"The U.S. Food and Drug Administration yesterday approved Rixubis [Coagulation Factor IX (Recombinant)] for use in people with hemophilia B who are 16 years of age and older. Rixubis is indicated for the control and prevention of bleeding episodes"...
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The Factor VIII correctional activity of Autoplex® T (anti-inhibitor coagulant complex, heat treated) , Anti-Inhibitor Coagulant Complex, Heat Treated, is thought to be, in part, related to the Factor Xa content of the product. It is additionally hypothesized that the elevated Factor VII-VIIa content of this product is also a contributing factor in the in vivo reestablishment of normal hemostasis by way of Factor X activation in conjunction with tissue factor, phospholipid and ionic calcium.
Control of thrombin formation is regulated by (1) the presence of antithrombin III and other serine protease inhibitors which neutralize Factors IXa and Xa, (2) the short biological half-lives of Factors VII and VIIa and (3) the presence of the circulating Factor VIII inhibitor which additionally controls overactivation of the intrinsic coagulation system.
A retrospective study conducted with patients receiving unheated Autoplex®, Anti-Inhibitor Coagulant Complex, supports the effectiveness of the purification process in reducing viral burden in the product. In the study, none of the patients who received that product exclusively seroconverted for HIV antibodies, while 56% of those patients who received other treatment modalities seroconverted during the three year study.1
Autoplex® T (anti-inhibitor coagulant complex, heat treated) is manufactured by the modified Cohn-Oncley cold ethanol fractionation process which includes a series of cold-ethanol precipitation, centrifugation and/or filtration of human plasma. Autoplex® T (anti-inhibitor coagulant complex, heat treated) solution is then lyophilized and heat treated at 60°C ± 1°C for 144 to 153 hours. These processes accomplish both purification and virus inactivation.
In vitro studies demonstrate that the manufacturing process for Autoplex® T, Anti-Inhibitor Coagulant Complex, Heat Treated, provides for significant viral reduction. These studies, summarized in Table 1, demonstrate viral clearance during the Autoplex® T (anti-inhibitor coagulant complex, heat treated) manufacturing process using Sindbis Virus (SIN) and Bovine Viral Diarrhea virus (BVD) as lipid-enveloped models for RNA viruses such as hepatitis C virus; human immunodeficiency virus, type 1 (HIV-1), a relevant blood borne pathogen; and a herpes virus, pseudorabies virus (PRV), as a model for lipid enveloped DNA viruses. Additionally, studies using three non-enveloped viruses were performed: encephalomyocarditis virus, a model for non-lipid enveloped viruses such as hepatitis A virus; hepatitis A virus, a relevant RNA virus; and porcine parvovirus (PPV), a model for non-lipid enveloped DNA viruses including human B19 parvovirus. The cumulative reduction factors obtained from a combination of these steps indicate that the Autoplex® T (anti-inhibitor coagulant complex, heat treated) manufacturing process is capable of eliminating/inactivating a wide range of relevant and model viruses exhibiting diverse physicochemical properties.
Table 1: In Vitro Virus Clearance During the Autoplex®
T Manufacturing Process
|Process Step Evaluated||Lipid-Enveloped Viruses||Non-Lipid Enveloped Viruses|
|Processing of Cryo-Poor Plasma to Fraction I+II+III Centrifugate||2.6||1.2||4.6||5.8‡||2.1||1.9||1.4|
|Processing of Fraction I+II+IIICentrifugate to Fraction IV1 Precipitate||N/A||0.5*||0.5*||8.2||N/A||0.7*||0.2*|
|Fraction IV1 Supernatant Precipitated with CalciumPhosphate||1.4||N/A||N/A||N/A||1.5||N/A||N/A|
|aPCC Precipitated with 5% PEG||1.4||N/A||N/A||N/A||1.5||N/A||N/A|
|Lyophilization and Heat Treatment Cycle||5.0||4.3||3.4||6.1||7.1||2.3||N/A|
|Cumulative Log Reduction factors Log10||10.4||5.5||8.0||14.3||12.2||4.2||1.4|
|* Since reduction factor of ≤ 1.0 is within
the variability limit of the assay, these values are not included in the
cumulative reduction factor calculation.
‡This value is not included in cumulative because 8.2 claimed in the next step has the same virus inactivation mechanism.
N/A Steps not evaluated.
1. Gazengel C, Larrieu MJ: Lack of seroconversion for LAV/HTLV-III in patients exclusively given unheated activated prothrombin complex prepared with ethanol step. Lancet 2:1189, 1985
Last reviewed on RxList: 1/13/2009
This monograph has been modified to include the generic and brand name in many instances.
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