BioGenomics Limited, Thane, Maharashtra, 400610, India.
Sci Rep. 2024 Feb 20;14(1):4224. doi: 10.1038/s41598-024-54819-x.
Biosimilar insulin analogues are increasing market access for diabetic patients globally. Scientific establishment of biosimilarity is cornerstone of this key change in the medical landscape. BGL-ASP is a biosimilar insulin aspart developed by BioGenomics Limited, India. BioGenomics has considered a stepwise approach in generating the totality of evidence required to establish similarity with reference product. Insulin aspart is a recombinant rapid-acting human insulin analogue utilised in the treatment of type-1 and type-2 diabetes mellitus. The single amino acid substitution at position B28 where proline is replaced with aspartic acid results in a decreased propensity to form hexamers, thus increasing the absorption rate on subcutaneous administration compared to native insulin. In order to establish the safety and efficacy of BGL-ASP, the critical quality attributes (CQAs) of BGL-ASP are identified based on the impact created on biological activity, pharmacokinetic/pharmacodynamic (PK/PD), immunogenicity and safety. The CQAs of insulin aspart are related to product structure, purity and functionality and are characterised using a series of state-of-the-art orthogonal analytical tools. The primary protein sequence, the secondary, tertiary and quaternary structure are found to be highly similar for BGL-ASP and reference product. The product related impurities of insulin aspart and the assay content are determined using high performance liquid chromatography (HPLC) based analysis and is similar for BGL-ASP and reference insulin aspart sourced from United States of America (US), Europe Union (EU) and India. The safety, efficacy and immunogenicity of BGL-ASP is also found to be comparable with reference product and is confirmed through the clinical trials conducted as recommended by International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH) and European Medicines Agency (EMA) guidelines. The data encompassed in this study demonstrates that reference insulin aspart and BGL-ASP are highly similar in terms of structural, physicochemical, and biological properties, thus confirming its safety and efficacy for usage as potential alternative economical medicinal treatment for diabetes mellitus.
生物类似胰岛素类似物正在全球范围内增加糖尿病患者的药物可及性。生物类似性的科学确证是医疗领域这一关键变化的基石。BGL-ASP 是印度生物基因组有限公司开发的一种胰岛素类似物。生物基因组公司在生成建立与参比产品相似性所需的全部证据方面，采用了逐步的方法。胰岛素类似物是一种用于治疗 1 型和 2 型糖尿病的重组速效人胰岛素类似物。在 B28 位置的单个氨基酸取代，脯氨酸被天冬氨酸取代，导致六聚体形成的倾向降低，从而与天然胰岛素相比，皮下给药的吸收速度增加。为了确定 BGL-ASP 的安全性和疗效，根据对生物活性、药代动力学/药效学（PK/PD）、免疫原性和安全性的影响，确定 BGL-ASP 的关键质量属性（CQAs）。胰岛素类似物的 CQAs 与产品结构、纯度和功能有关，使用一系列最先进的正交分析工具进行表征。BGL-ASP 和参比产品的一级蛋白质序列、二级、三级和四级结构高度相似。胰岛素类似物的产品相关杂质和含量测定采用基于高效液相色谱（HPLC）的分析方法，BGL-ASP 和来自美国、欧盟和印度的参比胰岛素类似物的结果相似。BGL-ASP 的安全性、疗效和免疫原性也与参比产品相当，这通过国际人用药品注册技术协调会（ICH）和欧洲药品管理局（EMA）指南推荐的临床试验得到证实。本研究涵盖的数据表明，参比胰岛素类似物和 BGL-ASP 在结构、理化和生物学特性方面高度相似，从而证实其安全性和疗效，可作为潜在的经济实惠的糖尿病治疗替代药物。
