VIA FACSIMILE AND CERTIFIED MAIL
RETURN RECEIPT REQUESTED
February 3, 2006
Paul Hartmann, R.Ph.
Senior Director, Regulatory Affairs
ZLB Behring LLC
P.O Box 61501
King of Prussia, PA 19406-0901
Re: BLA STNs # 125070/85 and 98
Dear Mr. Hartmann:
The Office of Compliance and Biologics Quality (OCBQ) in the Food and Drug Administration's Center for Biologics Evaluation and Research (CBER) has reviewed a Professional Sales Aid (IO# RHP 51) (Sales Aid) and an American Hospital Formulary Service (AHFS) Fact Sheet (IO# RHP47) (Fact Sheet) for Rhophylac submitted by ZLB Behring LLC (ZLB Behring) under cover of Form FDA 2253. These materials result in the misbranding of Rhophylac under section 502(a) and (f)(1) of the Federal Food, Drug, and Cosmetic Act (the Act), (21 U.S.C. § 352(a) and (f)(1)) because the Sales Aid makes unsubstantiated superiority claims (Cf. 21 CFR 202.1(e)(6)(ii)), and because the Fact Sheet promotes an unapproved use (Cf. 21 CFR 202.1(e)(6)(i)). By promoting unsubstantiated comparative claims and by promoting an unapproved use, you are potentially encouraging the unsafe use of Rhophylac.
The Indications and Usage section of the FDA-approved labeling (PI) for Rhophylac states that it is recommended for the following pregnancy and obstetrical conditions:
For the suppression of Rh isoimmunization in non-sensitized Rho(D)-negative (D-negative) women. The criteria for an Rh-incompatible pregnancy requiring administration of Rhophylac at 28 to 30 weeks of gestation and within 72 hours after delivery are:
- The mother must be Rho(D)-negative.
- The mother is carrying a child whose father is either Rho(D)-positive or Rho(D) unknown.
- The baby is either Rho(D)-positive or Rho(D) unknown, and the mother must not be previously sensitized to the Rho(D) factor.
- For Rhesus prophylaxis in case of obstetric complications, e.g., miscarriage, abortion, threatened abortion, ectopic pregnancy or hydatidiform mole, transplacental hemorrhage resulting from antepartum hemorrhage.
- For Rhesus prophylaxis in case of invasive procedures during pregnancy, e.g., amniocentesis, chorionic biopsy or obstetric manipulative procedures, e.g., external version, or abdominal trauma.
The Indications and Usage section of the PI for Rhophylac states that it is also recommended for the following incompatible transfusion indication:
The PI also includes detailed risk information including contraindications, warnings, precautions, and adverse reactions.
Unsubstantiated Superiority Claims
The Sales Aid contains a comparison of two different anti-D products, Rhophylac and Rhogam. The following claims are presented as a large headline:
Only liquid anti-D with a guaranteed 300 ug dose and rapid clearance of at least 15 mL of RBC .
Only liquid anti-D that utilizes 2 dedicated viral safety steps .
Only liquid anti-D with IgA levels below detection of 5 ug/mL . Pure enough to be administered IV. "
Drug comparisons that represent or suggest that a product is safer or more effective than another product are misleading if not supported by data consisting of substantial evidence, or substantial clinical experience. FDA is unaware of any comparative studies of these two products, or any clinical experience, to support the presentation of such superiority claims. If you have data consisting of substantial evidence or substantial clinical experience to support your claims, please submit the data, within ten (10) days of the date of this letter, to CBER for review. In the absence of such data, you should immediately discontinue any further use of these claims in all promotional materials.
Promotion of an Unapproved Use
You have modified the Fact Sheet to include a use that is not approved for Rhophylac. While we acknowledge that the Fact Sheet was originally prepared by the American Society of Health-System Pharmacists, Inc., the Fact Sheet states that it was modified by ZLB Behring and that all answers to the questions were prepared and furnished by ZLB Behring.
Specifically, on page 2 of the Fact Sheet, under item number 7 of the "Pharmacologic Classification" section, you provide the following information:
ZLB Behring supplied the following answer:
This Fact Sheet was then disseminated by ZLB Behring to health-care practitioners. You should immediately discontinue any further use of this question and response in all promotional materials.
Conclusion and Requested Action
Your Fact Sheet and Sales Aid misbrand Rhophylac within the meaning of section 502(a) and (f)(1) of the Act (21 U.S.C. §352(a) and (f)(1))) because the Sales Aid makes unsubstantiated superiority claims (Cf. 21 CFR 202.1(e)(6)(ii)), and because the Fact Sheet promotes an unapproved use (Cf. 21 CFR 202.1(e)(6)(i)). .
We request that ZLB Behring immediately cease the dissemination of the violative promotional materials for Rhophylac 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 Rhophylac such as the Fact Sheet and Sales Aid described above, and explaining your plan for discontinuing use of such materials. Please direct your response to Maryann Gallagher 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 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 Rhophylac 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 promotional materials.
----- signature -----
Robert A. Sausville
Director, Division of Case Management
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
A - American Hospital Formulary Service (AHFS) Fact Sheet (RHP47)
B - Professional Sales Aid for Rhophylac (IO# RHP 51)