How bio-questionable are the different recombinant human erythropoietin copy products in Thailand?

Liem Andhyk Halim, Vera Brinks, Wim Jiskoot, Stefan Romeijn, Kearkiat Praditpornsilpa, Anunchai Assawamakin, Huub Schellekens

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market. This study aims to assess the quality of rhEPO copy products being used in Thailand.

METHODS: Twelve rhEPO copy products were purchased from pharmacies in Thailand, shipped under controlled cold chain conditions to the Netherlands and characterized using (1) high performance size-exclusion chromatography, (2) asymmetrical flow field-flow fractionation, (3) sodium dodecyl sulfate polyacrylamide gel electrophoresis in combination with (4) Western blotting and additionally tested for (5) host cell protein impurities as well as (6) endotoxin contamination.

RESULTS: Some of the tested rhEPO copy products showed high aggregate levels and contained a substantial amount of protein fragments. Also, one of rhEPO copy products had a high endotoxin level, exceeding the FDA limit.

CONCLUSIONS: Our observations show that some of the tested copy products on the Thai market differ significantly from the originator rhEPO product, Epogen®. This comparison study supports a link between the quality attributes of copy rhEPO products and their immunogenicity.

Original languageEnglish
Pages (from-to)1210-1218
Number of pages9
JournalPharmaceutical Research
Volume31
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • Blotting, Western
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Electrophoresis, Polyacrylamide Gel
  • Erythropoietin
  • Fractionation, Field Flow
  • Humans
  • Recombinant Proteins
  • Thailand

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