August 22, 2011
VIA FACSIMILE AND UPS
Joseph H. Quinn
Senior Director, Regulatory Affairs U. S.
and Authorized Official
sanofi pasteur Inc.
Swiftwater, PA 18370
Re: Fluzone (Influenza Virus Vaccine)
BLA STN #103914
Dear Mr. Quinn:
The Advertising and Promotional Labeling Branch (APLB) in the Food and Drug Administration’s Center for Biologics Evaluation and Research has reviewed your Fluzone High-Dose Refreshed Detail Aid (MKT22193) submitted July 15, 2011 under cover of Form FDA 2253 for your product Fluzone [Influenza Virus Vaccine]. These materials are intended for use in the 2011-2012 influenza season.
This promotional material is false, misleading, or lacking in fair balance because it omits and minimizes the risks associated Fluzone. Therefore, these materials misbrand Fluzone under Sections 502(a) and 201(n) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. §352(a) and §321(n), and FDA implementing regulations, Cf. 21 CFR §202.1(e)(6)(xviii) and (7)(viii).
According to the FDA-approved prescribing information (PI) for Fluzone, including Fluzone High-Dose and Fluzone Intradermal, the vaccines are indicated for active immunization against influenza disease caused by virus subtypes A and type B contained in the vaccines. Fluzone High-Dose is approved for use in persons 65 years of age and older, and Fluzone Intradermal is approved for use in persons 18 through 64 years of age. Data demonstrating a decrease in influenza disease after vaccination with Fluzone High-Dose are not available.
A severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine, including egg protein, or to a previous dose of any influenza vaccine is a contraindication to administration of Fluzone.
Fluzone has two warnings: (1) If Guillain-Bare syndrome (GBS) has occurred within 6 weeks of previous influenza vaccination, the decision to give Fluzone should be based on careful consideration of the potential benefits and risks and (2) the prefilled syringe tip caps of Fluzone may contain natural rubber latex which may cause allergic reactions in latex sensitive individuals.
APLB sent Advisory letters to Sanofi Pasteur on May 5, May 6, May 24, June 7, July 19, and August 4, 2011, regarding the omission of information from the contraindications. Specifically, the phrase “or to a previous dose of any influenza vaccine,” was omitted from the contraindication.
On March 15 and May 6, 2011, APLB sent Sanofi Pasteur advisory letters regarding the presentation of important safety information in Fluzone materials. These letters informed Sanofi Pasteur
The sales aid is lacking fair balance because it fails to present information relating to risk information with a prominence and readability reasonably comparable to the presentation of effectiveness. Specifically, all of the risk information is concealed inside the back cover of this six-page sales aid. In addition, the risk information is printed on less than half a page and sandwiched between the indication and references. (March 15, 2011)
The journal ad is lacking fair balance because it fails to present information relating to risk information with a prominence and readability reasonably comparable to the presentation of effectiveness. Specifically, the safety profile information is printed on less than 1/8 of the page and is sandwiched between the efficacy data and ordering information and references. (May 6, 2011)
Omission and Minimization of Risk Information
Promotional materials are misleading if they fail to reveal facts that are material in light of representations made by the materials or with respect to consequences that may result from the use of the product as recommended or suggested by the materials, and if they fail to present information about risks associated with a product with a prominence and readability reasonably comparable with the presentation of information relating to the effectiveness of the product.
The “Important Safety Information” for Fluzone must include the contraindications, warnings, and the most common adverse reactions. Your Fluzone High-Dose Refresher Detail Aid fails to include the information from the contraindication that the vaccine should not be administered to anyone who has had a severe allergic reaction after a previous dose of influenza vaccine.
In addition, on each page or two-page spread of your detail aid, there is a directive to “Please see Important Safety Information on back cover;” however, the back cover emphasizes efficacy information with the prominent headline
Intended to strengthen the immune response to influenza in adults 65 years of age and older.
followed by bulleted statements regarding the immunogenicity of Fluzone High Dose.
In addition, the “important safety information” on the back cover is printed on less than half a page and is sandwiched between the indication and references. The risk information is further minimized by a distracting two-tone purple graphic on the bottom of the page.
Conclusion and Requested Actions
For the reasons discussed above, your promotional material misbrands Fluzone under sections 502(a), 502(f)and 201(n) of the Act, 21 U.S.C. §352(a), §352(f) and §321(n), and FDA implementing regulations, Cf. 21 CFR 202.1(e)(6)(xviii) and (7)(viii).
We request that Sanofi Pasteur immediately cease the dissemination of this violative promotional material for Fluzone High Dose, as well as any promotional materials for Fluzone with the same or similar claims and representations. Please submit a written response within ten (10) business days of the date of this letter, stating whether you intend to comply with this request, listing all violative promotional materials for Fluzone, and explaining your plan for discontinuing use of such materials. Please direct your response to Lisa Stockbridge, Ph. D., Branch Chief at the Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Compliance and Biologics Quality, Division of Case Management, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448. In all future correspondence regarding this matter, please refer to the BLA/STN number. We remind you that only written communications are considered official responses.
The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Fluzone High Dose comply with each applicable requirement of the Act and FDA implementing regulations.
Robert A. Sausville
Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research