ZLB Behring LLC, King of Prussia, PA, Feb. 3 (CBER).

Center for Biologics' OCBQ reviewed a Professional Sales Aid and an American Hospital Formulary Service Fact Sheet for ZLB Behring's product Rhophylac [RhIg (anti-D)] and found the marketing items to be misleading because the sales aid made unsubstantiated superiority claims and the fact sheet promoted an unapproved, potentially unsafe, use of Rhophylac.

The PI for Rhophylac states that it is recommended only for specific pregnancy and obstetrical conditions, including suppression of Rh isoimmunization in non-sensitized RhIg(D)-negative (D-negative) women. The criteria for an Rh-incompatible pregnancy requires administration of Rhophylac at 28 to 30 weeks of gestation and within 72 hours after delivery if the mother is RhIg(D)-negative; the mother is carrying a child whose father is either RhIg(D)-positive or RhIg(D) unknown; or, if the baby is either RhIg(D)-positive or RhIg(D) unknown, and the mother has not been previously sensitized to the RhIg(D) factor.

The PI states the product may also be used for rhesus prophylaxis in case of obstetric complications, such as, miscarriage, abortion, threatened abortion, ectopic pregnancy or hydatidiform mole, or transplacental hemorrhage resulting from antepartum hemorrhage; and for rhesus prophylaxis in case of invasive procedures during pregnancy, such as, amniocentesis, chorionic biopsy or obstetric manipulative procedures.

Additionally, the PI for Rhophylac indicates it is recommended for the suppression of Rh isoimmunization in RhIg(D)-negative individuals transfused with RhIg (D)-positive red blood cells (RBCs) or blood components containing RhIg (D)-positive RBCs. The PI also includes detailed risk information including contraindications, warnings, precautions and AEs.

Neither the sales aid nor the fact sheet gave detailed risk information. Furthermore, Center for Biologics took issue with unsubstantiated superiority, safety and purity claims made in the sales aid comparing Rhophylac with another anti-D product, Johnson& Johnson's Rhogam.

The sales aid made such claims as: "There's nothing wrong with RhoGAM ... There's just more right with Rhophylac"; "[Rhophylac] is the only liquid anti-D with a guaranteed 300 ug dose and rapid clearance of at least 15 mL of RBC"; "[Rhophylac] is the only liquid anti-D that utilizes two dedicated viral safety steps"; and, "[Rhophylac] is the only liquid anti-D with IgA levels below detection of 5 ug/mL ... Pure enough to be administered IV ..."

In addition, CBER pointed out that ZLB Behring had modified the fact sheet to include a use that is not approved for Rhophylac. Although the fact sheet was originally prepared by the American Society of Health-System Pharmacists, Inc., the new, customized fact sheet states that it was modified by ZLB Behring and that "all answers to the questions were prepared and furnished by ZLB Behring." In particular, the agency took issue with a statement made on page 2 of the fact sheet, under item number 7 of the "Pharmacologic Classification" section, the provided off-label uses of the product, including that it could be used to treat idiopathic thrombocytopenic purpura. F-M, O-L Use; Doc. 13745W