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FOOD AND DRUG ADMINISTRATION
CENTER FOR BIOLOGICS EVALUATION AND RESEARCH
MEMORANDUM

Date: 12.11.2013

From: Jennifer L. Reed, Ph.D.; CBER/OBRR/DH/LPD
HFM-345; 301-496-0625

To: File for BLA 125402

Reference: IND 13840; STN BL 125105 (Immune Globulin Intravenous (Human), 10% 
Solution; Gammagard Liquid); NDA 21-859 (hyaluronidase human injection, Hylenex)

Through: Dorothy Scott, M.D.; CBER/OBRR/DH/LPD; HFM-345; 301-827-3016

Cc: Cherie Ward-Peralta; CBER/OBRR/DBA; HFM-380; 301-827-9170

Subject: Acknowledgement of CR Reply, Assignment as Class 2
Product: Immune Globulin Infusion (Human), 10% with Recombinant Human 
Hyaluronidase: HYQVIA
Submission Date: November 26, 2013
Manufacturer: Baxter Healthcare Corporation

Recommendation:

The current electronic submission is a reply to the Agency’s complete response 
letter.
1) The Sponsor has proposed as a post-marketing commitment a preclinical study 
titled “A GLP Juvenile Toxicity Study with an Extension Arm to Assess Chronic 
Exposure of Anti-rHuPH20 Antibodies in the Mouse”. The Sponsor proposes that the 
extended duration of this study will provide adequate information on potential 
toxicities associated with life-long exposure with anti-PH20 antibodies. The 
Sponsor proposes a type C meeting after licensure to work out the details of 
study design. 
2) The Sponsor also proposes new risk mitigation measures as post-marketing 
commitments. The measures include long-term surveillance of HyQvia recipients, 
to acquire information on anti-PH20 antibody levels and evaluate the incidence 
and severity of adverse events. A pregnancy exposure registry will also be 
established to actively collect safety information related to fetal development 
and infant health through the first two years of life. 
3) A new package insert is provided.
4) A final toxicology report, “Effects of Anti-rHuPH20 Antibodies on Female 
Fertility and Embryo-Fetal Development with Postnatal Assessments in the 
--------------(b)(4)-------- Rabbit”, is not provided but is expected to be 
available in the next two weeks.

This resubmission contains proposals to address important unresolved potential 
safety concerns. The submission contents are complex as they include proposals 
for new animal toxicology studies as well as initiation of long-term followup of 
patients, and a pregnancy registry. In particular, the post-marketing safety 
surveillance proposal may need input from an internal and/or advisory 
committees. Also, it is preferable to work out the details of the outstanding 
toxicology study prior to licensure, not after. For these reasons, and in 
accordance with CBER SOPP 8405.1, the Sponsor’s reply to CR should be a Class 2 
resubmission, to allow adequate CBER time to evaluate and negotiate important 
PMC proposals.
 

    
 