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Our Reference:    Ref. #125402/0.30
CRMTS #9019

TODAY’S DATE: July 11, 2013    

PAGES: 3 

TO: Angela Blackshere 
Baxter Healthcare Corporation  
Email address: Angela_Blackshere@baxter.com

FROM: Alpa Shah
Regulatory Project Manager 
Division of Blood Applications
Office of Blood Research and Review
Phone number: (301) 827-6122
Fax number: (301) 827-2857

SUBJECT: Summary of FDA Internal Meeting 

PRODUCT: Immune Globulin Infusion (Human), 10% with recombinant Human 
Hyaluronidase biologic license application IGIV (rHuPH20)

FDA is canceling the July 25, 2013, 9 a.m. – 10:30 a.m. EDT, Face-To-Face 
Meeting with you regarding this product.  FDA has answered all questions 
regarding the deficiencies of the BLA contained in the CR letter, dated July 27, 
2012, and only a few items remain to be submitted for review.  These responses 
are the official FDA responses to your questions.

If you have any questions or require further discussion regarding these 
remaining issues, please contact us.

Questions from the Sponsor:

8.1 Pharmacology/Toxicology

Baxter Question 1:
The CR letter noted that the BLA did not contain sufficient preclinical 
information in relevant species to assess the possible toxicities of anti-PH20 
antibodies.

Does the Agency agree that the identified deficiencies have been addressed by 
the additional information/studies described in the briefing book submitted on 
27 March 2013 (STN BL 125402/Amendment 026), and submitted in Baxter’s 8 May 
(STN BL 125402/Amendment 027) and 14 June 2013 (STN BL125402 / Amendment 029) 
responses to FDA’s 16 and 24 April 2013 IRs, along with the final reports of the 
male fertility and female fertility/embryo-fetal development studies (12208 and 
12195, respectively) submitted in this STN BL 125402 Amendment 030?

FDA Response to Question 1:
No.

Baxter Question 2:
If the Agency does not agree, please comment on what deficiencies have not been 
addressed?

FDA Response to Question 2:
Toxicological data on life-long exposure to anti-PH20 antibodies is missing. 
 The re-submission should address this concern via an appropriate animal study, 
adequate postmarketing commitment, label warning, or other appropriate 
strategies.

Additional Comments:

In your re-submission of the BLA, please provide the following:
  The results from qPCR analysis of PH20 gene expression during development in 
  rabbits (similar to the previous Study 12196 in mice), to provide additional 
  support for the developmental and reproductive toxicology studies you have 
  performed;
  A clinical safety update for patients in the EU who have received HyQvia, and 
  an update on the number of patients enrolled in the EU pregnancy registry;
  A timeline for completion of the rabbit developmental toxicity study (Halozyme 
  Protocol 12195) addressing effects of anti-PH20 antibodies on embryo-fetal 
  development and postnatal evaluation.

8.2 Regulatory

Baxter Question 3:
Does the Agency agree that the data and information submitted address the items 
in the CR letter and therefore, a path to licensure can be defined within the 
current timeframe of the BLA, by 27 July 2013?

FDA Response to Question 3:
We agree that the data and information already submitted, plus an appropriate 
reply to concerns regarding life-long exposure to anti-PH20 antibodies (see 
response to Question 2), constitutes a full reply to concerns raised in the July 
27, 2012 CR letter.  We also agree to a 4-month extension of the BLA timeframe 
so you can address the Additional Comments provided in this letter.

FDA Additional Comment
  Please submit a clinical safety update report on HyQvia usage in the Europe 
  Union.

END
 

    