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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Antithrombin III, Human (Thrombate III)

September 5, 2008

VIA FACSIMILE AND CERTIFIED MAIL
RETURN RECEIPT REQUESTED

Mary Ann Lamb, Ph.D.
Vice President
Regulatory Affairs
Talecris Biotherapies, Inc.
8368 US Highway 70W
Clayton , NC 27520

Re:BLA STN #103196/5286
Thrombate III (Antithrombin III, Human)

Dear Dr. Lamb:

Through routine monitoring and surveillance, the Advertising and Promotional Labeling Branch (APLB) of the Food and Drug Administration’s Center for Biologics Evaluation and Research has reviewed sell sheet TH50-0807 (STN 103196/5286) for Thrombate III (Antithrombin III, Human) submitted by Talecris Biotherapies, Inc. (Talecris) under cover of Form FDA 2253. This sell sheet misbrands Thrombate III under sections 502(a) of the Federal Food, Drug, and Cosmetic Act (Act) (21 U.S.C. §352(a)), because it makes misleading superiority and safety claims (Cf. 21 CFR 202.1(e)(6)(i) and (e)(6)(ii)).

The FDA-approved professional labeling (PI) for Thrombate III states that it is indicated for the treatment of patients with hereditary antithrombin III (AT) deficiency in connection with surgical or obstetrical procedures or when they suffer from thromboembolism. These are specific high risk situations for patients with clotting deficiencies. To underscore this limited indication, the Indications and Usage section describes how to determine accurately the existence of hereditary AT deficiency.

Misleading Superiority Claims

The sell sheet presents safety and efficacy superiority claims for Thrombate III versus fresh frozen plasma (FFP) based on comparison of Thrombate III’s PI with anecdotal evidence. There are no adequate and well-controlled clinical trials or substantial clinical experience to support such superiority claims. Cf. 21 CFR 202.1(e)(6)(ii).

Specifically, the backside of the sell sheet includes a table comparing Thrombate III and FFP (fresh frozen plasma). The headings for the table read:

  • "Thrombate III … the Necessary Therapy"
  • "Fresh frozen plasma (FFP) is contraindicated for a coagulopathy when the missing protein is available as a concentrate."

The table continues with the comparison of Thrombate III and FFP on efficacy, dosing, "safety processing," adverse events, side effects, storage, and "convenience." The overall presentation of the table misleadingly suggests that Thrombate III is safer and more effective than FFP when none of these characteristics have been compared in an adequately and well-controlled manner.

Misleading Safety Claims

The sell sheet is misleading because it suggests that Thrombate III is safer than has been determined by substantial evidence or substantial clinical experience. There are significant safety risks involved with the use of Thrombate III for hemostasis, particularly involving the interaction of Thrombate III and heparin. Heparin is commonly used in high risk situations for which Thrombate III is indicated. The Warnings section of the PI states that the anticoagulant effect of heparin is enhanced by concurrent treatment with Thrombate III in patients with hereditary AT deficiency. Thus, in order to avoid bleeding, reduced dosage of heparin is recommended during treatment with Thrombate III. Concomitant use of heparin and Thrombate III requires careful monitoring. Therefore, the following statement, on page 2 of the sell sheet, is misleading: "Thrombate III reduces the risk of thrombotic events without increasing the risk of bleeding."

Recommendations

We suggest that you remove the following claims in the sell sheet because they imply that the use of Thrombate III is required in the management of homeostasis in patients with hereditary AT deficiency when, in fact, management of homeostasis in all such patients does not require the use of Thrombate III. Thrombate III is indicated only in high risk situations, such as surgical or obstetrical procedures and for the treatment of thromboembolism.

  • "Necessary"
  • "Thrombate III…the Necessary Therapy"
  • "Thrombate III … Necessary Therapy in Hereditary Antithrombin (AT) Deficiency
    "A necessity in every hospital"

In addition, we recommend that you do not use the term "treatment" in the phrase "the only treatment approved by the FDA" because it implies that FDA has approved a particular practice of medicine.

Conclusion and Requested Action

For the reasons discussed above, your professional sell sheet misbrands Thrombate III ( Antithrombin III, Human) within the meaning of section 502(a) of the Act (21 U.S.C. §352(a); Cf. 21 CFR 202.1(e)(6)(i) and (ii)), because it makes misleading superiority and safety claims.

We request that Talecris immediately cease the dissemination of this violative promotional material for Thrombate III, as well as promotional materials 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 Thrombate III, 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, 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 Thrombate III 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.

Sincerely,

/Robert A. Sausville/

Robert A. Sausville
Director, Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research

Enclosure