Insulin manufacture

Humulin (R, L, N, U, 50/50, and 70/30). Human insulin manufactured by Eli Lilly and Company has the trademark Humulin and is available in six formulations—Regular (R), NPH (N), Lente (L), Ultralente (U), 50% human insulin isophane suspension (NPH)/50% human insulin injection (buffered regular) (50/50), and 70% human insulin isophane suspension (NPH)/30% human insulin injection (buffered regular) (70/30). 

Historically, commercial insulin in the USA contained beef or pork insulin. Beef insulin differs by three amino acids from human insulin, whereas only a single amino acid distinguishes pork and human insulins (Figure 41-1). The beef hormone is slightly more antigenic than pork insulin in humans. Of the insulins manufactured from animal sources, only purified pork insulin is still available and it requires special ordering. 

Historically, insulin came from either beef or pork sources. Beef insulin differs by three amino acids and pork by one amino acid when compared to human insulin. Manufacturers in the United States have discontinued production of beef and pork source insulins as of December 2003, and now exclusively use recombinant DNA technology to manufacture insulin. Eli Lilly and Aventis currently use... 

Occasional patients have antibodies to injected insulin, but the significance of the antibodies is minimal. Human insulin therapy has not totally eliminated insulin allergies, although most patients have a local reaction that will dissipate over time. If the allergic reaction does not improve or is systemic, insulin desensitization can be carried out. Protocols for desensitization are available from major insulin manufacturers. While more common in the animal insulin era, lipohypertrophy is still seen in some patients with longstanding type 1 DM. Such patients give their insulin injections in the same site to minimize discomfort. Because insulin absorption from an area of lipohypertrophy is unpredictable, avoidance of injections into these areas is mandatory. 

Since the mid-1980s human insulin, manufactured through a recombinant DNA technique, has become available for clinical use. With this technique insulin is manufactured by producing the A- and B-chains in separate bacterial cultures of Escherichia coli... 

Insulin is a hormone manufactured by the beta cells of the pancreas. It is the principal hormone required for the proper use of glucose (carbohydrate) by the body. Insulin also controls the storage and utilization of amino acids and fatty acids. Insulin lowers blood glucose levels by inhibiting glucose production by the liver. 

Generic Name (Insulin) Brand Manufacturer Strength Onset (minutes) Peak (hours) Duration (hours) Administration Options... 

Table 11.3 Native and engineered human insulin preparations that have gained approval for general medical use. Reproduced in updated form with permission from Walsh, G. 2005. Therapeutic insulins and their large-scale manufacture. Applied Microbiology and Biotechnology, 67, 151-159...

Walsh, G. 2005. Therapeutic insulins and their large scale manufacture. Applied Microbiology and Biotechnology 67, 151-159. 

Insulin was originally (since the 1930s) obtained from porcine and bovine extracts. Bovine insulin differs from human insulin by three amino acids, and it can elicit an antibody response that reduces its effectiveness. Porcine insulin, however, differs in only one amino acid. An enzymatic process can yield insulin identical to the human form. Currently, insulin is produced via the rDNA process it was the first recombinant biopharmaceutical approved by the FDA in 1982. The recombinant insulin removes the reliance on animal sources of insulin and ensures that reliable and consistent insulin is manufactured under controlled manufacturing processes. A description of diabetes meUitus and insulin is presented in Exhibit 4.13. 

Recombinant DNA drug production has been a success story, but the technology does have its drawbacks and disadvantages. For example, the use of bacterial plasmids and, less commonly, viruses, as vectors for the insertion of genes into host cells has its limitations. While such methods work well for smaller drug molecules, such as insulin, they are much less effective in the production of larger, more complex proteins that constitute many of the drugs that chemists would like to manufacture synthetically. 

In some ways, the use of animals (almost always mammals) as substitutes for bacteria in the recombinant DNA production of drugs is a natural and obvious extension of the techniques originally developed for the manufacture of insulin, human growth hormone, and other pharmaceuticals. Live animals have a built-in production... 

Mixing of insuiins-The effects of mixing insulin aspart or lispro with insulins of animal source or insulin preparations produced by other manufacturers have not been studied (see Warnings). 

Manufacturer premixed formulations remain stable for 1 month at room temperature or for 3 months refrigerated. These mixtures also can be stored in prefilled plastic or glass syringes for 1 week to possibly 14 days under refrigeration. Slightly agitate to remix the insulins. Check for normal appearance. 

Generai This human insulin product differs from animal-source insulins because it is structurally identical to the insulin produced by the body s pancreas and because of its unique manufacturing process. 

Make any change of insulin cautiously and only under medical supervision. Changes in purity, strength, brand (manufacturer), type (eg, regular, NPH, lente), species (beef, pork, beef-pork, human), or method of manufacturer (rDNA vs animal-source insulin) may result in the need for a change in dosage. 

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