Primary manuscript

Stability of turoctocog alfa, a recombinant factor VIII product, during continuous infusion in vitro

Kawasugi K, Pollard D, Nøhr AM, Normann Rasmussen DK, Taaftegaard Jensen J, Takeyama M

Kawasugi K, Pollard D, Nøhr AM, Rasmussen DKN, Jensen JT, Takeyama M. Stability of turoctocog alfa, a recombinant factor VIII product, during continuous infusion in vitro. Haemophilia. 2019;25(Suppl 1):48. P025.

Date of Publication

Introduction: Turoctocog alfa (NovoEight®) is a recombinant factor VIII (rFVIII) product used for prophylaxis against and treatment of bleeding in patients with haemophilia A, including those undergoing surgery and invasive medical procedures. This in vitro study evaluated the physical and chemical stability of turoctocog alfa during continuous infusion (CI) over 24 hours at 30 ° C. Methods: The study was performed at 30 ° C (± 2 ° C). Three strengths of turoctocog alfa (500, 1000 and 3000 IU) were reconstituted to 4.3 ml in NaCl solution, according to the manufacturer's recommendations. The CI system comprised a B Braun Perfusor® Space automatic infusion pump, a BD™ Plastipak™ syringe and an Original-Perfusor ® Line infusion tube, with pump speed set at either 0.6 or 1.5 ml/h. Turoctocog alfa concentrations equating to doses of 1.1-16.1 IU/h/kg body weight were assessed. The following parameters were evaluated at selected time points between 0-24 hours: appearance of solution, clarity, pH, potency, content, total high molecular weight proteins (HMWPs), purity, and oxidised rFVIII. FVIII activity was measured using both the one-stage clotting and chromogenic assays. Results: The potency of turoctocog alfa was maintained within the acceptance criteria during CI for both pump speeds with all three strengths at 6, 12 or 24 hours (500 IU: ≥476 IU/vial; 1000 IU: ≥1005 IU/vial; 3000 IU: ≥2980 IU/vial). Purity was within the acceptance criteria at 6, 12 or 24 hours for both pump speeds (500 IU: ≥94.4%; 1000 IU: ≥94.6%; 3000 IU: ≥92.4%). There tended to be a small increase in oxidised forms (500 IU: ≤3.1%; 1000 IU: ≤2.7%; 3000 IU: ≤3.1%), but these were all within acceptance criteria limits. Minor increases in total HMWP (all within the acceptance criteria), was observed with all three strengths (highest value: 2.8% at 24 hours for 3000 IU). Content, appearance, clarity and pH all remained within acceptance criteria. Discussion/Conclusion: Chemical and physical stability of turoctocog alfa was maintained during CI over 24 hours. There was no degradation or change in any of the parameters tested. Potency was within the pre-specified shelf-life specification range throughout 24 hours of infusion. These findings confirm the suitability of turoctocog alfa for CI for clinical use, such as in the surgical setting.

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