Härdter Nicole, Geidobler Raimund, Presser Ingo, Winter Gerhard
Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
Boehringer Ingelheim Pharma GmbH & Co. KG, Pharmaceutical Development Biologicals, 88397 Biberach an der Riß, Germany.
Pharmaceutics. 2023 Apr 27;15(5):1342. doi: 10.3390/pharmaceutics15051342.
Recently, attention has been drawn to microwave-assisted freeze-drying (MFD), as it drastically reduces the typically long drying times of biopharmaceuticals in conventional freeze-drying (CFD). Nevertheless, previously described prototype machines lack important attributes such as in-chamber freezing and stoppering, not allowing for the performance of representative vial freeze-drying processes. In this study, we present a new technical MFD setup, designed with GMP processes in mind. It is based on a standard lyophilizer equipped with flat semiconductor microwave modules. The idea was to enable the retrofitting of standard freeze-dryers with a microwave option, which would reduce the hurdles of implementation. We aimed to collect process data with respect to the speed, settings, and controllability of the MFD processes. Moreover, we studied the performance of six monoclonal antibody (mAb) formulations in terms of quality after drying and stability after storage for 6 months. We found drying processes to be drastically shortened and well controllable and observed no signs of plasma discharge. The characterization of the lyophilizates revealed an elegant cake appearance and remarkably good stability in the mAb after MFD. Furthermore, overall storage stability was good, even when residual moisture was increased due to high concentrations of glass-forming excipients. A direct comparison of stability data following MFD and CFD demonstrated similar stability profiles. We conclude that the new machine design is highly advantageous, enabling the fast-drying of excipient-dominated, low-concentrated mAb formulations in compliance with modern manufacturing technology.
最近，微波辅助冷冻干燥（MFD）受到了关注，因为它能大幅缩短生物制药在传统冷冻干燥（CFD）中通常较长的干燥时间。然而，先前描述的原型机缺乏诸如腔室冷冻和加塞等重要特性，无法进行具有代表性的小瓶冷冻干燥过程。在本研究中，我们提出了一种新的技术MFD装置，其设计考虑了GMP工艺。它基于一台配备平面半导体微波模块的标准冻干机。其理念是使标准冻干机能够通过微波选项进行改造，这将减少实施障碍。我们旨在收集关于MFD过程的速度、设置和可控性的过程数据。此外，我们研究了六种单克隆抗体（mAb）制剂在干燥后的质量和储存6个月后的稳定性。我们发现干燥过程大幅缩短且可控性良好，并且未观察到等离子体放电的迹象。冻干产品的表征显示出优雅的块状外观，并且MFD后的mAb具有非常好的稳定性。此外，即使由于高浓度的玻璃形成赋形剂导致残留水分增加，总体储存稳定性仍然良好。MFD和CFD之后的稳定性数据直接比较显示出相似的稳定性概况。我们得出结论，新的机器设计具有高度优势，能够根据现代制造技术对以赋形剂为主、低浓度的mAb制剂进行快速干燥。
