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Innovative Design and Analysis for PK/PD Biosimilar Bridging Studies with Multiple References

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Abstract

When there are multiple reference products, (e.g., EU-approved product and US-licensed product), a pharmacokinetic/pharmacodynamic (PK/PD) bridging study is often conducted in order to bridge the clinical data from the original region (e.g., Europe) to the new region (e.g., USA) in support of the biosimilar regulatory submission in the new region. The purpose is to avoid duplicated clinical trials for clinical similarity between a proposed biosimilar product and the reference product in the new region provided that there is no ethnic concern in the two regions. In this article, some innovative statistical designs for PK/PD biosimilar bridging studies are proposed. Statistical model and methods under the proposed statistical designs are studied. Power analysis for sample size requirement based on Schuirmann’s two one-sided tests procedure is also derived and compared to pairwise testing using simulation.

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Data Availability

The R simulation generated output data are available online at https://github.com/ywangaz/bridging-study-biosimlar.

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Acknowledgements

We would like to acknowledge the support from Peking University, Center for Food and Drug Inspection China, Peking Union Medical College Hospital, and Duke University School of Medicine.

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Authors and Affiliations

  1. Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health, National Clinical Research Center for Mental Disorders, Peking University, Beijing, China

    Fuyu Song & Hongqiang Sun

  2. Center for Food and Drug Inspection, National Medical Products Administration, Beijing, China

    Fuyu Song

  3. Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing, China

    Xin Zheng

  4. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, 2424 Erwin Road, Durham, NC, USA

    Yujia Wang & Shein-Chung Chow

Authors
  1. Fuyu Song
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  2. Xin Zheng
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  4. Shein-Chung Chow
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Contributions

Conceptualization: Song F., Zheng X., Chow S.C., and Sun H. Methodology: Song F., Zheng X., and Chow S.C. Simulation and analysis: Wang Y. Validation: Chow S.C. and Wang Y. Writing (original draft preparation): Song F., Chow S.C., and Wang Y. Writing (review and editing): Chow S.C. Visualization: Wang Y. Supervision: Sun H. and Chow S.C.

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Correspondence to Yujia Wang or Hongqiang Sun.

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The authors declare no competing interests.

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Supplementary Information

The R simulation code and generated output data files are available online at https://github.com/ywangaz/bridging-study-biosimlar

Below is the link to the electronic supplementary material.

Supplementary file1 (R 11 KB)

Supplementary file2 (RMD 2 KB)

Supplementary file3 (CSV 7 KB)

Supplementary file4 (CSV 3 KB)

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Song, F., Zheng, X., Wang, Y. et al. Innovative Design and Analysis for PK/PD Biosimilar Bridging Studies with Multiple References. AAPS J 24, 3 (2022). https://doi.org/10.1208/s12248-021-00658-x

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