Information Request Email, February 15, 2013 - RIXUBIS
From: Thompson, Edward
Sent: Friday, February 15, 2013 8:04 AM
To: 'Kevin Smyth (email@example.com)'
Cc: Ovanesov, Mikhail V.; Omokaro, Stephanie
Subject: Information Request for BL 125446/0
Contacts: Kevin Smyth
Dear Mr. Smyth:
We are reviewing your August 28, 2012 biologics license application (BLA). We are providing the following comments and request for additional information to continue our review:
A. You have reported the development of antibodies to rFurin in 11 out of 86 subjects who received your product.
1. Please submit the risk assessment analysis addressing potential safety concerns of these findings along with the associated clinical significance.
2. Please present the results of the confirmatory assay on all subjects that were positive with the screening assay. We expect these values to be zero and will further validate the confirmatory assay.
3. Please submit in graphical format information for each individual who developed antibodies to rFurin.
4. Please provide in tabular format:
a. PK data for subjects with positive antibodies to rFurin
b. Number of bleeding episodes for each of these subjects pre and post detection of antibody
c. Percent and change from baseline of eosinophils for each of these subjects pre and post detection of antibody
d. IgE levels if available for each of these subjects pre and post detection of antibody
e. Use of anti-allergic concomitant medications (such as anti-histamines, epinephrine, steroids, etc) for each of these subjects pre and post detection of antibody
f. Data on clinical findings/other adverse events observed for each of these subjects on the day antibody was detected
g. Indicate disposition for each of these subjects (i.e. continuing the study, withdrawal, etc)
h. Site and country for each of these subjects
i. Indicate whether or not each of these subjects are still receiving BAX326
j. Results of latest antibody testing
5. Please submit to the BLA all materials regarding antibodies to rFurin that were discussed with the product reviewer during the facility inspection.
6. Please provide information on results that have been obtained in healthy individuals tested using in-house assays for rFurin including percent estimate of antibody occurrence in this population.
- Please submit all the above information on the subjects who were positive for FIX binding antibodies.
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 response to this information request as an amendment to this file by March 1, 2013 referencing the date of this request. If you anticipate you will not be able to respond by this date, please contact the Agency immediately so a new response date can be identified.
If we determine that your response to this information request constitutes a major amendment, we will notify you in writing.
The action due date for this file is tentatively June 30, 2013.
If you have any questions, please contact me at (301) 827-9167.
Regulatory Project Manager
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