Abstract
Purpose :
SB11 is a proposed biosimilar to reference ranibizumab, which is currently being reviewed for the marketing authorization, developed for the treatment of ocular diseases. The objective of this study was to assess the structural and functional similarity between SB11 and reference products obtained from United States (US-ranibizumab) and European Union (EU-ranibizumab).
Methods :
A comprehensive structural and functional characterization was performed utilizing state-of-the-art analytical methods. Comparisons included the following: primary structure related to amino acid sequence and post-translational modifications; higher order structure; product-related substances and impurities including size and charge variants; and protein concentration. In addition, biological characterization included a series of bioassay such as vascular endothelial growth factor (VEGF)-A binding assay, cell-based VEGF-A neutralization assay, and human umbilical vein endothelial cells (HUVEC) anti-proliferation assay.
Results :
The amino acid sequence of SB11 was identical to that of US- and EU-ranibizumab. SB11 was shown to be indistinguishable from the reference products with respect to post-translational modification profiles and higher order structures. Product-related size and charge variants and aggregates were also similar. Functionally, SB11 could not be distinguished from US- and EU-ranibizumab by using a set of bioassays and binding assays covering a broad range of VEGF-related functional activities. The relative binding activity or potencies were calculated relative to the reference standard prepared from one lot of reference product. The binding activity of SB11 representative batches analyzed using VEGF-A binding assay were evaluated as 98% (RSD=2%). The potencies of SB11 representative batches analyzed using HUVEC anti-proliferation and VEGF-A neutralization assay were evaluated as 101% (RSD=5%) and 99% (RSD=4%), respectively.
Conclusions :
Based on the comprehensive analytical similarity assessment, SB11 is highly similar to the US- and EU-ranibizumab with respect to structural, physicochemical, and biological properties.
This is a 2021 ARVO Annual Meeting abstract.