CBER REGULATORY REVIEW          04 March, 2014
To  Administrative File: STN 125512/0 
From  Dr. Hyesuk Kong
      Laboratory of Microbiology, In-vivo Testing & Standards (LMIVTS) 
Through  Dr. James L. Kenney, Chief 
        LMIVTS/ Division of Biological Standards and Quality Control (DBSQC) 
         Dr. William M. McCormick, Director
         DBSQC/OCBQ/CBER/FDA 
Subject  BLA, Review of Sterility and Bacterial Endotoxin Test Qualifications for Antihemophilic Factor (Recombinant), Porcine Sequence (OBI-1) 

Recommendation 
Based on the scope of this review, I recommend approval of this Biological License Application (BLA).
Conclusion
After a thorough review of this BLA, this reviewer finds Baxter Healthcare Corporations (Baxter) sterility, -------------------(b)(4)--------------------------------------- bacterial endotoxin test (BET) methods were qualified in accordance with ------(b)(4)--------------------, respectively, by demonstrating the Antihemophilic Factor (Recombinant), Porcine Sequence (OBI-1) matrix is suitable for these intended test methods.
Background
Under the rolling review agreement with CBER in accordance with to 21 CFR 601.2, Baxter submitted the first of three portions of this BLA on 10 October, 2013 and Part 2 of 3 of the rolling review submission (amendment 125512/0.1) on 8 November 2013 requesting priority review for their OBI-1 product. OBI-1 is indicated for the treatment of bleeding episodes in subjects with congenital hemophilia A and acquired hemophilia with inhibitors to human factor VIII. It is a purified, recombinant porcine factor VIII glycoprotein produced in baby hamster kidney cells and is supplied as a white lyophilized powder in single-dose vials, with polysorbate 80, sodium chloride, calcium chloride, sucrose, tris, and sodium citrate as excipients. Once reconstituted with 1.0 mL of sterile water for injection, each vial contains 500 Units of factor VIII activity. Unopened vials must be stored at 2 to 8C. Once reconstituted, the vial of OBI-1 should be used within 3 hours or discarded. 
The OBI-1 ----(b)(4)---------------- is formulated at Baxters ---(b)(4)------ facility and is shipped to -------(b)(4)----------------- located ----(b)(4)---------, where it is (b)(4), sterile filtered and aseptically filled into vials ----(b)(4)----- prior to lyophilization. No additional components are added to the DS prior to filling and lyophilization. 
The DBSQC reviews BLA and their Supplements to ensure analytical methods are appropriate, properly validated and the product matrix is suitable for the intended test method. DBSQC also reviews release specifications for microbial and endotoxin testing to ensure they reflect process capability and meet regulatory compliance. These review activities support DBSQCs lot-release mission, which is the confirmatory testing of submitted product samples and review of manufacturers lot-release protocols to ensure biological products are released according to licensed test methods and product specifications. Therefore, this review will focus on: 1) the sterility and -(b)(4)-- BET method qualifications performed on Baxter OBI-1 drug product (DP); 2) the --------------(b)(4)----------------------------------; and 3) BET release specification.
Review
Sterility
-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 
---------------(b)(4)----------------------- 
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Endotoxin
--------------------(b)(4)--------------------
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- .
----------------------(b)(4)------------------------
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
---------------------------------------------------------(b)(4)----------------------------------------------------------------------------------------------------------------------. 
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Summary
After a thorough review of the information submitted in this BLA, this reviewer finds Baxters OBI-1 product matrix is suitable for testing using their sterility and bacterial endotoxin testing methods; these tests were qualified and performed in accordance with ----(b)(4)------------------, respectively. Therefore, this reviewer finds these methods acceptable for their intended purpose and recommends their approval.
