Bioanalysis Zone

Chapter 7: Case studies: challenges of developing and validating PK and immunogenicity assays to support pre-clinical and clinical comparability studies for biosimilars

This entry is part 9 of 10 in the series Bioanalysis for Biosimilars Development

apDoi: 10.4155/FSEB2013.14.134


Xiao-Yan Cai*
Executive Director Division of Global Bioanalytical Services for Large Molecules
WuXi AppTec
107 Morgan Lane, Plainsboro
NJ 08536, USA
Tel.: +1 609 418 0117

Dominique Gouty
Vice President Business Operations
BioAgilytix Labs
2300 Englert Drive, Durham,
NC 27713, USA
Tel.: + 1 919 287 1526

*Corresponding Author

About the Authors

Xiao-Yan Cai

Xiao-Yan Cai, Ph.D, is Executive Director at WuXi AppTec Global Bioanalytical Services (BAS, Shanghai, China) for large molecules. Prior to her current role, she was Director at Merck’s Biologics Bioanalytical Development division. She has over 20 years of experience in the pharmaceutical industry and specializes in large-molecule bioanalysis (PK, Immunogenicity and biomarker assays).She has been invited to speak at many conferences on numerous topics in the bioanalytical testing area (e.g., immunogenicity assay challenges for biosimilars, cell-based neutralizing anti-drug antibody [ADA] assays, overcoming drug tolerance challenges for ADA assays, and ultrasensitive PK assays to quantify low concentration of drug in serum samples). She is among the industry leaders for bioanalytical assay development and validation for biosimilars.

Dr. Cai holds a M.D. from Beijing Medical University in China and a Ph.D. in Biochemistry and Molecular Biology from the University of Medicine and Dentistry of New Jersey, which is now part of The Rutgers University in New Jersey (USA).

Dominique Gouty

Dr Dominique Gouty is the Vice President of Business Operations at BioAgilytix Laboratories (North Carolina, USA), where she holds key roles in both technical and commercial biopharmaceutical services. She has over 20 years of industry experience and a career spanning R&D, clinical operations, and manufacturing in several multi-national pharmaceutical organizations such as Eli Lilly and J&J, as well as smaller biotech companies and CROs.

Dr Gouty is the leading expert in key subjects concerning preclinical and clinical bioanalysis for novel therapeutic biologics and biosimilars. She is regularly invited to present at conferences and publishes key articles and e-books concerning effective routes to robust and rigorous immunoassays. She has extensive experience ensuring strict GLP compliance for bioanalytical assays and has expert knowledge on the evolution of the US FDA, EMA, and other regulatory agencies.

Case studies: Challenges of developing and validating PK and immunogenicity assays to support pre-clinical and clinical comparability studies for biosimilars


Establishing biosimilarity of a biosimilar drug to its originator presents unique challenges as compared with small-molecule generic drugs. In addition to assessing structural and chemical characteristics of the molecule, its efficacy and safety must also be compared with its originator through pre-clinical and clinical comparability studies. Therefore, it is critical to develop and validate PK bioanalytical assays, which can assess biosimilar and originator, as well as their anti-drug antibodies ‘similarly’ in biological matrices.


One of the most challenging aspects of developing biosimilar therapeutics is to establish biosimilarity to its originator. However, demonstrating ’biosimilarity’ of biosimilar to its originator is not trivial for a variety of reasons. Compared with conventional generic drugs (i.e., chemical or small-molecule drugs), biologics are much more complex in terms of their structure, and are also bigger. The complexity of biologics can also further be affected by a number of additional factors (e.g., cell lines chosen, fermentation condition, purification process, formulation, as well as storage containers/conditions and packaging), which can decrease bioactivity over time, increasing impurity levels (aggregation and/or post-translational modifications). Such changes can potentially lead to serious consequences.

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