Biopharmaceuticals are often lyophilized to improve their storage stability. Controlling ice nucleation during the freezing step of the lyophilization process is desired to increase homogeneity of product properties across a drug product batch and shorten the primary drying time. The present communication summarizes the process optimization of the freezing process when using vacuum-induced surface freezing to control ice nucleation, in particular for amorphous samples. We characterized freeze-dried samples for solid state properties, and compared these to uncontrolled nucleated samples using bovine serum albumin (BSA) as a model protein. Freezing parameters were optimized to obtain complete nucleation, adequate cake resistance during the subsequent lyophilization cycle, and elegant cakes. We highlight the challenges associated with vacuum-induced surface freezing and propose optimized freezing parameters to control ice nucleation, enabling manufacturing of amorphous samples.

中文翻译：

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冻干过程中控制冰成核：真空诱导表面冷冻的工艺优化

通常将生物药物冻干以改善其储存稳定性。需要在冻干过程的冷冻步骤中控制冰的成核作用，以增加整个药品批次中产品特性的均质性并缩短初级干燥时间。本交流总结了在使用真空诱导的表面冻结来控制冰核化时，特别是对于无定形样品的冻结过程的过程优化。我们表征了冻干样品的固态特性，并使用牛血清白蛋白（BSA）作为模型蛋白将这些样品与不受控制的有核样品进行了比较。优化冷冻参数以获得完全成核，在随后的冻干循环期间足够的抗滤饼性和精美的滤饼。