Kogenate FS Antihemophilic Factor (Recombinant) is a
coagulation factor VIII produced by recombinant DNA technology. It is produced
by Baby Hamster Kidney (BHK) cells into which the human factor VIII gene has
been introduced.8 The cell culture medium contains
Human Plasma Protein Solution (HPPS) and recombinant insulin, but does not
contain any proteins derived from animal sources. Kogenate FS is a purified
glycoprotein consisting of multiple peptides including an 80 kD and various
extensions of the 90 kD subunit. It has the same biological activity as factor
VIII derived from human plasma. No human or animal proteins, such as albumin,
are added during the purification and formulation processes of Kogenate FS.
The purification process includes a solvent/detergent virus
inactivation step in addition to the use of the purification methods of ion
exchange chromatography, monoclonal antibody immunoaffinity chromatography,
along with other chromatographic steps designed to purify recombinant factor
VIII and remove contaminating substances.
Additionally, the manufacturing process was investigated for
its capacity to decrease the infectivity of an experimental agent of
transmissible spongiform encephalopathy (TSE), considered as a model for the
vCJD and CJD agents.9-21 Several of the individual production and
raw material preparation steps in the Kogenate FS manufacturing process have
been shown to decrease TSE infectivity of that experimental model agent. TSE
reduction steps include the Fraction II+III separation step for HPPS (6.0
log10) and an anion exchange chromatography step (3.6 log10).
Kogenate FS is formulated with the following as stabilizers [see
Table 7] in the final container and is then lyophilized. The final product is a
sterile, nonpyrogenic, preservative-free, powder preparation for intravenous
(IV) injection. Intravenous administration of sucrose contained in Kogenate FS
will not affect blood glucose levels.
Table 7 : Stabilizers Contained in Kogenate FS Final
||250 IU, 500 IU, 1000IU
||2000 IU. 3000 IU
The following inactive ingredients/excipients are also
contained in the final product:
Table 8 : Inactive Ingredients/Excipients
||250 IU, 500 IU, 1000 IU
||2000 IU, 3000 IU
|Imidazole. tri-n-butyl phosphate. and copper
Each vial of Kogenate FS contains the labeled amount of
recombinant factor VIII in international units (IU). One IU, as defined by the
World Health Organization standard for blood coagulation factor VIII, human, is
approximately equal to the level of factor VIII activity found in 1 mL of fresh
pooled human plasma.
5. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker
MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint
disease in boys with severe hemophilia. N Engl J Med 2007;357(6):535-44.
8. Lawn RM, Vehar GA: The molecular genetics of hemophilia.
Sci Am 254(3):48–54, 1986.
9. Kimberlin RH, Walker CA: Characteristics of a short
incubation model of scrapie in the golden hamster. J Gen Virol 34(2):295-304,
10. Kimberlin RH, Walker CA: Evidence that the transmission
of one source of scrapie agent to hamsters involves separation of agent strains
from a mixture. J Gen Virol 39(3):487-96, 1978.
11. Kimberlin RH, Walker CA: Pathogenesis of scrapie (strain
263K) in hamsters infected intracerebrally, intraperitoneally or intraocularly.
J Gen Virol 67(2):255-63, 1986.
12. Prusiner SB, et al: Further purification and
characterization of scrapie prions. Biochemistry 21(26):6942-50, 1982.
13. Kascsak RJ, et al: Mouse polyclonal and monoclonal
antibody to scrapie-associated fibril proteins. J Virol 61(12):3688-93, 1987.
14. Rubenstein R, et al: Scrapie-infected spleens: analysis
of infectivity, scrapie-associated fibrils, and protease-resistant proteins. J
Infect Dis 164(1):29-35, 1991.
15. Taylor DM, Fernie K: Exposure to autoclaving or sodium
hydroxide extends the dose-response curve of the 263K strain of scrapie agent
in hamsters. J Gen Virol 77(4):811-13, 1996.
16. Stenland CJ, et al: Partitioning of human and sheep
forms of the pathogenic prion protein during the purification of therapeutic
proteins from human plasma. Transfusion 42(11):1497-500, 2002.
17. Lee DC, Miller JL, Petteway SR: Pathogen safety of
manufacturing processes for biological products: special emphasis on KOGENATE®
Bayer. Haemophilia 8(Suppl. 2):6-9, 2002.
18. Lee DC, Stenland CJ, Hartwell, RC, et al: Monitoring
plasma processing steps with a sensitive Western blot assay for the detection
of the prion protein. J Virol Methods 84(1):77-89, 2000.
19. Lee DC, Stenland CJ, Miller JL, et al: A direct
relationship between the partitioning of the pathogenic prion protein and
transmissible spongiform encephalopathy infectivity during the purification of
plasma proteins. Transfusion 41(4):449-55, 2001.
20. Cai K, Miller JL, Stenland CJ, et al: Solvent-dependent
precipitation of prion protein. Biochim Biophys Acta 1597(1):28-35, 2002.
21. Trejo SR, Hotta JA, Lebing W, et al: Evaluation of virus
and prion reduction in a new intravenous immunoglobulin manufacturing process.
Vox Sang 84(3):176-87, 2003.
What are the possible side effects of recombinant antihemophilic factor?
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; feeling light-headed, fainting; swelling of your face, lips, tongue, or throat.
Stop using recombinant antihemophilic factor and call your doctor at once if you have a serious side effect such as:
- chest pain;
- easy bruising, increased bleeding episodes; or
- bleeding from a wound or where the medicine was injected.
Less serious side effects may include:
- sore throat, cough, runny nose;
- fever or...
Read All Potential Side Effects and See Pictures of Kogenate FS »
What are the precautions when taking antihemophilic factor (recombinant) (Kogenate FS)?
Before using this medication, tell your doctor or pharmacist if you are allergic to any antihemophilic factor (factor VIII) products; or to animal proteins (e.g., mouse, hamster, cow); or if you have any other allergies. This product may contain inactive ingredients (such as natural rubber/latex found in the packaging of some brands), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
Before using this medication, tell your doctor or pharmacist your medical history.
Manufacturers of some brands of this medication recommend that you monitor your heartbeat during treatment. If your heart starts to beat faster, it is recommended that you give this medication more slowly or temporarily stop the infusion until your heart rate returns...
Read All Potential Precautions of Kogenate FS »
Last reviewed on RxList: 6/11/2012
This monograph has been modified to include the generic and brand name in many instances.