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

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Presentation on theme: "WFH Bangkok 2004 Octanine F – Factor IX at its Peak Very High Purity Factor IX Virus Inactivation and Elimination Haemophilia B Treatment and Prophylaxis."— Presentation transcript:

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

2 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

3 WFH Bangkok 2004 Octanine F – Indications Prophylaxis and treatment of bleeding in all forms of Haemophilia B Dosage

4 WFH Bangkok 2004 Octanine F Dosage Haemorrhagic Event FIX level Required Duration Minor haemorrhage Joint bleeds 20 – 40 %> 1 day Major haemorrhage Muscle bleeds Dental extraction 30 – 60 % days or until wound healing Life-threatening haemorrhage Major surgery 60 – 100 % Until wound healing then 7 days at 30 – 60 % On Demand: 1 IU of Octanine F per kg BW increases factor IX levels by 1.3 % Prophylaxis: 20 – 30 IU of Octanine F / kg BW x twice weekly

5 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

6 WFH Bangkok 2004 Cryoprecipitate supernatant plasma, pooled at a scale of ~ 3000 L is subjected to the first ion exchange capture step for the factors of the prothrombin complex, factors II, VII, IX and X Ultrafiltration serves to remove low molecular weight contaminants The second ion exchange chromatography provides selective enrichment of factor IX The first virus inactivation is solvent/detergent (S/D) to inactivate lipid-coated viruses The affinity chromatography step achieves very high purification of factor IX The second step of virus elimination and a further purification is carried out using nanofiltration, with a Viresolve 70 filter in TFF mode. The filter pore size is chosen to permit the passage of factor IX through the membrane, while larger particles (viruses, protein impurities) are retained Octanine F Manufacturing Process

7 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 log 10 Other process steps provide additional safety *CPMP/BWP/268/95, CPMP/BWP/269/95 rev 3., 2001

8 WFH Bangkok 2004 Octanine F – Virus Validation Studies Enveloped VirusesNon Enveloped Viruses Virus Genome HIV-1 Human Immuno- deficiency Virus RNA SBV Sindbis Virus RNA HSV-1 Herpes Simplex Virus DNA HAV Hepatitis A Virus RNA REO Reovirus-3 RNA PPV Porcine Parvovirus DNA StepVirus Reduction (log 10 ) S/D Treatment > 6.7> 7.4> 6.2 Nanofiltration> 5.0> 7.3> > Other process steps Total Reduction > 11.7> 14.7> >

9 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

10 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)

11 WFH Bangkok 2004 Octanine F – Pharmacokinetics ParameterOctanine F Predecessor F IX Preparation Half-Life (t ½, h) 29.1 ± ± 8.4 Recovery (IU/dl per IU/kg) 1.3 ± ± 0.3 Area Under the Curve (AUC, %.h.IU -1.kg) 37.7 ± ± 13.7 Mean Residence Time (MRT, h) 40.0 ± ± 8.4 Clearance (CL, ml.h -1.kg) 2.9 ± ± 0.7

12 WFH Bangkok 2004 Octanine F – Pharmacokinetics Octanine F pharmacokinetics were evaluated in 12 patients in a cross-over study with a predecessor preparation (Octanine F process without nanofiltration) Octanine F was applied at a dose of 75 IU per kg BW The pharmacokinetics were followed up to 72 h The similarity of all pharmacokinetic parameters allowed the two preparations to be judged as equivalent

13 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

14 WFH Bangkok 2004 Octanine F – Surgery PatientAge (y)Procedure Octanine F Total Dose (IU) Treatment duration/ CI duration (d/d) JB56Cataract: lens implantation19,5005/4 KS26Pseudotumour (tibia, l) removal39,00014/13 ZR63Inguinial hernia46,0008/6 AJ40Caldwell-Luc operation54,00015/7 RP40Hip and knee joint replacement65,00012/11 AJ40 Hip joint replacement, pseudo- Tumour (tibia, l) removal 53,00013/10 AL62 Pyelolithotomy, pseudo- Tumour (tibia, l) removal 57,00016/0 KS54Tooth extraction5,0001/0 SS41Tooth extraction4,0001/0 AJ39Tooth extraction4,0001/0

15 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 2505 ml Octanine F 5005 ml Octanine F ml


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