Accelerated Production of Biopharmaceuticals via Microwave-Assisted Freeze-Drying (MFD)

Abstract

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.

Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations

“…However, the relationship between microwave-assisted freeze-drying processes and protein concentrations remains unclear. Recent studies have demonstrated that increasing the solute concentrations of stabilizers, such as sucrose and trehalose, results in enhanced dielectric heating [ 13 , 17 ]. To further investigate the effect of protein concentration in microwave-assisted drying processes, we gradually substituted sucrose with mAb (F1–F4, Table 1 ) and applied drying process P1 ( Table 2 ).…”

“…Numerous reviews have been provided on the rational design of robust and optimized freeze-drying processes [ 4 , 5 , 6 , 7 ], as well as ideas for speeding up the typically lengthy process [ 8 , 9 , 10 , 11 ]. More recently, microwave-assisted freeze-drying (MFD) has gained attention due to its potential for significant time savings while maintaining the product quality of probiotics [ 12 ], vaccines, and proteins [ 13 , 14 ] and, more specifically, monoclonal antibodies (mAbs) [ 15 , 16 , 17 ]. While heat transfer in conventional freeze-drying (CFD) is primarily limited to convection, with some conduction and radiation, microwaves directly interact with the dipolar molecules of the formulation [ 18 ].…”

“…We recently introduced a new MFD setup that overcomes the drawbacks of previous machines, as it enables in-chamber freezing and stoppering [ 17 ]. This setup combines the advantages of a conventional lyophilizer, which was designed with good manufacturing practice (GMP) processes in mind, with microwave radiation.…”

“…It employs flat, solid microwave modules that can be flexibly incorporated into the process. For details on the new setup, readers are referred to [ 17 ]. Additionally, we assessed mAb stability following MFD and found it to be comparable to mAb stability following CFD.…”

“…Residual water great affects heat transfer because of the much higher effective loss factor of water compared to ice [19]. We hypothesized that microwaves excite the unfrozen water, and this causes the glass transition temperature T g Pharmaceutics 2023, 15, 2783 2 of 16 to increase during drying [17]. As a result, drying processes become more robust and can be conducted very fast without impairing cake appearance.…”