Application of the parallel line assay to assessment of biosimilar products based on binary endpoints


  • Jr-Rung Lin,

    1. Clinical Informatics and Medical Statistics Research Center and Graduate Institute of Clinical Medicine, Chang Gung University, Tao-Yuan, Taiwan
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    • §

      Equal contributions

  • Shein-Chung Chow,

    1. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, U.S.A.
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    • Equal contributions

  • Chih-Hsi Chang,

    1. Center for Disease Control, Department of Health, Taipei, Taiwan
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  • Ya-Ching Lin,

    1. Statistics Education Center, National Taiwan University, Taipei, Taiwan
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  • Jen-pei Liu

    Corresponding author
    1. Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
    • Division of Biometry, Department of Agronomy and Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
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  • The views expressed in this article are personal opinions of the authors and may not necessarily represent the position of the National Taiwan University, the National Health Research Institutes, the Chang Gung University, Taiwan, and the Duke University School of Medicine, U.S.A.

Jen-pei Liu, PhD, Professor, Division of Biometry, Department of Agronomy, National Taiwan University, Taipei, Taiwan.



Biological drug products are therapeutic moieties manufactured by a living system or organisms. These are important life-saving drug products for patients with unmet medical needs. Because of expensive cost, only a few patients have access to life-saving biological products. Most of the early biological products will lose their patent in the next few years. This provides the opportunity for generic versions of the biological products, referred to as biosimilar drug products. The US Biologic Price Competition and Innovation Act passed in 2009 and the draft guidance issued in 2012 provide an approval pathway for biological products shown to be biosimilar to, or interchangeable with, a Food and Drug Administration-licensed reference biological product. Hence, cost reduction and affordability of the biosimilar products to the average patients may become possible. However, the complexity and heterogeneity of the molecular structures, complicated manufacturing processes, different analytical methods, and possibility of severe immunogenicity reactions make evaluation of equivalence between the biosimilar products and their corresponding reference product a great challenge for statisticians and regulatory agencies. To accommodate the stepwise approach and totality of evidence, we propose to apply a parallel assay to evaluate the extrapolation of the similarity in product characteristics such as doses or pharmacokinetic responses to the similarity in binary efficacy endpoints. We also report the results of simulation studies to evaluate the performance, in terms of size and power, of our proposed methods. We present numerical examples to illustrate the suggested procedures. Copyright © 2012 John Wiley & Sons, Ltd.