------------- from Baxter ------(b)(4)--------- facility, and the filled Drug Product from ---(b)(4)------ facility to Baxter ----(b)(4)----------------------- site.

4. Please provide a summary of the validation and the validation report for the lyophilizer used for manufacturing of OBI-1 final product. 

5. Please provide more detail for the positive controls used in your container closure integrity tests (-------------------(b)(4)------------------------). Please justify that your tests are capable of detecting minute leaks in your container closure system. 

6. For the -----(b)(4)-------- site, please justify the use of OBI-1 as the challenge soil for cleaning validation of multi-use product contact equipment.

7. Please provide a summary of validation or qualification performed for visual inspection, labeling and packaging process performed at the Baxter -----(b)(4)-------------- site (-----(b)(4)------------------) and the ----(b)(4)------------- site if applicable. 

8. Please provide a list of tests performed on the Drug Product before and after labeling at your Baxter ------------(b)(4)---------------- facility -----(b)(4)-----------.

9. Baxter’s request for Categorical Exclusion under 21CFR25.31(j) was not appropriate. OBI-1 is not a biologic product for transfusable human blood or blood component and plasma. Please submit a request for Categorical Exclusion with the basis as outlined in 21CFR Part 25.31(c), and provide your justifications.

10. Please provide a list of FDA licensed products that use the same diluent (Water for Injection) as the one used for OBI-1 from the same manufacturer -------------(b)(4)--------------------------------------------------------------------------- and same manufacturing location. Please provide a tabular comparison of the following: fill volume, fill equipment, manufacturing process, container closure system used, sterilization process and testing performed.

11. The Letter of Authorization from -------------------------------------(b)(4)-----------------------------------. Please clarify what ----(b)(4)--- are and how they relate to your BLA.

12. The Letter of Authorization from -------------(b)(4)-------------------------- references DMF “Sterile Water for Injection” but does not have a DMF number associated with it. Please provide a DMF number for the reference. Please clarify how the Sterile Water for Injection from ---------(b)(4)---------------------------------------- is related to your BLA. 
If the Sterile Water for Injection is used as diluent, please provide the manufacturing location and the FEI. Please provide a list of FDA licensed products that use the same diluent (Water for Injection) as the one used for OBI-1 from the same manufacturer (------(b)(4)----------------------------) and same manufacturing location. Please provide a tabular comparison of the following: fill volume, fill equipment, manufacturing process, container closure system used, sterilization process and testing performed.
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 to questions 10 - 12 as an amendment to this file by February 21, 2014 and questions 1 – 9, also as an amendment to this file, by February 28, 2014, referencing the date of this request.
If it is not feasible for Baxter to provide all responses by February 28th, Baxter may provide partial response and indicate the new date for the remainder of responses.
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 
"THIS MESSAGE IS INTENDED ONLY FOR THE USE OF THE PARTY TO WHOM IT IS ADDRESSED AND MAY CONTAIN INFORMATION THAT IS PRIVILEGED, CONFIDENTIAL, AND PROTECTED FROM DISCLOSURE UNDER LAW. If you are not the addressee, or a person authorized to deliver the document to the addressee, you are hereby notified that any review, disclosure, dissemination, copying, or other action based on the content of this communication is not authorized. If you have received this document in error, please immediately notify the sender immediately by e-mail or phone." 

