WFH Bangkok 2004 Octanine F – Factor IX at its Peak Very High Purity Factor IX Virus Inactivation and Elimination Haemophilia B Treatment and Prophylaxis.

WFH Bangkok 2004

Octanine F – Factor IX at its Peak

Very High Purity Factor IX

Virus Inactivation and Elimination

Haemophilia B Treatment and Prophylaxis

WFH Bangkok 2004

Octanine F Features at a Glance

Gently, highly purified

Factor IX enriched 10,000fold over plasma Specific activity 150 to 200 IU/mg Non denatured, fully active

Safe in clinical use

Effective and well-tolerated Non thrombogenic Non immunogenic

Virus inactivation and elimination

High quality starting plasma Solvent / Detergent (S/D) treatment Nanofiltration

WFH Bangkok 2004

Octanine F – Indications

Prophylaxis and treatment of bleeding in all forms of Haemophilia B

Dosage

WFH Bangkok 2004

Octanine F Manufacturing Process

Cryoprecipitate supernatant plasma

Ion exchange capture

Ultrafiltration/Diafiltration

Ion exchange chromatography

S/D virus inactivation

Affinity chromatography

Virus removal: Nanofiltration

Sterile filtration, filling

Lyophilisation

Quality Control and Batch Release

OCTANINE F

WFH Bangkok 2004

Octanine F – Viral Safety: Conclusion

Octanine F 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/removal 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

Octanine F – Purified, Non Denatured Factor IX

Gentle purification steps avoid

undesired Factor IX activation

Octanine F: Non denatured factor IX

Octanine F: Non activated factor IX

A: Molecular weight markers

B: Activated factor IX (Sigma)

C: Non activated factor IX, Octanine F

WFH Bangkok 2004

Octanine F – Purity

Octanine F is a high purity preparation of plasma-derived factor IX

Octanine F specific activity is in the range of 150 to 200 IU/mg of protein

Non detectable: Activated factor IX, as well as factors II, VII and X and their activated derivatives (IIa, VIIa, Xa)

WFH Bangkok 2004

Octanine F – Pharmacokinetics

Parameter Octanine F Predecessor F IX

Preparation

Half-Life

(t ½ , h)29.1 ± 5.2 31.7 ± 8.4

Recovery

(IU/dl per IU/kg)1.3 ± 0.5 1.3 ± 0.3

Area Under the Curve (AUC, %.h.IU-1.kg)

37.7 ± 13.0 43.3 ± 13.7

Mean Residence Time

(MRT, h)40.0 ± 7.3 43.6 ± 8.4

Clearance

(CL, ml.h-1.kg)2.9 ± 0.9 2.5 ± 0.7

WFH Bangkok 2004

Octanine – Clinical Experience

Octanine F at a mean dosage of 22.5 IU per kg BW for one or two treatment days was enough to ensure haemostasis in 93 % of cases in the treatment of acute bleeding

Octanine F efficacy was rated as “excellent” or “good” in 98 % of all cases

Octanine F has been used successfully in surgery

WFH Bangkok 2004

Octanine F at a Glance – In Daily Clinical Use

Good clinical experience

Excellent general safety Effective in prophylaxis Effective in bleeding control Effective in surgery Well-tolerated

Convenient handling

Small injection volume Easy documentation Pull-off labels Dissolves rapidly

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

Octanine F 250 5 ml

Octanine F 500 5 ml

Octanine F 1000 10 ml