The AAPS Journal

, 21:105 | Cite as

Retrospective Analysis of Bioanalytical Method Validation Approaches in Biosimilar Biological Product Development

  • O. N. Obianom
  • Theingi M. ThwayEmail author
  • S. J. Schrieber
  • O. O. Okusanya
  • Y. M. Wang
  • S. M. Huang
  • I. Zineh
Research Article


Development and validation of a bioanalytical method for biosimilar biological product development (BPD) can be challenging. It requires the development of a bioanalytical method that reliably and accurately measures both proposed biosimilar and reference products in a biological matrix. This survey summarizes the current state of bioanalysis in BPD. Bioanalytical data from 28 biosimilar biologic license applications submitted to U.S. Food and Drug Administration (FDA) up to December 2018 were analyzed. The aim of the analysis was to provide (i) a summary of the bioanalytical landscape for BPD, (ii) a cumulative review of bioanalytical method validation approaches to aid in understanding how a specific method was selected, and (iii) a summary of data regarding bioanalytical bias differences between products. Results show diversity of the bioanalytical approaches used, as well as the observed differences in bioanalytical bias. Our findings highlight the need for understanding the critical aspects of BPD bioanalysis and clarifying BPD bioanalytical best practices, which could help ensure consistent method validation approaches in the BPD community.


Biosimilar bioanalysis Therapeutic biologics 351(k) BLAs Bioanalytical method comparability 



authentic reference product


%difference from accuracy


biologic license application


biosimilar biological development program


contract research organization


coefficient of variation


enzyme-linked immunosorbent assay


ligand binding assay


Meso Scale Discovery




quality control


proposed biosimilar product


US reference product


World Health Organization



The authors thank Joanne Berger, FDA Library, and Daniel Sloper, NCTR, for manuscript editing assistance and Dr. Elimika Pfu Fletcher, Office of Clinical Pharmacology, FDA for her critical review of the manuscript.


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • O. N. Obianom
    • 1
  • Theingi M. Thway
    • 1
    Email author
  • S. J. Schrieber
    • 2
  • O. O. Okusanya
    • 1
  • Y. M. Wang
    • 1
  • S. M. Huang
    • 1
  • I. Zineh
    • 1
  1. 1.Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research,U.S. Food and Drug AdministrationSilver SpringUSA
  2. 2.Office of New Drugs, Center for Drug Evaluation and ResearchU.S. Food and Drug AdministrationSilver SpringUSA

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