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In-Use Physicochemical and Biological Stability of the Trastuzumab Biosimilar CT-P6 Upon Preparation for Intravenous Infusion

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Abstract

Background

CT-P6 is a biosimilar of trastuzumab, a monoclonal antibody targeting human epidermal growth factor 2 (HER2), that is used in the treatment of breast and gastric cancers.

Objective

The aim of this study was to evaluate the in-use physicochemical and biological stability of CT-P6 following preparation for intravenous (IV) infusion.

Methods

One batch of CT-P6 within the final month of its 48-month shelf life was used to simulate sub-optimal administration conditions. CT-P6 dilutions of 0.4, 1.0, and 4.0 mg/mL, representative of actual use scenarios, were prepared in 0.9% saline solution in either polypropylene (PP) or polyvinylchloride (PVC) infusion bags. Following refrigeration at 2–8 °C for 1 month, samples were incubated at room temperature for 24 h. Physicochemical and biological stability were evaluated according to presence of sub-visible particles, pH, proportion of molecular weight variants, oxidation level of methionine residues 107, 255/256 and 432/433, and binding affinity to the Fc neonatal receptor and HER2.

Results

Analyses of CT-P6 preparations at all concentrations tested and in both PP and PVC infusion bags revealed no changes in sub-visible particles, pH, molecular weight variants, oxidation, or potency after 1 month at 2–8 °C followed by exposure to room temperature for 24 h.

Conclusion

These analyses demonstrate the extended stability, after refrigerated storage for 1 month followed by 24-h exposure to room temperature, of CT-P6 under the dilution conditions required for IV infusion. This stability was sustained for all dilution factors and both infusion bag materials tested.

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Acknowledgements

Medical writing support (including development of a first and subsequent drafts in consultation with the authors, assembling tables and figures, collating author comments, copyediting, fact checking, and referencing) was provided by Emma Prest, PhD at Aspire Scientific (Bollington, UK) and was funded by Celltrion Healthcare Co., Ltd. (Incheon, Republic of Korea). Drafts were reviewed by Sang-Wook Yoon, PhD and Dasom Choi at Celltrion Healthcare Co., Ltd.

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Authors and Affiliations

  1. R&D Division, Biotechnology Research Institute, Celltrion Inc., Incheon, Korea

    Su Jung Kim, Joon Won Lee, Hye Young Kang, So Young Kim, Yeon Kyeong Shin, Kwang Woo Kim, Jun Seok Oh, Ki Jung Lim & Ji Young Kim

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  1. Su Jung Kim
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  2. Joon Won Lee
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  3. Hye Young Kang
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  4. So Young Kim
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  6. Kwang Woo Kim
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  7. Jun Seok Oh
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  8. Ki Jung Lim
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  9. Ji Young Kim
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Corresponding author

Correspondence to Su Jung Kim.

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Funding

This study was sponsored by Celltrion, Inc.

Conflict of interest

All authors are employees of Celltrion, Inc. The authors have no other conflicts of interest related to this work.

Author contributions

SJK and JWL were involved in the conception and design of this study. SJK, JWL, HYK, SYK, YKS, KWK, JSO, KJL, and JYK were involved in the acquisition, analysis, and/or interpretation of the data. SJK, JWL, HYK, SYK, YKS, KWK, JSO, KJL, and JYK developed the manuscript and approved the final version for submission.

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Kim, S.J., Lee, J.W., Kang, H.Y. et al. In-Use Physicochemical and Biological Stability of the Trastuzumab Biosimilar CT-P6 Upon Preparation for Intravenous Infusion. BioDrugs 32, 619–625 (2018). https://doi.org/10.1007/s40259-018-0314-1

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  • DOI: https://doi.org/10.1007/s40259-018-0314-1

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