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U.S. Department of Health and Human Services

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December 14, 2012 Approval Letter- Fluarix Quadrivalent

 

Our STN: BL 125127/513
 
GlaxoSmithKline Biologicals
Attention: Judith Magner
2301 Renaissance Boulevard
P.O. Box 61540
King of Prussia, PA 19406-2772
 
Dear Ms. Magner:
 
We have approved your request to supplement your biologics license application (BLA) for Influenza Virus Vaccine to include a quadrivalent influenza virus vaccine formulation (Fluarix® Quadrivalent) for use in persons 3 years of age and older.
The review of this product was associated with the following National Clinical Trial (NCT) numbers:  NCT00714285, NCT00985790, NCT01196988 and NCT01204671.
 
Please provide your final content of labeling in Structured Product Labeling (SPL) format and include the carton and container labels. In addition, please submit three original paper copies for carton and container final printed labeling.  All final labeling should be submitted as Product Correspondence to this BLA at the time of use (prior to marketing) and include implementation information on FDA Form 356h.
 
In addition, please submit the final content of labeling (21 CFR 601.14) in SPL format via the FDA automated drug registration and listing system, (eLIST), as described at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Information on submitting SPL files using eLIST may be found in the guidance for industry titled, “SPL Standard for Content of Labeling Technical Qs and As” at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072392.pdf.
 
You may submit two draft copies of the proposed introductory advertising and promotional labeling with an FDA Form 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448.  You must submit copies of your final advertisement and promotional labeling at the time of initial dissemination or publication, accompanied by Form FDA 2253 (21 CFR 601.12(f)(4)).

 
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 or substantial clinical experience to support such claims (21 CFR 202.1(e)(6)).
 
Please submit an amendment to all pending supplemental applications for this BLA that include revised labeling incorporating a revised content of labeling that includes this change.
 
Postmarketing Studies Subject to Reporting Requirements of 21 CFR 601.70  
 
PEDIATRIC REQUIREMENTS
 
Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication(s) in pediatric patients unless this requirement is waived, deferred, or inapplicable. 
 
We are waiving the pediatric study requirement for ages 0 to < 6 months because this product does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients and is not likely to be used in a substantial number of infants < 6 months of age. Available data indicate that serum antibody responses to inactivated influenza vaccines in infants < 6 months of age are not as robust as in older children due to inherent immaturity of the immune system and interference from maternal antibody. 
 
We are deferring submission of your pediatric studies for ages 6 months to 35 months for this application because the product is ready for approval in persons 3 years of age and older and pediatric studies in ages 6 months to 35 months have not been completed.
 
Your deferred pediatric studies required under 505B(a) of the Federal Food, Drug, and Cosmetic Act are required postmarketing studies. The status of these postmarketing studies must be reported according to 21 CFR 601.70 and section 505B(a)(3)(B) of the Federal Food, Drug, and Cosmetic Act.  These required studies are listed below:
 
1.   Deferred pediatric study D-QIV-004 under PREA for active immunization for the prevention of disease caused by influenza A subtype viruses and type B viruses contained in Fluarix® Quadrivalent, in pediatric patients ages 6 months to 35 months of age. The final protocol has been reviewed by CBER and this study is currently ongoing.
 
Study Completion Date: October 2013
Final Report Submission: March 2014
 
Please submit the final study report to this BLA. 
 
 
AGREED UPON POSTMARKETING COMMITMENTS

We acknowledge your written commitment as described in your letter of December 10, 2012, as outlined below:

 
2.   To establish a pregnancy registry to prospectively collect data on spontaneously-reported exposures to Fluarix® Quadrivalent during pregnancy.  A protocol for this pregnancy registry will be submitted by April 30, 2013.  The pregnancy registry will be established by August 30, 2013 and annual reports will be submitted with the periodic safety update reports (PSURs) for Fluarix® Quadrivalent.  When the registry has collected data on the outcomes specified in the protocol for five years, GSK will submit a full study report 18 months from submission of the fifth annual PSUR.  After submission of the registry report, GSK will continue enrolling in the registry pending CBER review of the report and determination that the registry can be discontinued.
 
Please submit clinical protocols to your IND, with a cross-reference letter to this BLA, STN BL 125127. Submit all study final reports to your BLA, STN BL 125127. If the information in the final study report supports a change in the labeling, the final study report should be submitted as a supplement. We may also request a supplement if we think labeling changes are needed. Please use the following designators to label prominently all submissions, including supplements, relating to these postmarketing study commitments as appropriate:
 
  • Postmarketing Study Commitment Protocol
  • Postmarketing Study Correspondence
  • Postmarketing Study Commitment – Final Study Report
  • Supplement Contains Postmarketing Study Commitments – Final Study Report
 
In addition, for the deferred pediatric study (Study D-QIV-4), we request that you also use the following designation on all submissions:

 
  • Required Pediatric Assessment
 
For these postmarketing studies, which are subject to the reporting requirements of 21 CFR 601.70, you must describe the status in an annual report.  Please label your annual report as “Annual Status Report of Postmarketing Study Commitments.” The status report for each study should include:
 
o   information to identify and describe the postmarketing commitment,
o   the original schedule for the commitment,
o   the status of the commitment (i.e., pending, ongoing, delayed, terminated, or submitted), and
o   an explanation of the status including, for clinical studies, the patient accrual rate (i.e., number enrolled to date and the total planned enrollment).
 
 
As described in 21 CFR 601.70(e), we may publicly disclose information regarding these postmarketing studies on our web site (http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Post-marketingPhaseIVCommitments/default.htm). Please refer to the February 2006 “Guidance for Industry: Reports on the Status of Postmarketing Studies – Implementation of Section 130 of the Food and Drug Administration Modernization Act of 1997” (see http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM080569.pdf) for further information.
 
Postmarketing Studies not Subject to Reporting Requirements of 21 CFR 601.70  
 
We acknowledge your written commitment as described in your letter of November 15, 2012, as outlined below:
 
  1. ---------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------ ----------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
 
For each postmarketing commitment not subject to the reporting requirements of 21 CFR 610.70 you may report the status to FDA as a “PMC Submission – Status Update.” The status report for each commitment should include:
 
o   information to identify and describe the postmarketing commitment, and
o   the original schedule for the commitment and the status of the commitment (i.e., pending, ongoing, delayed, terminated, or submitted).
 
When you have fulfilled your commitment, please submit your final report as a PMC submission labeled prominently as follows: Final Study Report or Supplement Contains Postmarketing Study Commitment – Final Study Report.
 
We will include information contained in the above-referenced supplement in your biologics license application file.
 
                                                                       Sincerely yours,
 
 
 
                                                                        Wellington Sun, MD
                                                                        Director
                                                                        Division of Vaccines and
                                                                         Related Products Applications
                                                                        Office of Vaccines
                                                                         Research and Review
                                                                        Center for Biologics
                                                                          Evaluation and Research