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WFH Bangkok 2004
Octanate – Factor VIII with the Safety Factor VWF
High Purity Plasma-Derived Factor VIII
Double Virus Inactivated
Haemophilia A Treatment and Prophylaxis
WFH Bangkok 2004
Octanate at a Glance
Physiological factor VIII
Naturally stabilised with VWF Highly purified Non denatured
Extensive clinical use
Safe Effective Well-tolerated
State-of-the-art virus safety
High quality starting plasma Double virus inactivation:Solvent / Detergent (S/D) treatment Short duration dry heating, 100 °C, 30 min
Convenient handling
Small injection volume Easy documentation
WFH Bangkok 2004
Octanate Manufacturing Process
Cryoprecipitate
Resuspension in ethanol-heparin
Aluminium hydroxide addition
Adsorption and precipitation
S/D virus inactivation
Ion exchange chromatography
Ultrafiltration, diafiltration
Sterile filtration, filling
Lyophilisation, vial closure
Terminal dry heating, 100 °C, 30 min
OCTANATE
WFH Bangkok 2004
Octanate – Viral Safety: Conclusion
Octanate fulfils all current requirements for virus safety set out by regulatory bodies, such as the Committee for Proprietary Medicinal Products*
Two effective steps against lipid enveloped viruses
One effective step against non enveloped viruses
A combination of methods based on different principles of action
Inactivation procedures with a high safety margin
Rapid virus inactivation
Robustness in the event of process variations
Validation of each step with a wide variety of viruses
An individual step efficacy equivalent to 4 log10
Other process steps provide additional safety
*CPMP/BWP/268/95, 1996. CPMP/BWP/269/95 rev 3., 2001
WFH Bangkok 2004
Importance of von Willebrand Factor
Biosynthesis of factor VIII VWF imparts correct factor VIII structure and secretion
Stabilisation of factor VIII Protects against
unwanted activation and degradation
Transport of factor VIII Directs factor VIII to
the site of injury
Octanate – Physiologically Stabilised with VWF
WFH Bangkok 2004
Octanate – Pharmacokinetics
Parameter Octanate
(Study 1, n = 10)
Octanate
(Study 2, n = 14)
Half-Life
(t ½ , h)14.3 ± 4.01 12.6 ± 3.03
Recovery
(IU/dl per IU/kg)2.4 ± 0.36 2.4 ± 0.25
Area Under the Curve (AUC, %.h.IU-1.kg)
45.5 ± 17.20 33.4 ± 8.50
Mean Residence Time
(MRT, h)19.6 ± 6.05 16.6 ± 3.73
Clearance
(CL, ml.h-1.kg)2.6 ± 1.21 3.2 ± 0.88
WFH Bangkok 2004
Octanate – Clinical Efficacy
95.3 % of All Bleeding Episodes Resolved Within 3 Days
0%
25%
50%
75%
100%
Total (N=1,096) AVE-401 (N=167) AVE-402 (N=374) AVE-406 (N=213) AVE-407 (N=342)
Re
so
lve
d W
ith
in (
%)
1 day
2 day
3 day
4 day
5 day
6 day
7 day
> 5 days
No. Bleeds 1096 (Total) 167 (Study 1) 374 (Study 2) 213 (Study 3) 342 (Study 4)
WFH Bangkok 2004
Octanate at a Glance – In Daily Clinical Use
Clinical safety and efficacy
No inhibitors No virus transmissions Very well tolerated Very good efficacy Successful use in surgery, and in continuous infusion
Convenient handling Small injection volume Easy documentation Pull-off labels Dissolves rapidly Complete application set
Presentation
Storage and shelf-life
24 months shelf-life at + 4 °C to + 8 °C. Do not freeze. Protect from light
Package Size (IU) Injection Volume
Octanate 250 5 ml
Octanate 500 10 ml
Octanate 1000 10 ml