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Secondary Packages cannot Protect Liquid Biopharmaceutical Formulations from Dropping-Induced Degradation

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Abstract

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.

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Abbreviations

CHO:

Chinese Hamster Ovary

DLS:

Dynamic light scattering

FDA:

U.S. Food and Drug Administration

FP:

Fusion protein

mAb:

Monoclonal antibody

MFI:

Micro-flow imaging

MVSS:

MFI View System Suite

MW:

Molecular weight

PU:

Polyurethane

SbVP:

Sub-visible particle

SP:

Secondary package

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ACKNOWLEDGMENTS AND DISCLOSURES

We greatly appreciate the Ministry of Science and Technology of China (Grant No. 2018ZX09J18107–002) and the National Natural Science Foundation of China (Grant No. 81741144) for financial support. We would also like to extend our gratitude to Ms. Haihong Hu at Zhejiang University for lab management.

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Authors and Affiliations

  1. Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    Wei-Jie Fang, Jia-Wei Liu & Han Gao

  2. Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou, 310016, China

    Wei-Jie Fang, Jia-Wei Liu & Han Gao

  3. Institute for Composites Science Innovation, School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310027, China

    Yan-Chen Qian

  4. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    Jian-Qing Gao

  5. Zhejiang Bioray Biopharmaceutical Co., Taizhou, 317000, China

    Haibin Wang

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  1. Wei-Jie Fang
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Correspondence to Wei-Jie Fang.

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Fang, WJ., Liu, JW., Gao, H. et al. Secondary Packages cannot Protect Liquid Biopharmaceutical Formulations from Dropping-Induced Degradation. Pharm Res 38, 1397–1404 (2021). https://doi.org/10.1007/s11095-021-03073-1

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  • DOI: https://doi.org/10.1007/s11095-021-03073-1

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