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Review
. 2023 Nov;17(6):1649-1661.
doi: 10.1177/19322968221105864. Epub 2022 Jul 11.

Understanding Biosimilar Insulins - Development, Manufacturing, and Clinical Trials

Lutz Heinemann  1 , Melanie Davies  2 , Philip Home  3 , Thomas Forst  4 , Tina Vilsbøll  5 , Oliver Schnell  6
Affiliations
Review

Understanding Biosimilar Insulins - Development, Manufacturing, and Clinical Trials

Lutz Heinemann et al. J Diabetes Sci Technol. 2023 Nov.

Abstract

Background: A wave of expiring patents for first-generation insulin analogues has created opportunities in the global insulin market for highly similar versions of these products, biosimilar insulins. Biologics are generally large, complex molecules produced through biotechnology in a living system, such as a microorganism, plant cell, or animal cell. Since manufacturing processes of biologics vary, biosimilars cannot be exact copies of their reference product but must exhibit a high degree of functional and structural similarity. Biosimilarity is proven by analytical approaches in comparative assessments, preclinical cell-based and animal studies, as well as clinical studies in humans facilitating the accumulation of evidence across all assessments. The approval of biosimilars follows detailed regulatory pathways derived from those of their reference products and established by agencies such as the European Medicines Agency and the US Food and Drug Administration. Regulatory authorities impose requirements to ensure that biosimilars meet high standards of quality, safety, and efficacy and are highly similar to their reference product.

Purpose: This review aims to aid clinical understanding of the high standards of development, manufacturing, and regulation of biosimilar insulins.

Methods: Recent relevant studies indexed by PubMed and regulatory documents were included.

Conclusions: Driven by price competition, the emergence of biosimilar insulins may help expand global access to current insulin analogues. To maximize the impact of the advantage for falling retail costs of biosimilar insulins compared with that of reference insulins, healthcare professionals and insulin users must gain further awareness and confidence.

Keywords: biologics; biosimilar; clamp; clinical trials; diabetes; insulin; insulin therapy; manufacture; pharmacodynamic; pharmacokinetic; regulation.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Prof. Lutz Heinemann is member of an advisory board of Becton Dickinson, Convatec, Roche Diabetes Care, Sciarc and Member of the Board of Lifecare.Prof. Melanie Davies has acted as consultant, advisory board member, and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk, Sciarc, and Sanofi; an advisory board member and speaker for AstraZeneca; an advisory board member for Janssen, Lexicon, Pfizer, and ShouTi Pharma Inc; and a speaker for Napp Pharmaceuticals, Novartis, and Takeda Pharmaceuticals International, Inc. She has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca, and Janssen.Prof. Philip Home or institutions with which he is associated have received funding for his research, lecturing, or advisory activities from Viatris, Sanofi, Gan & Lee, Sciarc, and Merck Inc in regard of biosimilar insulins, and from Ely Lilly, Novo Nordisk, and Sanofi in regard of originator insulins.Prof. Thomas Forst is member of an advisory board of Astra Zeneca; Atrogi, Bayer; Cipla, Eli Lilly; Eyesense; Fortbildungskolleg; Novo Nordisk; Pfizer; Sanofi; Bayer; Remynd, Roche; Eyesense; Sciarc and member of the speaker Panel of Astra Zeneca; Boehringer Ingelheim, Berlin Chemie; Cipla, Daiichi-Sankyo, Eli Lilly; Fortbildungskolleg; MSD; Novartis, Novo Nordisk; SanofiProf. Tina Vilsbøll has served on scientific advisory panels and/or speakers’ bureaus or has served as a consultant to and/or received research support from AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, MSD/Merck, Mundipharma, Novo Nordisk, Sanofi, Sciarc, and Sun Pharmaceuticals.Prof. Oliver Schnell is a founder and CEO of Sciarc GmbH.

Figures

Figure 1.
Figure 1.
The five steps in biosimilar development.
Figure 2.
Figure 2.
Manufacturing steps in the production of recombinant insulin products.
See this image and copyright information in PMC

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