Therapeutic insulins and their large-scale manufacture

  title={Therapeutic insulins and their large-scale manufacture},
  author={Gary Walsh},
  journal={Applied Microbiology and Biotechnology},
  • G. Walsh
  • Published 1 April 2005
  • Biology, Medicine, Engineering
  • Applied Microbiology and Biotechnology
Biotechnological innovations over the past 25 years have underpinned the rapid development of a thriving biopharmaceutical sector. Therapeutic insulin remains one of the most commonly used products of pharmaceutical biotechnology and insulin-based products command annual global sales in excess of $4.5 billion. Innovations in its method of production and in particular the advent of engineered insulin analogues provide a fascinating insight into how scientific and technological advances have… 

Pursuit of a perfect insulin

A broad set of drug candidates, targeting hyperglycaemia plus other disease abnormalities, is now progressing through the clinic, with initial prototypes now reaching the proof-of-concept stage and the first alternatives to injectable delivery have progressed to registration.

Current Applications of Pharmaceutical Biotechnology

Challenges addressed include achieving cell density, protein expression, separations of cells and protein, protein purification, and segmentation of protein production into smaller quantities with the evolution of personalized medicine and products designed for increasingly small patient populations.

Cell factories for insulin production

This review would focus in this review, on various approaches that can be exploited to increase the production of a biologically active insulin and its analogues in E. coli and yeast.

Recombinant Human Insulins – Clinical Efficacy and Safety in Diabetes Therapy

Patients with diabetes could be safely and effectively transferred from animal or semisynthetic human insulin to recombinant human insulin with no change expected in insulin dose, and follow-up after any change of insulin product is recommended to confirm clinical efficacy.

Recent Challenges in Insulin Delivery Systems: A Review

The inhalation delivery system Exubera® has already become clinically available in the United States and Europe for patients with diabetes as non-invasive delivery system.

Therapeutic agents comprising elastic peptides

The therapeutic agents have improvements in relation to their use as therapeutics, including, inter alia, one or more of half-life, clearance and/or persistance in the body, solubility, and bioavailability.

Challenges and Opportunities for the Large-Scale Chemoenzymatic Glycoengineering of Therapeutic N-Glycosylated Monoclonal Antibodies

In vitro chemoenzymatic glycoengineering of variants displaying a homogeneous glycan profile is a trending strategy for ensuring consistent, controlled, and enhanced therapeutic performance, but reported successes are largely limited to small-scale applications.

Lessons learned from biosimilar epoetins and insulins

Two case studies are discussed of three insulin formulations which were physicochemically similar to comparator insulins, but with pharmacokinetic and pharmacodynamic profiles sufficiently different to have potentially serious clinical consequences and that of Eprex, for which an apparently minor change in one formulation caused an upsurge in patients with diabetes and renal failure.

New Peptide Based Therapeutic Approaches

With the advancement of peptide synthesis technologies, improved productivity and reduced metabolism of peptides, along with alternative routes of administration, several bioactive peptides have been developed which are found to be highly functional with many serving as potent agonists and antagonists against several receptors involved in disease progression.



Monomeric insulins obtained by protein engineering and their medical implications

It is reported that it is possible, by single amino-acid substitutions, to make insulins which are essentially monomeric at pharmaceutical concentrations and which have largely preserved their biological activity, capable of giving diabetic patients a more physiological plasma insulin profile at the time of meal consumption.

Research, Development, Production, and Safety of Biosynthetic Human Insulin

The daily treatment of more than two million diabetic patients worldwide with this rDNA human insulin not only demonstrates the value of rDNA technology in providing an important medical product, it is assurance that diabetic patients will have unlimited supplies of this vital hormone as well as potential analogue refinements.

Monomeric Insulins and Their Experimental and Clinical Implications

The development of a series of human insulin analogues with reduced tendency to selfassociation that, because of more rapid absorption, are better suited to meal-related therapy and have the potential to minimize late hypoglycemia.

Insulins today and beyond

Closed-loop insulin delivery-the path to physiological glucose control.

Insulin Lispro (Humalog)

Insulin LISPRO (Humalog(R)) is such an analogue which has gained regulatory approval for general medical use and is identical to human insulin except that the Pro-Lys amino acid sequence at positions B28 and B29 of the native molecule are reversed.

New Developments in Insulin Delivery

The different routes available for insulin administration and the many successful developments that have been made in recent years for improving that particular route for a much better insulin delivery are reviewed.

Alternative routes of insulin delivery

If long‐term safety and efficacy is confirmed, inhalation may become the first non‐subcutaneous route of insulin administration for widespread clinical use, despite overwhelming interest and investment in administering insulin via the oral route.

Oral insulin delivery.

Towards gene therapy of diabetes mellitus.