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Insulin

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Pharmaceutical Biotechnology

Abstract

Insulin was discovered by Banting and Best in 1921 (Bliss 1982). Soon afterwards manufacturing processes were developed to extract the insulin from porcine and bovine pancreas. From 1921 to 1980, efforts were directed at increasing the purity of the insulin and providing different formulations for altering time action for improved glucose control (Brange 1987a, b; Galloway 1988). Purification was improved by optimizing extraction and processing conditions and by implementing chromatographic processes (size exclusion, ion exchange, and reversed-phase (Kroeff et al. 1989)) to reduce the levels of both general protein impurities and insulin-related proteins such as proinsulin and insulin polymers. Formulation development focused on improving chemical stability by moving from acidic to neutral formulations and by modifying the time-action profile through the uses of various levels of zinc and protamine. The evolution of recombinant DNA technology led to the widespread availability of human insulin, which has eliminated issues with sourcing constraints while providing the patient with a natural exogenous source of insulin. Combining the improved purification methodologies and recombinant DNA (rDNA) technology, manufacturers of insulin are now able to provide the purest human insulin ever made available, >98 %. Further advances in rDNA technology, coupled with a detailed understanding of the molecular properties of insulin and knowledge of its endogenous secretion profile, enabled the development of insulin analogs with improved pharmacology relative to existing human insulin products.

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Notes

  1. 1.

    During the preparation of this book chapter, the structure of LY2605541 was disclosed at conference proceedings as insulin lispro PEGylated at LysB28 with a 20kDa PEG (Hansen et al. 2012).

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Authors and Affiliations

  1. Lilly Research Laboratories, Biotechnology Discovery Research, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, 46285, USA

    John M. Beals Ph.D.

  2. Lilly Research Laboratories, Bioproduct Research and Development, Eli Lilly and Company, Indianapolis, IN, USA

    Michael R. DeFelippis Ph.D.

  3. Lilly Research Laboratories, Technical Services and Manufacturing Sciences, Eli Lilly and Company, Indianapolis, IN, USA

    Paul M. Kovach Ph.D.

  4. Lilly Research Laboratories, Medical Affairs, Eli Lilly and Company, Indianapolis, IN, USA

    Jeffrey A. Jackson M.D.

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  1. John M. Beals Ph.D.
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  2. Michael R. DeFelippis Ph.D.
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  3. Paul M. Kovach Ph.D.
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  4. Jeffrey A. Jackson M.D.
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Correspondence to John M. Beals Ph.D. .

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Editors and Affiliations

  1. Department of Pharmaceutical Sciences, Utrecht University, Utrecht, Utrecht, The Netherlands

    Daan J. A. Crommelin

  2. Department of Pharmaceutical Sciences and Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada

    Robert D. Sindelar

  3. Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, College of Pharmacy, Memphis, Tennessee, USA

    Bernd Meibohm

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Beals, J.M., DeFelippis, M.R., Kovach, P.M., Jackson, J.A. (2013). Insulin. In: Crommelin, D., Sindelar, R., Meibohm, B. (eds) Pharmaceutical Biotechnology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6486-0_12

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