In Vitro Biological Characterization of Recombinant Insulin Aspart from Biogenomics and Originator Insulin Aspart.

IF 5.4 2区医学 Q1 IMMUNOLOGY BioDrugs Pub Date : 2023-09-01 DOI:10.1007/s40259-023-00607-4

Akshay G Mishra, Rutuja B Deshmane, Damodar K Thappa, Jeseena Lona, Nikhil S Ghade, Sanjay M Sonar, Archana R Krishnan

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Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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^®.

Conclusion: The biological characterization studies of BGL-ASP demonstrated high binding and functional similarity to NovoRapid^®.

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重组胰岛素天冬氨酸的体外生物学特性研究。

背景:生物测定法用于鉴定新的或化学未知化合物的药理活性，以及它们的不良影响，包括毒性。还需要进行生物测定，以确保重组生物制剂的质量、安全性和有效性，以确认其与原制剂的生物相似性。在本研究中，生物仿制药和创新药之间的分析相似性是通过体外生物测定来确定的。目的:本研究的目的是通过相关的生物学分析，比较BioGenomics公司的重组胰岛素天门冬氨酸及其前身胰岛素天门冬氨酸的体外特性。方法:采用体外受体结合、受体自磷酸化、葡萄糖摄取、有丝分裂潜能等方法分析BioGenomics公司生产的重组胰岛素-天门苷(BGL-ASP)和诺和诺德公司生产的参比药物NovoRapid®(RMP)的生物学特性。胰岛素受体结合研究了最先进的方法，表面等离子体共振(SPR)的生物分子相互作用。受体自磷酸化试验测量细胞裂解物中磷酸化的胰岛素受体。葡萄糖摄取试验测量胰岛素存在下3T3-L1细胞对葡萄糖的摄取。通过检测细胞内脂滴的积累，研究3T3-L1细胞的脂肪生成。用MCF-7细胞增殖实验研究有丝分裂效应。通过测量在胰岛素存在下血糖的突然下降，进行了兔生物特性试验。结果:结合研究表明，BGL-ASP的亲和力与NovoRapid具有高度可比性。胰岛素受体自磷酸化、葡萄糖摄取和脂肪生成与RMP高度相似。BGL-ASP的有丝分裂实验没有显示任何增殖作用，与RMP相当。体内生物特性试验表明，BGL-ASP与创新者NovoRapid®高度相似。结论:BGL-ASP与NovoRapid具有高结合性和功能相似性。

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来源期刊

BioDrugs 医学-免疫学

CiteScore

12.60

自引率

2.90%

发文量

审稿时长

>12 weeks

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