Violative Advertising and Promotional Labeling Letter
Typhoid Vi Polysaccharide Vaccine (Typhim Vi)
(Aventis Pasteur Inc)
April 2, 2004
Luc Kuykens, MD, MPH, DTM
Vice President, Regulatory Affairs
North America
Aventis Pasteur Inc.
Discover Drive
Swiftwater, PA 18370
Re: BLA STN #103936
Typhim Vi (Typhoid Vi Polysaccharide Vaccine)
Dear Dr. Kuykens:
The Advertising and Promotional Labeling Branch (APLB) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has reviewed a flashcard (MKT7836) for Typhim Vi (Typhoid Vi Polysaccharide Vaccine) (copy enclosed). This flashcard violates section 502(a) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. § 352(a)) because it contains false or misleading comparative claims in violation of 21 C.F.R. § 201.6(a), cf. 21 C.F.R. § 202.1(e)(6)(ii), and a false or misleading effectiveness claim. Cf. 21 C.F.R. § 202.1(e)(6)(i). These materials mislead both consumers and professionals to believe that Typhim Vi is safer or more effective than has been demonstrated by substantial evidence or substantial clinical experience.
Background
Typhim Vi is a sterile solution containing the cell surface Vi polysaccharide extracted from Salmonella typhi Ty2 strain and is for intramuscular use. According to the approved package insert (PI), Typhim Vi is indicated for active immunization against typhoid fever for persons two years of age or older. The PI further states:
"Based on the available efficacy data, vaccination with Typhim Vi may not be expected to protect 100% of susceptible individuals."
"An optimal reimmunization schedule has not been established. Reimmunization every two years under conditions of repeated or continued exposure to the S. typhi organism is recommended at this time."
False or Misleading Comparative Claims
This flashcard contains a comparison chart of two typhoid vaccines, Typhim Vi and Ty21a. Specifically, this chart contains comparisons of adverse reactions, efficacy trials, booster time periods, and contraindications. FDA is unaware of any direct comparative clinical trials of these products to support the presentation of comparative safety or effectiveness data. In fact, your approved PI specifically states, "Controlled comparative efficacy studies of Typhim Vi and other types of typhoid vaccines have not been performed."
In the absence of direct comparative clinical trials, the presentation of these data for the competing product, Ty21a, leads the reader to believe that such data result from comparative studies and can be used to make choices between products when, in fact, these data represent results from studies of each product in entirely different populations. For example, protective efficacy for Typhim Vi was studied in Nepal and South Africa. In contrast, Ty21a was studied in Egypt and Chile. Presenting results in a comparative format from these trials, conducted in such different populations, is not valid and is misleading. In the absence of such data, this flashcard misbrands Typhim Vi because it presents false or misleading representations with respect to another drug. 21 C.F.R. § 201.6(a); cf. 21 C.F.R. § 202.1(e)(6)(ii).
In addition, you have falsely stated that oral polio vaccine is a contraindication for Ty21a. In fact, the approved PI for Ty21a specifically provides for concomitant administration of oral polio vaccine with Ty21a. Therefore, that statement also renders Typhim Vi misbranded in that it is a false or misleading representation with respect to another drug, 21 C.F.R. § 201.6(a).
False or Misleading Effectiveness Claim
The reverse side of the referenced flashcard contains the statement, "Provides typhoid protection that requires just 1 shot." The placement of this statement without the mention of the need for a booster in close proximity leads the reader to believe that the shot gives complete protection with just one dose.
This statement, as it is presently written, is false or misleading because it implies that Typhim Vi is effective in protecting against typhoid without the need for reimmunization. Cf. 21 C.F.R. § 202.1(e)(6)(i). Your approved PI specifically states, "An optimal reimmunization schedule has not been established. Reimmunization every two years . is recommended at this time." Your PI further states, "Based on the available efficacy data, vaccination with Typhim Vi may not be expected to protect 100% of susceptible individuals."
We would recommend this statement be revised to state, "Provides typhoid protection for 2 years [emphasis added] that requires just 1 shot."
Conclusion and Requested Actions
The flashcard is false or misleading because it presents false or misleading representations with respect to another drug in violation of 21 C.F.R. § 201.6(a), cf. 21 C.F.R. § 202.1(e)(6)(ii), and because it suggests that Typhim Vi is effective against typhoid without the need for reimmunization, cf. 21 C.F.R. § 202.1(e)(6)(i). Therefore, the flashcard misbrands Typhim Vi within the meaning of 502(a) of the Act (21 U.S.C. § 352(a)).
APLB requests that Aventis Pasteur immediately cease disseminating promotional materials for Typhim Vi that contain claims the same as, or similar to, those described above. Please submit a written response to this letter within 10 business days of the date of this letter, describing your intent to comply with this request, listing all promotional materials for Tyhim Vi that contain claims the same as or similar to those described above, and explaining your plan for discontinuing use of such materials.
Please direct your response to Mr. Glenn N. Byrd, Chief, APLB, at the following address:
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 number. We remind you that only written communications are considered official. Should you have any questions or concerns involving this matter, please contact Nancy Chamberlin, Pharm.D., Regulatory Review Officer at 301-827-3028.
This letter is not intended to be an all-inclusive list of deficiencies associated with your promotion of the above product. It is your responsibility to ensure that all materials distributed within the United States comply with each applicable requirement of the Act and FDA regulations. If you choose to revise your promotional materials, APLB is willing to assist you in assuring that your revised materials comply with applicable provisions of the Act by reviewing your revisions before you use them in promotion.
Sincerely,
----- signature -----
Mary A. Malarkey, Director
Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research