Vaccines, Blood & Biologics

August 31, 2005 Approval Letter - Fluarix

Public Health Service
Food and Drug Administration
Rockville, MD 20852-1448

August 31, 2005

Our STN: BL 125127 / 0

GlaxoSmithKline Biologicals
Attention: Ms. Teresa Ward
Director, Vaccines Establishment
U.S. Regulatory Affairs
2301 Renaissance Boulevard
Building 510, P.O. Box 61540
King of Prussia, PA 19406-2772

Dear Ms. Ward:

We have approved your Biologics License Application (BLA) for Influenza Virus Vaccine according to the regulations for accelerated approval effective this date. You are hereby authorized to introduce or deliver for introduction into interstate commerce, Influenza Virus Vaccine, under your existing Department of Health and Human Services U.S. License No. 1617. Influenza Virus Vaccine is indicated for active immunization of adults 18 years of age and older against influenza disease caused by influenza virus types A and B.

Under this authorization you are approved to manufacture Influenza Virus Vaccine at Sächsisches Serumwerk (SSW), a subsidiary of GlaxoSmithKline Biologicals (GSK), in Dresden, Germany. Final product filling, labeling, and packaging will be performed by GlaxoSmithKline Biologics in ---------------------------. You may label your product with the proprietary name Fluarix. The vaccine will be marketed in 0.5 mL single-dose pre-filled Tip-Lok syringes.

The dating period for Influenza Virus Vaccine shall be 12 months from the date of manufacture of the filled final container vaccine when stored at 2-8oC, but not beyond June 30th of the given influenza season. The 12-month shelf life is inclusive of the time that the product is held in filled final containers at 2-8oC prior to packaging. The date of manufacture shall be defined as the date on which the trivalent vaccine is filled. Potency testing performed on the final filled container must commence within 6 weeks after filling. Any extension of the dating period will require the submission and approval of supportive data as a prior approval supplement to your BLA.

Please submit concentrates and final bulk samples of the product together with lot release protocols in the proper format showing results of all applicable tests. You may not distribute any lots of product until you receive a notification of release from the Director, Center for Biologics Evaluation and Research (CBER).

You must submit information to your BLA for our review and written approval under 21 CFR 601.12 for any changes in the manufacturing, testing, packaging or labeling of Influenza Virus Vaccine, or in the manufacturing facilities.

All applications for new active ingredients, new dosage forms, new indications, new routes of administration, and new dosing regimens are required to contain an assessment of the safety and effectiveness of the product in pediatric patients unless this requirement is waived or deferred. We have reviewed your submission dated May 25, 2005, and agree that a deferral of your pediatric studies for Fluarix in children less than 18 years of age is justified as you are pursuing with due diligence a pediatric indication for Fluarix.

Postmarketing Studies subject to reporting requirements of 21 CFR 601.70

Products approved under the accelerated approval regulations, 21 CFR 314.510, require further adequate and well-controlled confirmatory clinical studies to verify and describe clinical benefit. We remind you of your postmarketing study commitments specified in your submission dated May 25, 2005. These commitments, along with any completion dates agreed upon, are listed below.


  1. To conduct Study Fluarix US-003, a comparative safety and immunogenicity study of Fluarix and Fluzone in adults 18 years of age and older. The study will be initiated no later than November 2005. The final study report will be submitted by December 2006.


  2. To conduct Study Fluarix US-004, a placebo-controlled clinical endpoint efficacy study of Fluarix in subjects 18-64 years of age. The study will be initiated no later than November 2005. The final study report will be submitted by December 2006.

We request that you submit clinical protocols to your IND ---------; please provide a cross-reference letter to this BLA.

Postmarketing Studies not subject to reporting requirements of 21 CFR 601.70


Please submit non-clinical and chemistry, manufacturing, and controls protocols and all study final reports to your BLA, STN BL 125127. Please use the following designators to label prominently all submissions, including supplements, relating to these postmarketing study commitments as appropriate:


  • Postmarketing Study Protocol
  • Postmarketing Study Final Report
  • Postmarketing Study Correspondence
  • Annual Report on Postmarketing Studies

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. 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 ( Please refer to the April 2001 Draft 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 for further information.

Please submit adverse experience reports in accordance with the adverse experience reporting requirements for licensed biological products (21 CFR 600.80) and distribution reports as described in (21 CFR 600.81). Under 21 CFR 600.80(c)(2) [Periodic Adverse Experience Reports], you must report each adverse experience not reported under paragraph (c)(1)(i) of this section at quarterly intervals for the first 3 years following approval, and then at annual intervals. Since your product is characterized as a vaccine, you must also submit these reports to the Vaccine Adverse Event Reporting System (VAERS) using the pre-addressed form VAERS-1.

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.

Please submit all final printed labeling and implementation information on FDA Form 356h. Please provide a PDF-format electronic copy as well as one original paper copy.

Please note that the accelerated approval regulation concerning promotional materials (21 CFR 601.45) stipulates that all advertising and promotional labeling items that GSK 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 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. Two copies of all final advertising and promotional labeling materials should be submitted at the time of initial dissemination, accompanied by FDA Form 2253.

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 submitted data to support such claims to us and received CBER approval for such claims.

If you have any questions, please contact Dr. Sara Gagneten at 301-827-3070.

Sincerely yours,

--- signature ---

Norman W. Baylor, Ph.D.
Office of Vaccines Research and Review
Center for Biologics Evaluation and Research

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