August 3, 2004
Carol M. Moore
Vice President, Worldwide Regulatory Affairs
Bayer HealthCare LLC
800 Dwight Way
Berkeley, CA 94701-1986
Re: BLA STN #103332
Helixate FS [Antihemophilic Factor (Recombinant) Formulated with Sucrose]
Dear Ms. Moore:
The Advertising and Promotional Labeling Branch (APLB) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has reviewed a "Helixate FS Why Switch Flashcard" (102-6800) and a "Helixate FS Patient Guide Update" (102-7564) for Helixate FS [Antihemophilic Factor (Recombinant) Formulated with Sucrose] (copies enclosed) submitted by Bayer HealthCare LLC (Bayer) under cover of Form FDA 2253. The flashcard and patient guide misbrand Helixate FS under section 502(a) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 352(a)) and under 21 C.F.R. 201.6(a) because they contain false or misleading representations that Helixate FS is safer and better than has been demonstrated by substantial evidence or substantial clinical experience. Cf. 21 C.F.R. 202.1(e)(6)(i). The flashcard and patient guide could lead patients and health care practitioners to believe that your product is safer and better than has been demonstrated and, therefore, could encourage use of the product under conditions other than those for which FDA has found the product safe and effective.
According to the FDA-approved professional labeling (PI), Helixate FS is a dried concentrate produced by Baby Hamster Kidney cells into which the human factor VIII gene has been introduced. Bayer's revised process for manufacturing Helixate FS with sucrose eliminates the need to add human albumin during purification or in the final formulation. Helixate FS is indicated for the treatment of classical hemophilia (hemophilia A) in which there is a demonstrated deficiency of activity of the plasma clotting factor, FVIII.
Unsubstantiated Safety Claims
The flashcard and patient guide include the statement, "Unsurpassed viral safety," followed by text referring to its being formulated without human albumin. We are concerned that this claim could be interpreted to mean that no other hemophilia A therapy offers better viral safety than Helixate FS. FDA is unaware of substantial evidence or substantial clinical experience supporting this claim. To the extent that you may have such information, we invite you to submit it. In the absence of sufficient substantiation, the claim would be false or misleading, and the flashcard and patient guide would misbrand Helixate FS. 21 U.S.C. § 352(a); 21 C.F.R. 201.6(a). Cf. 21 C.F.R. 202.1(e)(6)(i).
Unsubstantiated Superiority Claims
The patient guide contains the text: "The smallest available diluent size--2.5 mL--for faster, easier infusions." The flashcard (102-6800) contains the statement: "The smallest diluent size available lets patients experience easier, faster infusions." These promotional materials thus suggest that no other Factor VIII product has a diluent size of 2.5 mL or smaller. This is false and misleading. Helixate FS has the same 2.5 mL diluent size as Kogenate FS, which is a Factor VIII product that Bayer also manufactures. (Aventis Behring distributes Helixate FS manufactured by Bayer, while Bayer both manufactures and distributes Kogenate FS.) Moreover, the dosage required for hemostasis and the rate of administration must be individualized according to the needs of the patient and the patient's individual response, which depend on many factors.
The materials suggest that Helixate FS is superior to other Factor VIII products because it can be infused into patients more quickly and more easily. FDA is not aware of substantial evidence or substantial clinical experience to support this claim. In the absence of sufficient substantiation, the claim would be false or misleading, and the flashcard and patient guide would misbrand Helixate FS. 21 U.S.C. § 352(a); 21 C.F.R. 201.6(a). Cf. 21 C.F.R. 202.1(e)(6)(i).
Conclusion and Requested Actions
The flashcard and patient guide misbrand Helixate FS within the meaning of section 502(a) of the Act (21 U.S.C. 352(a)) and 21 C.F.R. 201.6(a) because they represent that Helixate FS is safer than has been demonstrated by substantial evidence or substantial clinical experience and better than other drugs when this has not been proven.
We request that Bayer immediately cease the dissemination of promotional materials for Helixate FS that contain claims the same as, or similar to, those described above. Please submit a written response to this letter within ten (10) business days of the date of this letter, describing your intent to comply with this request, listing all promotional materials for Helixate FS 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 Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Compliance and Biologics Quality, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448, facsimile 301-827-3528. 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 Helixate FS comply with each applicable requirement of the Act and FDA implementing 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.
----- signature -----
Mary A. Malarkey
Director, Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
cc: Aventis Behring
A - Flashcard
B - Patient Guide