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<p>Extensive analytical and functional characterization of a biotherapeutic product is a regulatory requirement, more so for biosimilar products where approval is contingent on the manufacturer’s ability to demonstrate comparability of their product to the corresponding reference product. Typical biotherapeutic formulations contain multiple excipients that are meant to stabilize the product and these can impact certain analytical and functional techniques that are typically used in the above-mentioned characterization and comparability exercises. In this study, we elucidate this interference using Trastuzumab (Tmab) reference product, Herclon, and its commercially available biosimilars, Herzuma and Vivitra, as an example. Excipients were removed one at a time from the drug product and impact of this removal on a spectrum of analytical and functional tools was examined. Removal of certain excipients (Trehalose, L-histidine HCl and Polysorbate 20) was found to impact the results of charge variant analysis (cation exchange HPLC), secondary structure analysis (FTIR and far-UV CD spectroscopy), and tertiary structure analysis (near-UV CD and intrinsic FLR spectroscopy) For charge variants, differences up to 3.62% in basic species were observed, while FTIR spectra in the amide I region were significantly impacted. The intrinsic fluorescence spectra displayed major wavelength maxima shifts of up to 6&#xa0;nm. In view of these results, it is recommended that biosimilar manufacturers consider the impact of differences in formulation in the samples that are being compared as well as the impact of excipient removal, if they are extracting the therapeutic moiety from the drug product for comparability analysis (routinely done by biosimilar manufacturers).</p>

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Removal of Excipients from Drug Product may Impact Antibody Characterization of Monoclonal Antibodies

  • 期刊论文

  • 发表日期：

    2025年5月2日

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  • Kunal Krishna,
  • Deepika Sarin,
  • Drashti Trivedi,
  • Sanghati Bhattacharya,
  • Hesham Refaat,
  • Aziz Ahmad,
  • Reza Nejadnik,
  • Anurag S. Rathore

摘要

Extensive analytical and functional characterization of a biotherapeutic product is a regulatory requirement, more so for biosimilar products where approval is contingent on the manufacturer’s ability to demonstrate comparability of their product to the corresponding reference product. Typical biotherapeutic formulations contain multiple excipients that are meant to stabilize the product and these can impact certain analytical and functional techniques that are typically used in the above-mentioned characterization and comparability exercises. In this study, we elucidate this interference using Trastuzumab (Tmab) reference product, Herclon, and its commercially available biosimilars, Herzuma and Vivitra, as an example. Excipients were removed one at a time from the drug product and impact of this removal on a spectrum of analytical and functional tools was examined. Removal of certain excipients (Trehalose, L-histidine HCl and Polysorbate 20) was found to impact the results of charge variant analysis (cation exchange HPLC), secondary structure analysis (FTIR and far-UV CD spectroscopy), and tertiary structure analysis (near-UV CD and intrinsic FLR spectroscopy) For charge variants, differences up to 3.62% in basic species were observed, while FTIR spectra in the amide I region were significantly impacted. The intrinsic fluorescence spectra displayed major wavelength maxima shifts of up to 6 nm. In view of these results, it is recommended that biosimilar manufacturers consider the impact of differences in formulation in the samples that are being compared as well as the impact of excipient removal, if they are extracting the therapeutic moiety from the drug product for comparability analysis (routinely done by biosimilar manufacturers).