FDA Approves Revised Alphanate® Labeling to Include Reduced Infectivity of an Experimental Model Agent for vCJD

BARCELONA, Spain, March 4, 2011 /PRNewswire/ -- Grifols, a global healthcare company and biopharmaceutical manufacturer based in Barcelona, Spain today announced that it received approval from the US Food and Drug Administration (FDA) for revised labeling for Alphanate® Antihemophilic Factor/von Willebrand Factor Complex (Human) indicating that certain manufacturing steps have been shown to reduce the infectivity of a experimental TSE agent that is a model for variant Creutzfeldt Jakob Disease (vCJD).  The labeling revisions stem from extensive Grifols research into the capacity for various manufacturing steps to eliminate a TSE experimental model agent.  Data supporting the revised labeling was the result of work done in Grifols' research and development laboratories and was published in 2009 in the peer-reviewed journal Haemophilia, the official journal of the World Federation of Hemophilia (1).

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"This is the result of years of research, significant investment, and most importantly the dedication of many Grifols scientists," said Juan Ignacio Jorquera, Ph.D., the Director of Research and Development at Grifols.  "The potential of vCJD transmission by blood or blood products has been an area of substantial inquiry among global health authorities for more than a decade and we are proud to reach this important milestone," continued Dr. Jorquera.  Alphanate® is the first plasma-derived blood clotting factor product to receive FDA-approved revised labeling that recognizes that manufacturing steps adopted by the company "provide reasonable assurance that low levels of CJD/vCJD agent infectivity, if present in the starting material, would be removed."  

"Because of our history, the bleeding disorders community has a responsibility to be informed and vigilant about the safety of the medicines we take," said Val Bias, CEO of the National Hemophilia Foundation. "It is encouraging to know that Grifols shares this responsibility with the community and is actively engaged in demonstrating the safety of their products," continued Mr. Bias.

In 2007 Alphanate® became the first dual virus inactivated (heat treatment and solvent detergent) and affinity chromatography purified clotting factor complex approved for the treatment of von Willebrand Disease (VWD) and hemophilia A. Some of the same manufacturing processes that are proven effective at eliminating viruses also have demonstrated the ability to remove the CJD/vCJD experimental agent. Specific manufacturing steps with infectivity reduction capacity include polyethylene glycol precipitation, affinity chromatography and saline precipitation.

Grifols' research used two different experimental agent preparations as well as Western blot and bioassay detection methods.  Validated scale models of the production steps for both Alphanate® and Grifols' Fanhdi® (FVIII/VWF complex product marketed outside the United States) were used in the studies.  The combined effect of the production steps provided an imputed reduction capacity of 8 log₁₀ of the experimental CJD/vCJD agent.  

(1) DIEZ, J. M., CABALLERO, S., BELDA, F. J., OTEGUI, M., GAJARDO, R. and JORQUERA, J. I.  Elimination capacity of a TSE-model agent in the manufacturing process of Alphanate®/Fanhdi®, a human factor VIII/VWF complex concentrate. Haemophilia 2009, 15: (6), 1249-1257.

About Alphanate®

Antihemophilic Factor/von Willebrand Factor Complex (Human), Alphanate®, is indicated for the prevention and control of bleeding in patients with Factor VIII deficiency due to hemophilia A.  Alphanate®, is also indicated for surgical and/or invasive procedures in adult and pediatric patients with von Willebrand Disease, except Type III undergoing major surgery, in whom desmopressin (DDAVP®) is either ineffective or contraindicated.  Antihemophilic factor potency (Factor VIII:C activity) is expressed in International Units (IU) on the product label.  Additionally, each vial of Alphanate® also contains VWF:RCo activity in IU for the treatment of VWD.

Alphanate® is contraindicated in patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis, to the product or its components.  Anaphylaxis and severe hypersensitivity reactions are possible.  Development of activity-neutralizing antibodies has been detected in patients receiving FVIII containing products.  Development of alloantibodies to VWF in Type 3 VWD patients has been occasionally reported in the literature.   Thromboembolic events may be associated with AHF/VWF Complex (Human) in VWD patients, especially in the setting of known risk factors.  Intravascular hemolysis may be associated with infusion of massive doses of AHF/VWF Complex (Human).  Rapid administration (>10mL/minute) of a FVIII concentrate may result in vasomotor reactions.  The most frequent adverse events reported with Alphanate® in > 5% of patients are respiratory distress, pruritus, rash, urticaria, face edema, paresthesia, pain, fever, chills, joint pain and fatigue.

Because Alphanate is made from pooled human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob Disease (CJD) agent. Stringent procedures designed to reduce the risk of adventitious  agent transmission have been employed in the manufacture of this product, from the screening of plasma donors and the collection and testing of plasma, through the application of viral elimination/reduction steps such as solvent detergent and heat treatment in the manufacturing process. Despite these measures, such products can still potentially transmit disease; therefore, the risk of infectious agents cannot be totally eliminated.

About Grifols

Grifols is a global healthcare company founded in 1940 in Barcelona, Spain. Today Grifols' products and services are provided in more than 90 countries around the world. Grifols specializes in the production of plasma therapies to treat a variety of life-threatening diseases and conditions. Grifols operates 80 plasma donor centers throughout the US and has manufacturing facilities located in Barcelona, Spain and Los Angeles, California. For more information about Grifols, please visit www.grifols.com.

SOURCE Grifols