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KMID : 1146920200500040413
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Journal of Pharmaceutical Investigation
2020 Volume.50 No. 4 p.413 ~ p.423
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Receptor-binding hydrogen?deuterium exchange mass spectrometry as an additional measurement of biosimilarity
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Treuheit Nicholas A.
Crawford Nicholas F.
Maki Steven
Payne Jason
Allen Jeff
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Abstract
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Purpose: Biosimilars can effectively reduce the cost of healthcare by providing a new source of competition for original drugs. A cornerstone of biosimilar development is assembling a comprehensive package of analytical data that demonstrates physicochemical biosimilarity to justify a shorter regimen of clinical trials. The purpose of the present work was to present part of a biosimilarity data package comparing Pfenex pegfilgrastim to its reference, Amgen’s Neulasta™ and to highlight a deuterium exchange experiment that can be used as part of the analytical tool box to demonstrate biosimilarity.
Methods: We used circular dichroism (CD), fluorescence, biolayer interferometry (BLI), and hydrogen?deuterium exchange (HDX) mass spectrometry experiments to analyze structural similarity between Pfenex pegfilgrastim and its reference, Amgen’s Neulasta™. In particular, we incorporated a novel HDX experiment comparing binding to the receptor by Pfenex pegfilgrastim or Neulasta™.
Results: The characterization experiments showed a high degree of similarity between the molecules, from secondary structure (CD/fluorescence), binding (BLI), and deuterium uptake in free and bound forms (HDX). Notably, the receptor-binding experiment found seven peptides that were similarly protected upon binding to both pegfilgrastim molecules.
Conclusion: These select experiments are a subset of the required characterization to demonstrate similarity, but they represent a progression of structural analysis that is enhanced and strengthened by a novel HDX experiment. This method improves our understanding of this interaction and gives us another analytical tool for demonstrating biosimilarity that should be adaptable for use with other biosimilar products in the future.
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KEYWORD
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Biosimilar(s), Structural similarity, Hydrogen?deuterium exchange mass spectrometry
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