April 25, 2008
VIA FACSIMILE AND CERTIFIED MAIL
RETURN RECEIPT REQUESTED
Mr. Mark W. Gauthier
Associate Director Regulatory Affairs
1201 Eastlake Avenue East
Seattle, WA 98102
STN: BL 125248/0
RecothromT (Thrombin, Topical (Recombinant))
Dear Mr. Gauthier:
The Advertising and Promotional Labeling Branch (APLB) in the Food and Drug Administration's (FDA's) Center for Biologics Evaluation and Research (CBER) has reviewed information on your website www.zymogenetics.com, including a press release for Recothrom (Thrombin, Topical (Recombinant)). This promotional material is false or misleading because it omits material facts about Recothrom. Thus, the promotional material misbrands your Recothrom product in violation of the Federal Food, Drug, and Cosmetic Act (Act), 21 U.S.C. §§ 352(a) and 321(n).
Recothrom is a coagulation protein produced via recombinant DNA technology from a genetically modified Chinese Hamster Ovary (CHO) cell line. The "Indications and Usage" section of the FDA-approved labeling (PI) states:
RECOTHROM is indicated as an aid to hemostasis whenever oozing blood and minor bleeding from capillaries and small venules is accessible and control of bleeding by standard surgical techniques is ineffective or impractical.
RECOTHROM may be used in conjunction with an absorbable gelatin sponge, USP.
Omission of Material Facts
In the "Newsroom" portion of your website, www.zymogenetics.com, the press release entitled "FDA Approves ZymoGenetics' RECOTHROMT Thrombin, topical (Recombinant)", dated January 17, 2008, contains the following statement:
"A Phase 3 pivotal clinical trial showed that RECOTHROM had comparable efficacy and a significantly lower incidence of antibody formation compared to the commercially available bovine thrombin product."
This statement is false or misleading because it suggests that Recothrom is safer than the bovine thrombin product due to a lower incidence of antibody formation in the patients who took the Recothrom. However, this statement excludes important contextual information necessary to understand the limitation of this finding. In determining whether promotional materials are misleading, FDA takes into consideration not only the representations made or suggested in such materials, but also the extent to which the promotional materials fail to reveal facts that are material in light of these representations, or that are material with respect to the consequences which may result from the use of the product (21 U.S.C. §§ 352(a) and 321(n)).
Indeed, according to the "Immunogenicity" section of the Recothrom PI, the development of antibodies in either group did not lead to any adverse events such as excessive bleeding. In addition, according to the "Adverse Reactions" section of the PI, the incidences of pre-specified adverse events were similar between Recothrom and bovine thrombin.
Conclusion and Requested Actions
For reasons discussed above, your promotional material misbrands Recothrom within the meaning of 21 U.S.C. §§ 352(a) and 321(n) of the Act.
We request that ZymoGenetics immediately cease the dissemination of the violative promotional material for Recothrom, as described above. 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 materials for Recothrom and explaining your plan for discontinuing use of such materials. Please direct your response to Ms. Ele Ibarra-Pratt, RN, MPH, Branch Chief, at 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 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 the promotional material for your products comply with each applicable requirement of the Act and implementing regulations.
/Robert A. Sausville/
Robert A. Sausville
Director, Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
Enclosure: website: www.zymogenetics.com