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

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Abstract

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.

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Abbreviations

ARP:

authentic reference product

Bias:

%difference from accuracy

BLA:

biologic license application

BPD:

biosimilar biological development program

CRO:

contract research organization

CV:

coefficient of variation

ELISA:

enzyme-linked immunosorbent assay

LBA:

ligand binding assay

MSD:

Meso Scale Discovery

PK:

pharmacokinetic

QC:

quality control

PBP:

proposed biosimilar product

USRP:

US reference product

WHO:

World Health Organization

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Acknowledgments

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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Authors and Affiliations

  1. Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research,, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA

    O. N. Obianom, Theingi M. Thway, O. O. Okusanya, Y. M. Wang, S. M. Huang & I. Zineh

  2. Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 20993, USA

    S. J. Schrieber

Authors
  1. O. N. Obianom
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  2. Theingi M. Thway
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  3. S. J. Schrieber
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  4. O. O. Okusanya
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  5. Y. M. Wang
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  6. S. M. Huang
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  7. I. Zineh
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Correspondence to Theingi M. Thway.

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Study Highlights

• Among twenty-eight 351(k) BLA submissions received up to December 2018, ELISA remains the most frequently used platform in BPD, likely due to the technology’s simplicity. Since most reagents were commercially sourced in these submissions, it may be beneficial for bioanalytical laboratories to qualify and manage the life cycles of critical reagents and include critical reagent information sufficiently in method validation reports.

• Our survey indicated the diversity in conducting the bioanalytical comparability assessment among these submissions and the evidence corroborating the rationale for choosing the single bioanalytical method and the product was not evident. The bioanalytical bias differences between the products were larger than 10% in many cases.

• Evaluating the impact of bioanalytical bias difference on the outcome of PK similarity studies may be important.

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Obianom, O.N., Thway, T.M., Schrieber, S.J. et al. Retrospective Analysis of Bioanalytical Method Validation Approaches in Biosimilar Biological Product Development. AAPS J 21, 105 (2019). https://doi.org/10.1208/s12248-019-0376-0

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  • DOI: https://doi.org/10.1208/s12248-019-0376-0

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