BioGenomics Ltd., Thane, Maharashtra, 400610, India.
BioDrugs. 2023 Sep;37(5):709-719. doi: 10.1007/s40259-023-00607-4. Epub 2023 Jun 7.
Bioassays are used to identify the pharmacological activity of new or chemically unknown compounds, as well as their undesirable effect, including toxicity. Biological assays are also required to ensure the quality, safety, and efficacy of recombinant biologics to confirm its biosimilarity to its originator. In the present study, analytical similarity between the biosimilar and its innovator is established by in vitro bioassays.
The objective of this study was to show the comparative in vitro characterization of the recombinant insulin aspart from BioGenomics with its originator insulin aspart, using relevant biological assays.
In vitro assays such as receptor binding, receptor autophosphorylation, glucose uptake, and mitogenic potential were analyzed for biological characterization of BioGenomics recombinant insulin aspart (BGL-ASP) manufactured by BioGenomics Limited and NovoRapid as the reference medicinal product (RMP) manufactured by Novo Nordisk. Insulin receptor binding was studied by a state-of-the-art method, surface plasmon resonance (SPR) for biomolecular interactions. The receptor autophosphorylation assay measures the phosphorylated insulin receptor in cell lysates. The glucose uptake assay measures the uptake of glucose by 3T3-L1 cells in the presence of insulin. Lipogenesis was studied in treated 3T3-L1 cells by detecting the accumulation of lipid droplets in the cells. Mitogenic effect was studied by cell proliferation assay using MCF-7 cells. A rabbit bioidentity test was performed by measuring the sudden decrease in blood glucose in the presence of insulin.
The binding studies showed that the affinity of BGL-ASP was highly comparable to NovoRapid. Insulin receptor autophosphorylation, glucose uptake, and lipogenesis demonstrated high similarity to the RMP. The mitogenic assay for BGL-ASP did not show any proliferative effect and was comparable to the RMP. The in vivo bioidentity test showed that the BGL-ASP is highly similar to the innovator, NovoRapid.
The biological characterization studies of BGL-ASP demonstrated high binding and functional similarity to NovoRapid.
生物测定法用于鉴定新的或化学未知化合物的药理活性以及其不良作用，包括毒性。还需要生物测定法来确保重组生物制剂的质量、安全性和疗效，以确认其与原创药的生物相似性。在本研究中，通过体外生物测定法确定了类似物与其原创药之间的分析相似性。
本研究旨在通过相关的生物学测定，展示 BioGenomics 的重组门冬胰岛素与原创药门冬胰岛素的体外比较特征。
通过表面等离子体共振（SPR）等体外测定法，对 BioGenomics 生产的重组门冬胰岛素（BGL-ASP，BGL）和 Novo Nordisk 生产的诺和锐（RMP）进行胰岛素受体结合、受体自动磷酸化、葡萄糖摄取和促有丝分裂潜力等生物特征分析。采用最先进的表面等离子体共振（SPR）技术研究胰岛素受体结合。受体自动磷酸化测定法测量细胞裂解物中磷酸化的胰岛素受体。葡萄糖摄取测定法用于测量胰岛素存在下 3T3-L1 细胞对葡萄糖的摄取。通过检测细胞内脂滴的积累来研究脂肪生成。采用 MCF-7 细胞的细胞增殖测定法研究促有丝分裂作用。通过测量胰岛素存在下血糖的急剧下降，进行兔生物同一性试验。
结合研究表明，BGL-ASP 的亲和力与诺和锐高度相似。胰岛素受体自动磷酸化、葡萄糖摄取和脂肪生成与 RMP 高度相似。BGL-ASP 的促有丝分裂测定法没有显示任何增殖作用，与 RMP 相当。体内生物同一性试验表明，BGL-ASP 与原创药诺和锐高度相似。
BGL-ASP 的生物学特征研究表明，它与诺和锐具有高度的结合和功能相似性。
