Insulin Production Technology
Insulin is a hormone that controls blood glucose levels produced by the beta cells in the pancreas. As a medication, insulin was discovered by Frederick Banting and Charles Best in 1921, for which Banting was awarded a Nobel Prize in 1923. The insulin production process involves manipulating the biological precursor to insulin and cultivating it inside bacteria using specialized technology.
Which insulin equipment do you need?
High-frequency vibratory mixer
Acoustic cell retention system
Autoclavable glass bioreactor
Autoclavable stainless steel bioreactor
Photobioreactor for plant growth
Lab scale Bioreactor controller
Small-scale bioreactor controller
Scalable bioreactor controller
Dissolved Oxygen sensor
Steam-in-place bioreactor systems
Micro-Flask
Mini bioreactors
pH Sensor
Resonance Acoustic Mixer
Single-use bioreactor Appliflex
Single-use bioreactor CellReady 3L
Single use bioreactor Hyclone
Spiral jet mill
Superheated water shower autoclave
Dry heat depyrogenation oven
Sterility test isolators
3D disposable bags for bioprocesses
Disposable tank liners
Disposable manifold bags for bioprocesses
Normal flow filtration sets for bioprocesses
Disposable mixer bags for bioprocesses
Disposable pillow bags for bioprocesses
Biocompatible tubing for peristaltic pumps
Y sets tubing for bioprocesses
Disposable tubing for manifolds in bioprocesses
Automated single use tangential flow filtration system
Semi-automated tangential flow filtration system
Semi-automated normal flow filtration system
Bag holder and weighing platform for bioprocesses
Lab scale tangential flow filtration system
Lab scale normal flow filtration system
Automated dispensing system for bioprocesses
Single-use pressure sensor
Single-use conductivity sensor
Single-use temperature sensor
Automated cell culture clarification system
High-speed aseptic injectable vial filling machine
Disposable monolithic columns
Short bed monolithic columns for analytics
Plasmid process pack for your pDNA purification process
Purification screening kit for large biomolecules
Compact H2O2 disinfection system
24 fully controlled bioreactors in a microtiter format
Flexible automatic inspection machine for syringes
Flexible automatic inspection machine for ampoules, vials, cartridges
Small automatic inspector for ampoules, vials, or cartridges
Semi-automatic inspection machine for ampoules, vials or cartridges
Visual and HVLD inspection for ampoules, vials and cartridges
Closed restricted access barrier system
Single use bioreactor
Bioreactor software
Bioprocess control software
Optical Dissolved Oxygen Sensors
Complete bioreactor system
Lab-scale radial chromatography columns for virus validation
Pre-packed and pre-validated chromatography columns
Automated bubble traps for chromatography
Cold forming aluminum blister machine for capsules
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The differences between animal-derived insulin and human insulin
Insulin injections are used for managing blood sugar levels in individuals who can’t naturally produce insulin. For many years, using insulin derived from animals, mainly porcine or bovine pancreases was the norm, but the production of human insulin became a more popular alternative since its discovery in the 1980s. Manufacturing biosynthetic human insulin via gene technologies is a preferred method for not having to depend on animals as well as the possibility to produce unlimited amounts by multiplying the insulin gene inside bacteria.
Aside from production efficiency, as extracting large amounts from animal tissue is challenging, some issues with animal-derived insulin production are related to the raw animal tissues and diseases such as Bovine Spongiform Encephalopathy (BSE) and Transmissible Spongiform Encephalopathy (TSE) and possible cross-contamination through injections. Furthermore, the chemical differences between human and animal insulin can lead to antibody attacks, inactivation and inflammation.
However, a shortage of animal-sourced insulin in developed countries is a concern for a small number of individuals who experience severe hypoglycemic episodes when using biosynthetic insulin, and generally feel healthier when undergoing an animal-derived insulin treatment.
The steps and technology in recombinant insulin production processes
Recombinant DNA is a technology for the large-scale production of insulin by inserting the human gene which carries codes for the protein insulin into a plasmid of a simple bacteria, most commonly Escherichia coli. Producers then add ligase, an enzyme that acts like glue to help the plasmid stick to the bacterium’s DNA. The bacteria undergo a fermentation process inside a large fermentation tank, where millions of bacteria replicate every 20 minutes. The insulin harvest starts by adding a mixture of lysozyme which digests the outer layer of the cell wall and a detergent mixture which separates the fatty cell wall membrane.
The insulin is separated from the bacterium’s DNA with the help of a cyanogen bromide treatment which splits protein chains at the methionine residues. An oxidizing agent is added and the mixture is placed in a centrifuge to separate cell components. The DNA mixture is purified by using one of the following techniques: ion-exchange column, reverse-phase high-performance liquid chromatography or a gel filtration chromatography column. Finally, the purified substance is ready for medical use.
The future of insulin patents and treatment delivery
Although the use of insulin pens is a practical therapy due to their reusable nature, ability to increase patient compliance and accuracy, and there are innovative solutions to enhance the delivery of insulin in the future. An alternative for diabetes care would be oral application, however, scientists are looking for ways to avoid enzymatic degradation upon consumption. Solutions can be found in nanoparticle-based approaches which protect insulin from gastrointestinal conditions and enhance the permeability of the enzyme.
A further option is the bioresponsive insulin delivery system, which accelerates insulin release with increasing glucose levels. Furthermore, manufacturers are working on the production of inhaled insulin devices, with insulin particles small enough to reach the deep lung and pass into the bloodstream. Another aerosol option is buccal insulin, a spray absorbed through the inner cheek wall. Finally, absorbing insulin through the skin with the help of insulin patches is another idea in development.
Transgenic plants as a solution for high demand
The insulin production process and its current manufacturing technologies struggle to keep up with the steadily increasing demand for affordable insulin due to a rising number of patients with diabetes. This is especially the case in the United States. One of the most effective alternatives is the manufacture of recombinant human insulin from the plant Arabidopsis Thaliana and its oilseeds. Plant-based insulin is easy to produce, cost-effective, free from human pathogens and involves high-quality protein processing.
The oilseeds are genetically engineered with the recombinant protein targeting oil bodies and then processed by separating oil bodies via liquid-liquid phase to reduce chromatography steps in the purification of insulin. Transgenic plants can produce a high level of biologically active proinsulin and it can further be enzymatically treated in vitro which is an economic method for mass production.