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Determination of Similarity Margin in Comparative Clinical Studies to Support the Development of Biosimilar Products of Neupogen® (Filgrastim, Granulocyte Colony-Stimulating Factor [G-CSF])

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Abstract

To demonstrate a biological product is biosimilar to a reference product, the applicant needs to show that the product is highly similar and has no clinically meaningful differences. Comparative clinical studies are often conducted to support the conclusion of no clinically meaningful differences, as a part of totality of evidence. The FDA has published several guidance documents to facilitate the development of biosimilar products. While the guidance documents define the role and objective of comparative clinical studies, they do not provide details about the determination of the similarity margin. In this paper, we illustrate a similarity margin derivation for a surrogate endpoint in comparative clinical studies conducted to assess whether clinically meaningful differences exist between Neupogen® (Filgrastim, granulocyte colony-stimulating factor) and products proposed to be biosimilar to Neupogen®.

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Acknowledgements

The authors thank Dr Leah Christl, Dr Shein-Chung Chow, and three reviewers for their very helpful comments and suggestions.

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Authors and Affiliations

  1. Division of Biometrics IV, OB/OTS/CDER/FDA, Silver Spring, MD, 20993-0002, USA

    Lei Nie, Rajeshwari Sridhara & Thomas E. Gwise

  2. Division of Hematology Products, OHOP/OCE/FDA, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA

    Donna Przepiorka & Albert Deisseroth

Authors
  1. Lei Nie
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  2. Donna Przepiorka
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  3. Albert Deisseroth
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  4. Rajeshwari Sridhara
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  5. Thomas E. Gwise
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Corresponding author

Correspondence to Lei Nie.

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No external funding was used in the preparation of this manuscript.

Conflict of interest

Authors L. Nie, D. Przepiorka, A. Deisseroth, R. Sridhara, and T. E. Gwise declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Disclaimer: This article reflects the views of the authors and should not be construed to represent the views or policies of the FDA.

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Nie, L., Przepiorka, D., Deisseroth, A. et al. Determination of Similarity Margin in Comparative Clinical Studies to Support the Development of Biosimilar Products of Neupogen® (Filgrastim, Granulocyte Colony-Stimulating Factor [G-CSF]). BioDrugs 32, 325–330 (2018). https://doi.org/10.1007/s40259-018-0288-z

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  • DOI: https://doi.org/10.1007/s40259-018-0288-z

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