Recombinant FVIII Products (Turoctocog Alfa and Turoctocog Alfa Pegol) Stable Up to 40°C.

PURPOSE: The stability under high-temperature conditions of factor VIII (FVIII) concentrates for replacement therapy is of critical importance to patients, particularly those who reside in, or travel to, regions with high ambient temperatures. Concerns about product stability may limit or prevent access to treatment for patients and may limit their ability to live a close-to-normal life. This study evaluated the effect of hot and humid storage conditions on the long-term stability of the recombinant FVIII products, turoctocog alfa and turoctocog alfa pegol. METHODS: Turoctocog alfa samples were assessed for stability at 30°C for 9 months or 40°C for 3 months following storage at 5°C for 21 or 27 months, respectively, while turoctocog alfa pegol samples were assessed at 30°C for 12 months or 40°C for 3 months following storage at 5°C for 18 or 27 months, respectively. In addition, turoctocog alfa and turoctocog alfa pegol dry powders were evaluated for stability at 5°C/ambient humidity (AH) for 30 months, 30°C/75% relative humidity (RH) for 12 months and 40°C/75% RH for 6 months. Both studies utilized a range of product strengths. Key stability assessments included oxidized forms, potency, water content and high molecular weight protein (HMWP). RESULTS: Both turoctocog alfa and turoctocog alfa pegol remained stable following storage at 40°C/75% RH for 3 months, and at single temperatures (5°C/AH, 30 and 40°C/75% RH), without any major increase in HMWP or any impairment of potency or water content. CONCLUSION: Turoctocog alfa and turoctocog alfa pegol offer stability at 40°C for up to 3 months without jeopardizing the quality of each product. These stability characteristics may offer patients flexibility with product storage and daily use.

Stability of Turoctocog Alfa, a Recombinant Factor VIII Product, during Continuous Infusion In Vitro.

Objective Turoctocog alfa is a recombinant factor VIII (rFVIII) for the prevention and treatment of bleeding in patients with hemophilia 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. Materials and Methods The study was performed at 30°C ( ± 2°C). A CI system with pump speed set at either 0.6 or 1.5 mL/h was used to evaluate the stability of three turoctocog alfa strengths (500, 1,000, and 3,000 IU), equating to doses of 1.1 to 16.1 IU/h per kilogram of body weight. The following parameters were evaluated at selected time points between 0 and 24 hours: appearance of solution, clarity, pH, potency, purity, content, total high molecular weight proteins (HMWPs), and oxidized rFVIII. Results The mean potency of turoctocog alfa was maintained within the predefined acceptance criteria during CI for both pump speeds with all three strengths at 6, 12, or 24 hours (500 IU: ≥484 IU/vial; 1,000 IU: ≥1,014 IU/vial; and 3,000 IU: ≥3,029 IU/vial). Furthermore, the appearance of solution, clarity, pH, purity, content of turoctocog alfa, total HMWP, and oxidized forms were also within the predefined limits, and comparable to the reference samples (time = 0 hours) for the pump speeds and product strengths assessed. Conclusion Physical and chemical stability of turoctocog alfa was maintained during CI over 24 hours. There was only minor degradation or changes in any of the parameters tested. Potency was within the prespecified acceptance limits throughout 24 hours of infusion. These findings confirm the suitability of turoctocog alfa for CI.

The Effect of Fluctuating Temperature on the Stability of Turoctocog Alfa for Hemophilia A.

BACKGROUND AND OBJECTIVE: Factor VIII (FVIII) is indicated for the prevention or treatment of bleeding in patients with hemophilia A. FVIII product stability under high and fluctuating temperatures is important, particularly for patients who reside in, or travel to, regions with high ambient temperatures, as they may remove their product from the refrigerator and return it, unused, multiple times. We evaluated the effect of variable temperature storage conditions, including up to 40 °C, on the stability of the recombinant FVIII product, turoctocog alfa. METHODS: Turoctocog alfa dry powder stability was assessed when moved between storage conditions of 5 °C (ambient humidity) and 40 °C (75% relative humidity) multiple times over a 2-month period, followed by long-term storage at 40 °C for 3 months and 5 °C for 1 month. Three product strengths (250, 1500, and 3000 IU), including the lowest and highest doses, were evaluated. Stability assessments included potency, purity, oxidized forms, high molecular weight protein (HMWP), and water content. RESULTS: Overall, the three doses of turoctocog alfa tested remained stable under varying temperature conditions, without any potency or purity impairment, nor were any major increases in oxidized forms, HMWP, or water content observed. All results were within shelf-life specification limits. CONCLUSION: The results demonstrated that turoctocog alfa can be subjected to variable storage conditions, including cycling between 5 °C and ≤ 40 °C, and subsequent storage for 3 months up to 40 °C, without loss of stability. This suggests that turoctocog alfa may offer greater product storage flexibility for patients in everyday practice, with a potential reduction in wastage.

Room-temperature-stable recombinant activated coagulation factor VII recombinant: chemical and microbiologic stability over 24 hours during continuous in vitro infusion.

rFVIIa-25C is a recombinant coagulation factor VIIa (rFVIIa) formulated to remain stable at room temperature (up to 25°C) for up to 2 hours. The bolus injection of rFVIIa-25C has been reported to be bioequivalent to that of rFVIIa. With alternative administration by continuous infusion (50 µg/kg/h) for surgical hemostatic coverage in hemophilia patients with inhibitors, rFVIIa has been reported to be stable. This research letter presents data from an in vitro study of the activity and chemical stability (rFVIIa content, clot activity, and degradation products), physical stability, and microbiologic stability of rFVIIa-25C administered as a continuous infusion. The findings suggest that rFVIIa-25C remained biochemically stable and aseptic during 24-hour continuous infusion in vitro at 19.3°C to 20.7°C, with no clinically significant changes in clot activity, solution constituents, or concentrations.