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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Vaccines

May 9, 2011 Approval Letter - Fluzone Intradermal

Our STN: BL 103914/5369

Sanofi Pasteur Inc.
Attention: Joseph Quinn
Discovery Drive
Swiftwater, PA 18370
 

Dear Mr. Quinn: We have approved your request to supplement your biologics license application (BLA) for Influenza Virus Vaccine to include a formulation for intradermal administration. 

Under license 1725, you are approved to manufacture this formulation of Influenza Virus Vaccine for intradermal administration at your facility in Swiftwater, PA, and fill into final containers at your facility in -------(b)(4)--------. You may label this formulation of your product with the proprietary name Fluzone® Intradermal and market it in Becton Dickinson --(b)(4)-- 0.1 mL single-dose pre-filled syringes.

Fluzone Intradermal is an inactivated influenza virus vaccine indicated for active immunization against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine. Fluzone Intradermal is approved for use in adults 18 through 64 years of age.

We did not refer your supplement to the Vaccines and Related Biological Products Advisory Committee because our review of information submitted in your supplement, including the design and results of the clinical trials did not raise concerns or controversial issues which would have benefited from an advisory committee discussion.

The dating period for Fluzone Intradermal shall be 9 months from the date of manufacture of the final container vaccine, but not to exceed June 30th of the influenza season for which it was formulated when stored at 2-8°C (36-46°F). The date of manufacture shall be defined as the start date of filling into final containers. Any extension of the dating period will require the submission and approval of supportive data as a prior approval supplement to your BLA; ongoing stability data may be submitted as product correspondence as it becomes available.

You must submit reports of biological product deviations under 21 CFR 600.14. You should promptly identify and investigate all manufacturing deviations, including those associated with processing, testing, packing, labeling, storage, holding and distribution. If the deviation involves a distributed product, may affect the safety, purity, or potency of the product, and meets the other criteria in the regulation, you must submit a report on Form FDA-3486 to the Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, MD 20852-1448, or electronically to http://www.fda.gov/cber/biodev/biodev.htm.

The review of this product was associated with the following National Clinical Trial (NCT) number(s): NCT00170547, NCT00772109, NCT01011049, NCT00388583, NCT00551031, NCT00775450, NCT00391391, NCT00623181, NCT00703651 and NCT00258934

Under 21 CFR 201.57(c)(18), patient labeling must be reprinted at the end of or accompany prescription drug labeling. 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 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 these changes.

ADVERSE EVENT REPORTING

You must submit adverse experience reports in accordance with the adverse experience reporting requirements for licensed biological products (21 CFR 600.80) and you must submit distribution reports (as described in 21 CFR 600.81). You should submit these reports to the Vaccine Adverse Event Reporting System (VAERS), P.O. Box 1100, Rockville, MD 20849-1100, using the pre-addressed form VAERS-1 (http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation
/Guidances/Vaccines/UCM164319.pdf
). Per 21 CFR 600.2(f), please refer to http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm106001.htm for updated mailing address information.

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 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, Fluzone Intradermal 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 submission dated May 9, 2011, as outlined below:

1. You have agreed to monitor the safety of Fluzone Intradermal administered to pregnant women by establishing a Pregnancy Registry designed as an observational, open-ended, postmarketing safety surveillance program. 

Final protocol submission date: July 15, 2011

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. 
 

Postmarketing Studies not subject to reporting requirements of 21 CFR 601.70. 
We acknowledge your written commitment as described in your submission dated May 9, 2011, as outlined below:

2. ------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

We request that you submit information concerning nonclinical and chemistry, manufacturing, and control postmarketing commitments and final reports to your BLA STN BL 103914/0. 

Please use the following designators to label prominently all submissions, including supplements, relating to these postmarketing study commitments as appropriate:
 

  • Postmarketing Study Correspondence
  • Postmarketing Study Commitment – Final Study Report
  • Supplement Contains Postmarketing Study Commitment – Final Study Report
     

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:
 

  • 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, submit your final report as 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.

Sincerely yours,
 

Wellington Sun, M.D.
Director
Division of Vaccines and
Related Products Applications
Office of Vaccines
Research and Review
Center for Biologics
Evaluation and Research
 

Attachment: Approved Final Draft Labeling