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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Vaccines

December 23, 2009 Approval Letter - Fluzone High-Dose

Department of Health Human Services
Public Health Service
Food and Drug Administration
Rockville, MD 20852-1448

Our STN: BL 103914/5240

Sanofi Pasteur Inc.
Attention: Joseph H. 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 high dose formulation according to the regulations for accelerated approval effective this date.

Under license 1725, you are approved to manufacture this high dose formulation of Influenza Virus Vaccine at your facility in Swiftwater, PA. You may label this formulation of your product with the proprietary name Fluzone® High-Dose and market it in 0.5 mL preservative-free single dose prefilled syringes.

The Fluzone High-Dose formulation of Influenza Virus Vaccine is an inactivated influenza virus vaccine, indicated for active immunization of adults 65 years of age and older against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine. This indication is based on the immune response elicited by Fluzone High-Dose; there have been no controlled clinical studies demonstrating a decrease in influenza disease after vaccination with Fluzone High-Dose.

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 clinical study design and trial results, did not raise concerns or controversial issues which would have benefited from an advisory committee discussion.

The dating period for Fluzone High-Dose 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 date on which this vaccine is filled. 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.

Please note that the accelerated approval regulation concerning promotional materials (21 CFR 601.45) stipulates that all advertising and promotional labeling items that Sanofi Pasteur Inc. wishes to distribute in the first 120 days following approval, must have been received by FDA prior to the approval date. After approval, promotional items intended for dissemination after the first 120 days following approval should be submitted to the FDA 30 days prior to the anticipated distribution date. Please submit these materials with Form FDA 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448. Two copies of all final advertising and promotional labeling materials should be submitted at the time of initial dissemination, accompanied by Form FDA 2253.

Please submit all final printed labeling at the time of use and include implementation information on FDA Form 356h. Please provide content of 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.

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.

ACCELERATED APPROVAL REQUIRED STUDY
Products approved under the accelerated approval regulations, 21 CFR 601.41, require further adequate and well-controlled confirmatory clinical studies to verify and describe clinical benefit. We remind you of your post-marketing study commitments specified in your submission dated December 17, 2009. This commitment, along with the agreed upon completion dates, is listed below.

  1. Sanofi Pasteur Inc. agrees to submit the results of the ongoing Study No. FIM07, an active-controlled clinical endpoint efficacy and safety study of Fluzone High-Dose compared to standard dose Fluzone in 27,000 – 30,000 adults 65 years of age and older. If the attack rate of influenza in a season is lower than expected, participant enrollment will be extended to an additional season. The final study report for three seasons will be submitted by February 28, 2013.

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 ages 0 to 6 months because the product fails to represent a meaningful therapeutic benefit over existing therapies for pediatric patients in this age group and is not likely to be used in a substantial number of pediatric patients in this age group. Fluzone High-Dose (60 µg HA/strain/0.5 mL) is intended for adults 65 years of age and older because immune responses to inactivated influenza vaccines at the standard dose of 15 µg HA/strain/0.5 mL are lower than those in younger adults. Standard dose Fluzone is appropriately labeled for use in ages 6 months to 18 years for this indication. Therefore, no additional studies are needed in pediatric populations.

Postmarketing Studies not subject to reporting requirements of 21 CFR 601.70.
We acknowledge your written commitment as described in your submission dated December 17, 2009, as outlined below:

  1. ------------(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------.

We will include information contained in the above-referenced supplement in your biologics license application file.

Sincerely yours,

--signature--

Wellington Sun, MD
Division Director
Division of Vaccines and Related Product Application
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research

Attachment: Approved Final Draft Labeling

 

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