Author:
Ghade Nikhil S.,Thappa Damodar K.,Lona Jeseena,Krishnan Archana R.,Sonar Sanjay M.
Abstract
AbstractBiosimilar 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.
Publisher
Springer Science and Business Media LLC
Reference52 articles.
1. Basu, S. et al. Estimation of global insulin use for type 2 diabetes, 2018–30: A microsimulation analysis. Lancet Diabetes Endocrinol. 7(1), 25–33. https://doi.org/10.1016/s2213-8587(18)30303-6 (2018).
2. Hartman, I. Insulin analogs: Impact on treatment success, satisfaction, quality of life, and adherence. Clin. Med. Res. 6(2), 54–67. https://doi.org/10.3121/cmr.2008.793 (2008).
3. Furman, B. L. Aspart insulin. Ref. Module Biomed. Sci. https://doi.org/10.1016/b978-0-12-801238-3.97984-4 (2017).
4. US Food and drug administration. center for drug evaluation and research. Application Number: 20-986: Approval letter for NovoLog (Insulin Aspart [rDNA origin] Injection). In US Food and Drug Administration [Internet]. Silver Spring, MD: US Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-986_NovoLog_Approv.pdf (2000).
5. Vajo, Z. & Duckworth, W. C. Genetically engineered insulin analogs: Diabetes in the new millenium. Pharmacol. Rev. 52(1), 1–10 (2000).