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PURPOSES Liquid protein-based biopharmaceutical formulations have been reported to form aggregation and protein sub-visible particles (SbVPs) during dropping (Randolph et al., J Pharm Sci 2015, 104, 602). However, effects of secondary package on liquid biopharmaceutical formulation stability during dropping are overlooked and have not been reported so far. This study reports the first real-world evaluation on effects of secondary package on liquid biopharmaceutical formulation stability during dropping, using two monoclonal antibodies (mAb-1 and mAb-2) and one fusion protein (FP-1) as model biopharmaceuticals. METHODS The potential protective effects of secondary package and formulation composition on liquid biopharmaceutical formulations during dropping were evaluated with micro-flow imaging (MFI) and dynamic light scattering (DLS). RESULTS The dropping-induced degradation could be detected with the two sensitive particle analyzing techniques MFI and DLS. Formulation compositions have dramatic impact on biopharmaceutical stability during dropping. Surprisingly, unlike the primary packages that have been reported to impact liquid biopharmaceutical stability, the secondary packaging system as described in our current preliminary design has little or no protective effect during dropping. CONCLUSIONS Our study is the first real-world data showing that the secondary package system has little to no effect on the liquid biopharmaceutical formulation quality during dropping. On the contrary, the stability of liquid biopharmaceutical formulations during dropping is more relevant to formulation compositions and primary packages.