Trastuzumab Charge Variants: a Study on Physicochemical and Pharmacokinetic Properties
Background: Post-translational modifications in bioprocessing and
storage of recombinant mAbs are the main sources of charge variants.
While the profile of these kinds of variants is considered an important
quality attribute of therapeutic mAbs, there is controversy about their
direct role on safety and efficacy. In this study, the physicochemical
and PK properties of separated
charge variants belonging to a trastuzumab potential biosimilar were examined.
Methods:
The APs, BPs, and main variants of trastuzumab were separated and
enriched by semi-preparative WCX. A panel of analytical techniques was
utilized to characterize the physicochemical properties of these
variants. The binding affinity to HER2 and FcγRs and the PK parameters
were evaluated for each variant.
Results: Based on the results,
the charge variants of the proposed biosimilar had no significant
influence on the examined efficacy and PK parameters.
Conclusion: During the development and production of biosimilar mAbs, studying the effects of their charge variants on efficacy and PK parameters is needed.