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Liquid biopharmaceuticals including monoclonal antibodies (mAbs) have been widely acknowledged to undergo various stresses during shipping/handling and long-term storage. Several mechanical stresses including shaking during shipping has been widely known to cause protein aggregation and sub-visible particle (SbVP) formation in liquid biopharmaceutical formulations. However, shaking-induced degradation of freeze-dried (FD) biopharmaceuticals has seldomly been reported in the literature and therefore this type of stress is widely overlooked in industry due to their presumed high stability, especially when the formulations and freeze-drying processes are fully optimized. In this Lessons Learned article, we report an interesting phenomenon in which the optimized FD biopharmaceutical formulations of three typical mAbs showed much degradation and SbVP formation under shaking stress compared with their liquid counterparts. This is a striking deviation to the notion that mAbs are generally more stable in the FD formulations than in the liquid ones. Therefore, shaking stress experiment should be considered a critical stress condition for early-stage selection of liquid versus FD mAb formulations. [ABSTRACT FROM AUTHOR]

Previously our laboratory first reported that dropping of freeze-dried monoclonal antibody (mAb) formulations could cause protein degradation and aggregation (J Pharm Sci, 2021, 1625). In this manuscript, we evaluated effects of secondary package on stability of several freeze-dried biopharmaceutical formulations during dropping. The degradation of mAb-Y during dropping with different secondary packages was determined by the sensitive particle analyzing techniques micro-flow imaging (MFI) and dynamic light scattering (DLS). Electron paramagnetic resonance (EPR) was used to detect free radicals after repeated dropping in different secondary packages. The amount of free radicals and SbVPs was correlated to the sample temperature as well as the secondary package during dropping. Our observations suggest that secondary packaging has significant effect on freeze-dried biopharmaceutical stability during dropping and therefore should be thoroughly screened and optimized to assure high product quality even for the presumed highly stable freeze-dried biopharmaceuticals. [ABSTRACT FROM AUTHOR]