(Factor IX Complex) for Intravenous Administration
Profilnine®, Factor IX Complex, is a solvent/detergent treated, nanofiltered, sterile,
lyophilized concentrate of coagulation factors IX, II, X, and low levels of
factor VII. The factor II content is not more than (NMT) 150 units* per 100
factor IX units, the factor X content is NMT 100 units per 100 factor IX units,
and the factor VII content is NMT 35 units per 100 factor IX units. Profilnine
does not contain heparin and contains no preservatives. Profilnine contains
few, if any, activated factors based on results from the non-activated partial
thromboplastin time (NAPTT) test1,2.
Profilnine is intended for intravenous administration
only. Each vial is a single-dose container and is labeled with the factor IX
potency expressed in International Units.
Profilnine is prepared from pooled human plasma and
purified by diethylaminoethyl (DEAE) cellulose adsorption. The risk of
transmission of infective agents by Profilnine has been substantially reduced
by donor selection procedures and virus screening of individual donations and
plasma pools by serological and nucleic acid testing. In addition, virus
elimination steps such as nanofiltration3 and solvent/detergent
(tri-n-butyl phosphate) treatment4 have been incorporated into the
Profilnine manufacturing process. Additional removal of some viruses occurs
during the DEAE cellulose product purification step.
The ability of the manufacturing process to eliminate
virus from Profilnine was evaluated in the laboratory by intentionally adding
virus to product just prior to the elimination step and monitoring virus removal.
Table 1 shows the amounts of virus that can be removed by solvent/detergent
treatment, nanofiltration, and purification by DEAE chromatography when
vesicular stomatitis virus (VSV), human immunodeficiency virus-1 and 2 (HIV-1,
HIV-2), parvovirus, West Nile virus (WNV), bovine viral diarrhea virus (BVDV),
hepatitis A virus (HAV), and pseudorabies virus (PRV) were evaluated in these virus
spiking studies. The results indicate that the solvent/detergent treatment step
inactivates enveloped viruses and the nanofiltration step removes both
enveloped and non-enveloped viruses.
Table 1: Virus Reduction
||Virus Reduction (log10)
|1st DEAE Chromatography
||Process Step Solvent- Detergent
|| ≥ 5.3
||Robust enveloped viruses
|| ≥ 4.9
|| ≥ 12.2
|| ≥ 6.2
|| ≥ 6.0
|| ≥ 6.6
|| ≥ 4.9
|| ≥ 6.1
|| ≥ 5.8
|| ≥ 5.3
|* Porcine, NT=Not tested, Env=Enveloped
* Unit refers to International Unit in the labeling of
1. Menache, D., Roberts, H.R. Summary report and
recommendations of the task force members and consultants. Thromb Diath
Haemorrh 33:645-647, 1975.
2. Kingdon, H.S., Lundblad, R.L., Veltkamp, J.J.,
Aronson, D.L. Potentially thrombogenic materials in Factor IX Concentrates. Thromb
Diath Haemorrh 33:617- 631, 1975.
3. Burnouf T, Radosevich M. Nanofiltration of
plasma-derived biopharmaceutical products. Haemophilia : the official journal
of the World Federation of Hemophilia. 2003;9:24-37.
4. DichtelmÃ¼ller HO, Biesert L, Fabbrizzi F, Gajardo R,
Gröner A, von Hoegen I, Jorquera JI, Kempf C, Kreil TR, Pifat D, Osheroff W,
Poelsler G. Robustness of solvent/detergent treatment of plasma derivatives: a
data collection from Plasma Protein Therapeutics Association member companies. Transfusion