Our STN: BL 125254/181
Attention: Paul R. Hartmann, R.Ph.
1020 First Avenue
P.O. Box 60446
King of Prussia, PA 17406-0446
Dear Mr. Hartmann:
We have approved your request to supplement your biologics license application for Influenza Vaccine, AFLURIA®, to include the 2010-2011 United States formulation.
Please submit all final printed labeling at the time of use and include implementation information on Form FDA 356h. Please provide content of labeling in Structured Product Labeling format. Please provide carton and container labeling in Structured Product Labeling format.
All promotional claims must be consistent with and not contrary to approved labeling. You should not make a comparative promotional claim or claim of superiority over other products unless you have substantial evidence to support that claim.
POSTMARKETING REQUIREMENTS UNDER 505(o)
Section 505(o)(3) of the Federal Food, Drug, and Cosmetic Act (FDCA) authorizes FDA to require holders of approved drug and biological product applications to conduct postmarketing studies and clinical trials for certain purposes, if FDA makes certain findings required by the statute (section 505(o)(3)(A), 21 U.S.C. 355(o)(3)(A)).
Since AFLURIA® was approved on 28 September 2007, we have become aware of postmarketing reports of increased incidence of fever and febrile seizures in pediatric subjects following administration of your 2010 Southern Hemisphere influenza vaccine. Therefore, we consider this information to be “new safety information” as defined in section 505-1(b)(3) of the FDCA.
We have determined that an analysis of spontaneous postmarketing adverse events reported under subsection 505(k)(1) of the FDCA will not be sufficient to assess a signal of a serious risk of adverse events associated with fever in pediatric subjects following administration of your influenza vaccine.
Furthermore, the new pharmacovigilance system that FDA is required to establish under section 505(k)(3) of the FDCA has not yet been established and is not sufficient to assess these serious risks.
Finally, we have determined that only a clinical trial (rather than a nonclinical or observational study) will be sufficient to assess a signal of a serious risk of adverse events associated with fever in pediatric subjects following administration of your influenza vaccine.
Therefore, based on appropriate scientific data, FDA has determined that you are required to conduct the following clinical trial:
1. A comparative trial to prospectively evaluate the risk of febrile events in pediatric subjects administered your trivalent influenza vaccine or a comparative influenza vaccine.
We acknowledge the timetable you submitted on July 27, 2010, which states that you will conduct this clinical trial according to the following schedule:
Final Protocol Submission: December 2010
Recruitment and dose 1 vaccination completed: End of April 2011
Post dose 1 interim results: End of June 2011
Post dose 2 interim results: End of July 2011
Final Report Submission: End September 2011
Please submit the protocol(s) to your IND: -(b)(4)-, with a cross-reference letter to this BLA. Submit all final reports to this BLA and prominently identify them as appropriate:
- Required Postmarketing Protocol under 505(o)
- Required Postmarketing Final Report under 505(o)
- Required Postmarketing Correspondence under 505(o)
Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of any study or clinical trial required under this section. This section also requires you to periodically report to FDA on the status of any study or clinical trial otherwise undertaken to investigate a safety issue. Section 506B of the FDCA, as well as, 21 CFR 601.70, requires you to report annually on the status of any postmarketing commitments or required studies or clinical trials.
We will consider the submission of your annual report under section 506B and 21 CFR 601.70 to satisfy the periodic reporting requirement under section 505(o)(3)(E)(ii) provided that you include the elements listed in 505(o) and 21 CFR 601.70. We remind you that to comply with 505(o), your annual report must also include a report on the status of any study or clinical trial otherwise undertaken to investigate a safety issue. Failure to submit an annual report for studies or clinical trials required under 505(o) on the date required will be considered a violation of FDCA section 505(o)(3)(E)(ii) and could result in enforcement action.
We will include the information contained in the above referenced supplement in your Biologics License Application file.
Jerry P. Weir, Ph.D.
Division of Viral Products
Office of Vaccines
Research and Review
Center for Biologics
Evaluation and Research
Attachment: Approved Final Draft Labeling