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.

中文翻译：

---

温度波动对甲型血友病阿尔法Turoctocog Al稳定性的影响。

背景和目的VIII因子（FVIII）用于预防或治疗A型血友病患者的出血。在高温和多变的温度下FVIII产品的稳定性很重要，特别是对于居住在或旅行到环境温度较高的地区的患者而言，因为他们可能会从冰箱中取出产品，并多次退还未使用的产品。我们评估了可变温度存储条件（包括最高40°C）对重组FVIII产品Turoctocog alfa稳定性的影响。方法在两个月内多次在5°C（环境湿度）和40°C（相对湿度75％）的存储条件之间移动，然后在40°C长期存储时，评估了Turoctocog alfa干粉的稳定性。 3个月，5°C 1个月。三种产品优势（250种，评估了最低剂量和最高剂量的1500和3000 IU）。稳定性评估包括效力，纯度，氧化形式，高分子量蛋白质（HMWP）和水含量。结果总体而言，在不同温度条件下测试的三剂Turoctocog alfa保持稳定，没有任何效力或纯度损害，也未观察到氧化形式，HMWP或水含量的任何重大增加。所有结果均在保质期内。结论结果表明，α-羟辛考酮可以在可变的储存条件下使用，包括在5°C至≤40°C之间循环，然后在40°C以下的温度下储存3个月，而不会失去稳定性。这表明turoctocog alfa可以为患者的日常操作提供更大的产品存储灵活性，