April 13, 2006
VIA FACSIMILE AND CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Director, Global Brand Management
Wyeth Pharmaceuticals, Inc.
P.O. Box 8299
Philadelphia , PA 19101
Re: BLA STN 103779/5193
ReFacto® Antihemophilic Factor (Recombinant)
Dear Ms. Holston:
The Office of Compliance and Biologics Quality (OCBQ) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has reviewed your consumer-directed brochure titled "Bob's World" (115571-01) submitted on October 18, 2005, by your firm under cover of Form FDA 2253. This brochure is false or misleading under S ection 502(a) of the Federal Food, Drug, and Cosmetic Act (Act), 21 U.S.C. §§ 352(a), because it makes unsubstantiated safety claims that ReFacto® Antihemophilic Factor (Recombinant) is safer than has been demonstrated by substantial evidence or substantial clinical experience. By promoting unsubstantiated safety claims, you are potentially encouraging the unsafe use of ReFacto.
The Indications and Usage section of the FDA-approved labeling (PI) for ReFacto states the following :
ReFacto is indicated for the control and prevention of hemorrhagic episodes and for surgical prophylaxis in patients with hemophilia A (congenital factor VIII deficiency or classic hemophilia).
ReFacto is indicated for short-term routine prophylaxis to reduce the frequency of spontaneous bleeding episodes. The effect of regular routine prophylaxis on long-term morbidity and mortality is unknown.
ReFacto can be of a significant therapeutic value for treatment of hemophilia A in certain patients with inhibitors to factor VIII. In clinical studies of ReFacto, study subjects who developed inhibitors on study continued to manifest a clinical response when inhibitor titers were < 10 BU. When an inhibitor is present, the dosage requirement of factor VIII is variable. The dosage can be determined only by a clinical response and monitoring of circulating factor VIII levels after treatment.
The PI also includes detailed risk information including contraindications, warnings, precautions, and adverse reactions.
Unsubstantiated Safety Claims
Your consumer-directed brochure, "Bob's World," contains a section titled, "Where can I find recombinant clotting factor products?" Within this section is a sub-section titled "Pathogen Safety" for ReFacto. The following claims are presented in normal text in the body of this subsection:
"ReFacto is manufactured with state-of-the-art techniques to optimize pathogen (eg. viruses and prions) safety."
"Recent studies by Wyeth have shown that at least 2 steps in the ReFacto manufacturing process significantly reduced the number of prion particles that were added to a test sample in an experimental system. This further supports the pathogen safety of the ReFacto manufacturing process, which should reassure consumers. This means that there is less chance of contamination by pathogens that may be found in products made from blood. "
"In addition, the solvent-detergent method of manufacturing ReFacto provides complete and immediate inactivation of West Nile Virus."
These claims suggest that ReFacto is safer than has been demonstrated by substantial evidence or substantial clinical experience. Cf. 21 CFR 202.1(e)(6)(i). First, since a claim of prion removal needs to be supported by results from a validated TSE infectivity assay, your claim of "optimize pathogen (... prion) safety" is not substantiated. Second, FDA is not aware of any data to support your claims regarding prion safety or that the "solvent-detergent method of manufacturing ReFacto provides complete and immediate inactivation of West Nile Virus." If you have data consisting of substantial evidence or substantial clinical experience to support your claims, please submit the data to CBER for review.
Conclusion and Requested Action
Your consumer-directed brochure misbrands ReFacto within the meaning of section 502(a) of the Act, 21 U.S.C. §§ 352(a), because it presents unsubstantiated safety claims and is therefore false or misleading.
We request that Wyeth Pharmaceuticals immediately cease the dissemination of the violative promotional materials for ReFacto as described above. Please submit a written response to this letter 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 ReFacto such as the brochure described above, and explaining your plan for discontinuing use of such materials. Please direct your response to the Food and Drug Administration, Center for Biologics Evaluation and Research, Office of Compliance and Biologics Quality, HFM-602, 1401 Rockville Pike, Rockville, Maryland 20852-1448. In all future correspondence regarding this matter, please refer to the BLA/STN numbers. 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 ReFacto 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.
Robert A. Sausville
Director, Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
Enclosures: Consumer-Directed Brochure "Bob's World" (115571-01)