Our STN: BL 125163/253
ID Biomedical Corporation of Quebec
dba GlaxoSmithKline Biologicals
Attention: Judith A. Magner
2301 Renaissance Blvd., Building 510
King of Prussia, PA 19406
Dear Ms. Magner:
We have approved your request to supplement your biologics license application for Influenza Virus Vaccine (FluLaval®) to include a quadrivalent influenza virus vaccine formulation for the prevention of influenza disease in persons 3 years of age or older caused by influenza viruses contained in the vaccine. This quadrivalent formulation will be manufactured at your
---(b)(4)---, Quebec, Canada facility and will be designated FluLaval® Quadrivalent.
Additionally, we have approved your request to include data from the confirmatory clinical study to verify the clinical benefit of your Influenza Virus Vaccine. We licensed your Influenza Virus Vaccine under the accelerated approval regulations. Approval of this supplement fulfills your accelerated approval requirement (21 CFR 601.41) to conduct a clinical endpoint efficacy study of Influenza Virus Vaccine in children 3 to 8 years of age as stated in requirement number 1 of our approval letter of June 9, 2011, for supplement STN BL 125163/176.
The review of this product was associated with the following National Clinical Trial (NCT) numbers: NCT01196975, NCT01198756 and NCT01218308.
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 labelingshould be submitted as Product Correspondence to this biologics license applicationat 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 biologics license application that include revised labeling incorporating a revised content of labeling that includes these changes.
Postmarketing Studies Subject to Reporting Requirements of 21 CFR 601.70
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 in pediatric patients unless this requirement is waived, deferred, or inapplicable.
We are waiving the pediatric study requirement in infants from 0 to < 6 months of age, 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 study for 6 months to 35 months of age for this application because this product is ready for approval for use in persons 3 years of age and older and the pediatric study in younger children has not been initiated.
Your deferred pediatric study required under 505B(a) of the Federal Food, Drug, and Cosmetic Act is a required postmarketing study. The status of this postmarketing study must be reported according to 21 CFR 601.70 and section 505B(a)(3)(B) of the Federal Food, Drug, and Cosmetic Act. This required study and timeline described in your letter of August 14, 2013, are outlined below:
- Deferred pediatric study under PREA to evaluate the safety and immunogenicity of FluLaval® Quadrivalent in children 6 to 35 months of age.
|Final Protocol Submission Date:||June 30, 2014|
|Study Completion Date:||September 30, 2015|
|Final Report Submission:||March 31, 2016|
This product is appropriately labeled for use in persons 3 years of age and older. Therefore, no additional studies are needed in the pediatric group 3 to 17 years of age.
AGREED UPON POSTMARKETING COMMITMENTS
We acknowledge your commitment described in your letter of August 14, 2013, outlined below:
- To establish a pregnancy registry that will enroll women exposed to FluLaval® Quadrivalent during pregnancy and collect data on their outcomes and newborn health status. Annual reports for this registry will be submitted with the Periodic Benefit-Risk Evaluation Report (PBRER)) for FluLaval® Quadrivalent. When the registry has collected data on the outcomes specified in the protocol for five years, you will submit a final study report. After submission of the registry report, you will continue enrolling in the registry pending our review of the report and determination that the registry can be discontinued.
|Final Protocol Submission Date:||October 31, 2013|
|Study Completion Date:||November 30, 2018|
|Final Report Submission:||March 31, 2020|
Please submit clinical protocols to your IND, and a cross-reference letter to your biologics license application, STN BL 125163. Submit nonclinical and chemistry, manufacturing, and controls protocols and all final study reports to your biologics license application,
STN BL 125163. 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 determine that labeling changes are necessary. 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
For each postmarketing study subject to the reporting requirements of 21 CFR 601.70, you must describe the status in an annual report on postmarketing studies for this product. Label your annual report an “Annual Status Report of Postmarketing Study Commitments.” The status report for each study should include:
- information to identify and describe the postmarketing commitment,
- the original schedule for the commitment,
- the status of the commitment (i.e., pending, ongoing, delayed, terminated, or submitted), and
- 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.
When you have fulfilled your commitment, submit your final report as a PMC Submission – 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.
Wellington Sun, MD
Division of Vaccines and
Related Products Applications
Office of Vaccines
Research and Review
Center for Biologics
Evaluation and Research
Attachment: Approved Final Draft Labeling