Background Biosimilars are follow-on versions of peptide biological drugs, and differences in manufacturing and formulation can result in variations in physicochemical and clinical profiles. The European Medicines Agency (EMA) has set stringent standards (Ph Eur) that must be met for the approval of a biosimilar.
Purpose Standards of manufacture may differ between biosimilars approved via EMA pathways, and copy biologicals that lack approval pathways. Therefore, we undertook comparative characterisation tests of a range of biosimilar products from different global regions to determine if variations exist. This study is the first of its kind.
Materials and Methods Samples of Nivestim (Ni), Neupogen (Ne), Tevagrastim (T), Ratiograstim and Zarzio (Z) were obtained from the EU region; and Leucostim (L), GeSysin (G), Filgen (F) and Neukine (Nk) were obtained from the Middle East and Africa (MENA) region. All samples were within the expiry date. Samples were analysed for impurities using iso-electric focussing (IEF) to identify differences in charge, size-exclusion high-performance liquid chromatography (SEC-HPLC) to identify differences in higher molecular weight impurities, reverse phase HPLC (RP-HPLC) to identify differences in total and individual related impurities, and ion chromatography (IC) to detect differences in f-met filgrastim and related, more acidic, impurities.
Results All biosimilars met EMA standards for IEF and SEC-HPLC analysis. Total impurities (RP-HLPC) for the EU products were in the range 1.8–2.6% and within EMA requirements (≤3.5%); however, the MENA samples contained impurities in the range 5.9% (G) – 8.2% (L), which is beyond the Ph Eur range. IC analysis revealed f-met and acidic impurities to be <0.20% for most EU products (threshold 1.0%) and 0.4% for Ne. However, for MENA compounds, these impurities comprised 0.4% (Nk) – 1.7% (G) of the samples.
Conclusions Copy biologicals from MENA have higher levels of impurities than biosimilars from the EU and do not meet EMA standards for approval.
No conflict of interest.
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