Biosimilars: linking quality data to clinical outcomes

L.A. Halim

Research output: ThesisDoctoral thesis 1 (Research UU / Graduation UU)


The aim of this study was to establish a link between quality attributes of biosimilars and potential clinical outcomes with regards to safety and immunogenicity. As we have access to multiple biosimilar and copy biologic products as well to patient data, the research involved linking comparative qualitative data of filgrastim and epoetin to clinical safety and immunogenicity. Common assays, which included sodium dodecyl sulfate polyacrylamide gel electrophoresis in combination with western blot, high performance size-exclusion chromatography, asymmetrical flow field-flow fractionation, capillary zone electrophoresis, iso-electric focusing, host cell protein impurities, endotoxin contamination, and potency testing were used to characterize biosimilar, copy and innovator products. With respect to filgrastim, except for the specific activities of the two copy filgrastim products, we found no clinically significant differences in product quality between the copy, the biosimilar, and the innovator filgrastim products. Our study also demonstrates comparable quality of biosimilar epoetin products compared to the innovator with some degree of variations in epoetin content, isoform profiles and potency found between products as well as among batches of single products. In contrast, some of the copy epoetin products from the Thai drug market did differ significantly from the innovator product, with higher impurities e.g. aggregation and host cell protein observed. Our clinical data indicate a higher incidence of pure red cell aplasia among patients administered these copies. These results suggest a potential link between quality attributes of biosimilars and potential clinical outcomes. More importantly, this may contribute to a future in which the biosimilars will be increasingly considered as classical generics.
Original languageEnglish
Awarding Institution
  • Utrecht University
  • Schellekens, H., Primary supervisor
  • Brinks, V., Co-supervisor
Award date12 Oct 2016
Print ISBNs978-90-393-6618-4
Publication statusPublished - 12 Oct 2016


  • recombinant human erythropoietin
  • physicohemical properties
  • immunogenicity
  • pure red cell aplasia


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