From: Maruna, Thomas
Sent: Thursday, August 21, 2014 10:34 AM
To: 'Lemieux, Linda'; Daizadeh, Iraj (iraj_daizadeh@baxter.com)
Subject: Information Request. STN BL 125512. Please respond by August 25, 2014 - Teleconference Requested (August 22, 2014)
Importance: High
Baxter Healthcare Corporation
Attention: Iraj Daizadeh, PhD
August 21, 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 Sequence
We determined that the following information is necessary to continue our review: You have given us -b(4)---- as a qualified Reference Standard for Potency to be used as standard for testing by CBER. In the June 18, 2014 e-mail (below), you provided your results from the Chromogenic assay as corrected assay values. However, these values, although they match the data in Batch Analysis (3.2.P.5.4), are significantly different from those you cited in your submission under Justification of Specification(s) (3.2.P.5.6) where you indicated that the recalculated results should be used when --(b)(4)--- is used as the Reference Standard. In Justification of Specification, the following Potency values by the Chromogenic assay are stated:
Lot # --(b)(4)--- (U/vial)
Lot # --(b)(4)---
Lot # --(b)(4)---
These results differ from your results in the June 18th e-mail by ~14%. Please clarify which data set we should use for comparison. This also brings to question if the values you provided in the June 18th e-mail for lots (b)(4)- and (b)(4)- are correct assay values. Please clarify what reference standard you used to assay lots (b)(4)- and (b)(4)-: --(b)(4)- or a different standard. If you used a different standard, please provide the assay values for these two lots re- calculated for --(b)(4)-.
In summary, please provide all Potency data by the Chromogenic assay for the five lots (release and stability data where available) with the values adjusted to the use of commercial Reference Standard for Potency --(b)(4)-, to allow comparison with the results of in-support testing by CBER/DBSQC.
A related question is why your results are 13.5% lower when --(b)(4)- standard is used, given that you have qualified each of your standard lots against the International Standard and assign values to your standard based on your qualification data. Please provide your explanation of sensitivity of the Chromogenic assay to the reference standard that is used, and comment whether the assay is sensitive to chromogenic reagent kit from your experience. 
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 August 25, 2014 referencing the date of this request.
CBER is requesting a teleconference to clarify this matter; the proposed date/time is Friday, August 22, 2014, 11:30 a.m. to 12 p.m. EST.
The action due date for these files is October 25, 2014.
If you have any questions, please contact me.
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 
"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." 
From: Lemieux, Linda [mailto:linda_lemieux@baxter.com] 
Sent: Wednesday, June 18, 2014 12:50 PM 
To: Kumar, Vasantha; Daizadeh, Iraj; Maruna, Thomas 
Subject: RE: Information Request. STN BL 125512. Please respond by June 19 via email. 
I am responding to the email request (dated June 10) on behalf of Dr. Daizadeh.
In reviewing the FDA provided chart in the email, the One Stage Coagulation Assay (OSCA) values have been confirmed, but the chromogenic assay (CA) values are not the values reported in the OBI-1 BLA SN 125512. Therefore, we have provided the corrected chromogenic assay values in the tables below.
The following three lots of OBI-1 Final Drug Product (FDP lots -------(b)(4)---------- are part of the OBI-1 stability program, the potency results through 24 months are provided in Tables 1 – 3. The results are reported as U/vial, which corresponds to U/mL, if reconstituted in the recommended 1 mL WFI.
-----b(4)-------------------------
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)----
--b(4)----
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
One page determined to be not releasable: b(4)
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)----
--b(4)---- 
--b(4)---- 
--b(4)---- 
------------------------b(4)---------------------------------------------------------- -------------------------------------:
--b(4)----------------------------------
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)------------------------------------
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)---- 
--b(4)----
--b(4)---- 
Please let me know if you have any additional questions. Thank you.
Best Regards,
Linda
Linda Lemieux
Associate Director, CMC Regulatory
Baxter Healthcare Corporation
----------
--------------
----(b)(4)-----
-----------------
From: Kumar, Vasantha [mailto:Vasantha.Kumar@fda.hhs.gov] 
Sent: Tuesday, June 10, 2014 2:08 PM
To: Daizadeh, Iraj 
Cc: Maruna, Thomas 
Subject: Information Request. STN BL 125512. Please respond by June 19 via email. 
Importance: High
Dear Dr. Daizadeh,
I am writing on behalf of Thomas Maruna. 
We are currently in the process of reviewing your BLA, BL 125512, and we need the following information to proceed with the review.
I may add that this is a follow-up to April 11, 2014 request for additional samples of OBI- Drug Product for in-support testing.
1. Please submit the following information regarding the test samples provided for the FVIII chromogenic assay in-support testing by FDA:
The manufacture date and the Potency values of the following OBI-1 samples at release as measured in the FVIII chromogenic assay:
Lot ---(b)(4)------
Lot ---(b)(4)------
The following information on Potency values at release had already been provided by Baxter as part of your application:
Reagent
Potency (U/vial) (OSCA)
Potency (U) (FVIII chromogenic assay)
---(b)(4)--
--b(4)---- 
--b(4)---- 
----(b)(4)------
--b(4)---- 
--b(4)---- 
----(b)(4)------
--b(4)---- 
--b(4)---- 
----(b)(4)------
--b(4)---- 
----(b)(4)------
--b(4)---- 
In addition, please provide the most current Potency values obtained by the chromogenic method and indicate respective dates and time points when the testing was performed for all five lots of OBI-1 Antihemophilic Factor (Recombinant), Porcine Sequence.
Please submit your responses via e-mail by June 19, 2014.
Thanks
Vasantha
Vasantha Kumar, Ph.D.
U.S.Food & Drug Administration
CBER/OBRR/RPMB
10903 New Hampshire Ave.
White Oak Building 71, Rm 4206
Silver Spring, MD 20993-0002
Phone: (240) 402-8413
Fax: (301) 595-1128
E-Mail: vasantha.kumar@fda.hhs.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 notify the sender immediately by e-mail or phone." 
The information transmitted is intended only for the person(s) or entity to which it is addressed and may contain confidential and/or legally privileged material. Delivery of this message to any person other than the intended recipient(s) is not intended in any way to waive privilege or confidentiality. Any review, retransmission, dissemination or other use of, or taking of any action in reliance upon, this information by entities other than the intended recipient is prohibited. If you receive this in error, please contact the sender and delete the material from any computer.
For Translation: http://www.baxter.com/email_disclaimer 
