, Volume 32, Issue 4, pp 325–330 | Cite as

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

  • Lei NieEmail author
  • Donna Przepiorka
  • Albert Deisseroth
  • Rajeshwari Sridhara
  • Thomas E. Gwise
Current Opinion


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®.



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

Compliance with Ethical Standards


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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Copyright information

© This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection 2018

Authors and Affiliations

  • Lei Nie
    • 1
    Email author
  • Donna Przepiorka
    • 2
  • Albert Deisseroth
    • 2
  • Rajeshwari Sridhara
    • 1
  • Thomas E. Gwise
    • 1
  1. 1.Division of Biometrics IVOB/OTS/CDER/FDASilver SpringUSA
  2. 2.Division of Hematology ProductsOHOP/OCE/FDASilver SpringUSA

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