Our STN: BL 103914/5733
Sanofi Pasteur Inc.
Attention: Michael F. Stirr
Swiftwater, PA 18370
Dear Mr. Stirr:
We have approved your request to supplement your biologics license application for Influenza Vaccine (Fluzone®) manufactured at your Swiftwater, PA and ------(b)(4)------ facilities, to include a quadrivalent intradermal formulation of influenza vaccine (Fluzone Intradermal Quadrivalent) for use in persons 18 through 64 years of age.
The review of this product was associated with the following National Clinical Trial (NCT) number: NCT01712984
Under 21 CFR 201.57(c)(18), patient labeling must be reprinted at the end of the package insert. We request that the text of information distributed to patients be printed in a minimum of 10-point font.
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 and FDA Form 2567 as appropriate.
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 Advertising and Promotional Labeling Branch at the following address:
Food and Drug Administration
Center for Biologics Evaluation and Research
Document Control Center
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
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)).
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 for this application 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 pediatric patients.
Available data indicate that the immune response to inactivated influenza vaccines in infants < 6 months of age is not as robust as in older children due to immaturity of the immune response and interference from maternal antibody. For the age group 6 months through 17 years of age, Fluzone Intradermal Quadrivalent provides no meaningful therapeutic benefit over licensed influenza vaccines and is not likely to be used in a substantial number of infants and children because of the increased risk for local reactogenicity.
Postmarketing Studies subject to reporting requirements of 21 CFR 601.70.
We acknowledge your written commitment as described in your letter of Dec. 9, 2014, as outlined below:
- To establish a pregnancy registry that will enroll women exposed to Fluzone Intradermal 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 that includes all other Fluzone® influenza vaccines. When the registry has collected data on the outcomes specified in the protocol for 4 years, Sanofi will submit a final study report including information for both Fluzone Intradermal Quadrivalent and Fluzone Quadrivalent vaccine (administered intramuscularly). After submission of the registry report, Sanofi will continue enrolling in the registry pending CBER review of the report and determination that the registry can be discontinued.
Final protocol submission date: June 30, 2015
Study/trial completion date: August 30, 2019
Final Report Submission date: December 31, 2020
Please submit clinical protocols to your IND, with a cross-reference letter to this biologics license application (BLA), STN BL 103914/0. Submit nonclinical and chemistry, manufacturing, and controls protocols and all study final reports to your BLA STN BL 103914/0. 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
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.
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