wfh bangkok 2004 nanotiv – factor ix concentrate plasma-derived, very high purity factor ix...
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WFH Bangkok 2004
Nanotiv – Factor IX Concentrate
Plasma-derived, Very High Purity Factor IX Concentrate
WFH Bangkok 2004
Nanotiv – Factor IX Concentrate
Nanotiv is a highly pure factor IX concentrate derived from carefully selected donors and extensively tested plasma
The Nanotiv manufacturing process is designed to fulfil the highest modern requirements for virus safety by combining two reliable and validated methods of virus elimination
The Nanotiv manufacturing process is gentle, in order to preserve biological function of the factor IX, reduce the risk of thrombogenicity and lead to good clinical tolerance
WFH Bangkok 2004
Nanotiv – Rigorously Controlled Plasma
Carefully selected donors Controlled donation centres Extensive donation testing
– HBsAg – Anti-HCV – Anti-HIV – ALT – Syphilis
PCR tests on – Mini pools and – Production pools
Inventory holding
WFH Bangkok 2004
Nanotiv Manufacturing Process
Cryoprecipitate supernatant plasma
Anion exchange chromatography
S/D Virus inactivation
Affinity chromatography
Cation exchange chromatography
Virus removal: Nanofiltration
Diafiltration
Ultrafiltration
Sterile filtration
Lyophilisation
NANOTIV
WFH Bangkok 2004
Nanotiv – Nanofiltration
WFH Bangkok 2004
Nanotiv – Viral Safety: Conclusion
Nanotiv factor IX 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
*CPMP/BWP/268/95, 1996. CPMP/BWP/269/95 rev 3., 2001
WFH Bangkok 2004
Nanotiv Purity
Nanotiv is among the purest factor IX preparations available
Prothrombin complex factors are removed to trace amounts
The high purity of Nanotiv is the prerequisite for its excellent clinical tolerability and efficacy
WFH Bangkok 2004
High purity factor IX preparations, like Nanotiv are almost devoid of other vitamin K-dependent factors, as well as phospholipids
They are less likely to be thrombogenic, compared with products of low purity
Even at very high dose (200 IU/kg BW), Nanotiv still does not have an elevated thrombogenic effect
Nanotiv – In Vivo Thrombogenicity
WFH Bangkok 2004
Nanotiv – Clinical Efficacy, Pharmacokinetics
0
0.1
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0.3
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0.5
0.6
0 12 24 36 48 60 72 84
Nanotiv
MAB-purifiedcompetitor
Mean plasma concentration (IU/ml) vs. time (h), n = 12
WFH Bangkok 2004
Nanotiv – Clinical Efficacy
Half-life (t½, hours) 22.6
In vivo recovery (%) 58.3
Incremental recovery (IU/dl per IU/kg) 1.2
Clearance (ml x kg x h-1) 4.84
Pharmacokinetic Parameters
WFH Bangkok 2004
Nanotiv – 6 Months Follow Up Study
1009690
80
0
20
40
60
80
100
120
1 2 3 >4Number of injections
Per
cen
t o
f b
leed
s
Most bleeding episodes were managed using a single dose of (mean) 29 IU/kg BW
Number of injections per bleed vs. Cumulative % of bleeds managed
% o
f b
leed
s
WFH Bangkok 2004
Nanotiv – Clinical Efficacy Summary
In comparative pharmacokinetic studies, Nanotiv half-life and recovery values were within the normal range
After 6 months, the same cohort of patients showed similar values for half-life and recovery as at the beginning
Nanotiv gave no inhibitors
Most bleeding episodes were managed using a single dose of Nanotiv with a mean of 29 IU/kg BW
Nanotiv was well-tolerated
WFH Bangkok 2004
Nanotiv – Clinical Efficacy in Surgery
Nanotiv was well-tolerated in surgery At high bolus doses and in continuous infusion The haemostatic effect always rated as good or excellent No signs of thrombosis or pulmonary embolism observed No adverse events observed No inhibitors detected 14 days after conclusion of
continuous infusion
WFH Bangkok 2004
Nanotiv – Convenience: All You Need
Water for Injections Alcohol swab x 3 Transfer needle Filter needle Syringe Infusion line (Butterfly) Gauze Plaster
WFH Bangkok 2004
Nanotiv at a Glance – Key Features
Highly purified factor IX
Triple chromatography process Specific activity ~ 200 IU/mg Gentle purification Non denatured
Heparin-free formulation
Reduced risk of thrombocytopenia Minimal interference with diagnostic tests
Complementary virus safety concept
High quality starting plasma Double virus elimination procedures Solvent / Detergent (S/D) treatment Nanofiltration Chromatographic steps provide additional safety
WFH Bangkok 2004
Nanotiv at a Glance – In Daily Clinical Use
Extensive clinical experience
Excellent general safety proven over more than 10 y Effective Well-tolerated
Convenient handling
Small injection volume Easy documentation Pull-off labels Dissolves rapidly
Presentation
Storage and shelf-life
36 months shelf-life at + 4 °C to + 8 °C
1 month storage at elevated temperature up to 25 °C
Package Size (IU) Injection Volume
Nanotiv 500 5 ml
Nanotiv 1000 10 ml