CSL Behring AG Letter - Hizentra, January 15, 2009

To: Paul Hartmann
CSL Behring AG
Date: January 15, 2010

This is regarding your BLA submission STN 125350/0 for Immune Globulin Subcutaneous (Human), 20% Liquid, submitted to the Agency on April 30, 2009.  FDA continues with the review of the referenced submission and requests CSL Behring AG to provide the following information.    

1. Please submit a translation of the certificate of analysis for L-proline used in study PSR 01/07 that clearly indicates the expiration date.
2. In study no. HYR 01/06, titled “Effects of Sandoglobulin, IgPro10 and IgPro20 on blood pressure in rats” in the conclusions section you state that “…lot number 43109-00001 of IgPro20 caused a similar hypotension … to Sandoglobulin. Lot 43109-00002 appeared to cause a slightly more pronounced hypotension.” However, according to table 2 (pg 14) the opposite is true.  You continue to say that such an effect “…was in the range of the model’s variance”.  Please clarify.
3. Please submit the names of the responsible personnel corresponding to the signatures shown in “Legacy Study Report Bacterial Stress Gene Assay Zen-0995” signature page (pg 2).

Please submit a response to this request as an amendment to the file by January 30, 2010.  Responses to items 2 and 3 (sent to you in a previous IR) were not located; please cross-reference if already sent.

Thank you.

Pratibha Rana