Pharmacology: Profilnine is a mixture of the vitamin K-dependent clotting factors IX, II, X and low levels of VII. The administration of factor IX complex, Profilnine, temporarily increases the plasma levels of factor IX, thus enabling a temporary correction of the factor deficiency.
A clinical study that evaluated twelve subjects with hemophilia B indicated that, following administration of Profilnine, the factor IX in vivo half-life was 24.68 ± 8.29 hours and recovery was 1.15 ± 0.16 units/dL per unit infused per kg body weight.
Administration of factor IX complex can result in higher than normal levels of factor II due to its significantly longer half-life.
The retrovirus known as Human Immunodeficiency Virus (HIV-1) has been identified as the causative agent of Acquired Immunodeficiency Syndrome (AIDS) and has been shown to be transmissible via blood or blood products. The solvent detergent process used in the manufacture of Profilnine has been shown to provide a very high level of virus kill without compromising protein structure and function. The susceptibility of human pathogenic viruses such as HIV-1, hepatitis B virus, hepatitis C virus and marker viruses such as Sindbis and Vesicular Stomatitis Virus (VSV) to inactivation by organic solvent detergent treatment has been discussed in the literature.
The solvent detergent process used in the manufacture of Profilnine was shown to inactivate greater than 12.2 logs of HIV-1 when the retrovirus was intentionally added to product samples under laboratory evaluation (as measured by virus antigen capture and reverse transcriptase assays). In addition, this process was shown to inactivate 6.0 logs of HIV-2 COMPLEX (as measured by reverse transcriptase assays) when the retrovirus was intentionally added to product samples.
In order to assess the ability of the solvent detergent process to inactivate other viruses such as hepatitis B and C virus, the inactivation of the model viruses, Sindbis virus and vesicular stomatitis virus (VSV), by solvent detergent treatment was studied. Prior to solvent detergent treatment, samples were inoculated with a titer of either Sindbis or VSV. The results demonstrated that a minimum of 5.3 logs of Sindbis and a minimum of 4.9 logs of VSV were removed after 180 minutes of incubation with solvent detergent (when compared to an untreated control). It should be noted that the incubation time in the actual Profilnine process is twice (360 minutes total) that used in the model virus studies.
The ability of the Profilnine process to eliminate virus, by physically partitioning virus from product, was evaluated at the DEAE chromatography step. Addition of Sindbis virus prior to factor IX complex adsorption by DEAE chromatography showed this step to eliminate 1.4 logs of added virus.
However, no treatment method has yet been shown capable of totally eliminating all potential infective virus in preparations of coagulation factor concentrates.