Letter - Potential Review Issues - Hiberix
Department of Health & Human Services
Public Health Service
Food and Drug Administration
Rockville, MD 20852-1448
Our STN: BL 125347/0
GlaxoSmithKline Biologicals, S.A.
Attention: Elisa Harkins
North American Regulatory Affairs - Vaccines
2301 Renaissance Blvd.
P.O. Box 61540
King of Prussia, PA 19406
Dear Ms. Harkins:
Please refer to your biologics license application (BLA), submitted under section 351 of the Public Health Service Act, and to our filing letter dated April 14, 2009. While conducting our filing review we identified the following potential review issues:
The following pertains to product manufacture of your product:
- Container closure integrity PQ/validation data for the Container Closure System was not included in section 3.2.P.7 of your BLA submission. Please provide this information and include summary data of any extractables/leachables studies.
We acknowledge that we are deferring discussion of a potential larger scale postmarketing safety study pending the results of your postmarketing confirmatory study (Hib-097). However, we have the following comments which pertain to post-marketing surveillance:
- Please specify your enhanced pharmacovigilance procedures for evaluating the three identified adverse events (deaths, leukocytoclastic vasculitis, and type III hypersensitivity reactions), as well as potential unanticipated safety signals.
- We recommend that the following post-marketing adverse events should also be reported in an expedited fashion in addition to 21 CFR 600.80 requirements. This expanded adverse experience reporting should be provided as 15-day reports to the Vaccine Adverse Event Reporting System for one year following product licensure as follows:
All serious adverse events whether expected/labeled or unexpected/unlabeled, including but not limited to vaccine failure, seizures, shock, respiratory distress or difficulty breathing, angioedema, inspiratory stridor, and bilateral wheezing.
- Please acknowledge that post-licensure distribution reports will be submitted to CBER on a monthly basis for one year following licensure and then every six months in accordance with 21 CFR 600.81.
Additional comments regarding the revised concept protocol for Study-097 submitted on March 31, 2009, will be sent to you separately.
We are providing the above comments to give you preliminary notice of potential review issues. Our filing review is only a preliminary evaluation of the application and is not indicative of deficiencies that may be identified during our complete review. Issues may be added, deleted, expanded upon, or modified as we review the application. If you respond to these issues during this review cycle, we may not consider your response before we take an action on your application. Following a review of the application, we shall advise you in writing of any action we have taken and request additional information if needed.
If you have any questions, please contact the Regulatory Project Manager, Jason Humbert, at (301) 827-3070.
Wellington Sun, M.D.
Division of Vaccines and Related Products Applications
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research