BIOMM manufacture human insulin. Just saying...
clarify.....
like I am a 5 year old. Never mind.
biomm.com/en/biomm/Founded in 2001, during a split-up process of a major global insulin manufacturer, Biomm is the first and only brazilian company totally focused in biotechnology.
MNKD Brazilian partner. I had forgotten about that....
Genentech announced that they had introduced a human gene for insulin into a safe strain of E. coli bacteria, which then produced the protein.
Genentech partnered with Lilly, which brought
engineered human insulin to the market in 1982 under the brand name Humulin, the first recombinant DNA drug product in the world.
Biotechnology allowed people with diabetes to take insulin that is virtually identical to the body's version. But that was just the beginning for insulin medications. Having the ability to tweak the insulin gene, scientists started to develop new-to-nature forms of insulin—called insulin analogs—such as insulin lispro (Humalog) and insulin glargine (Lantus). Analogs have become increasingly popular among prescribers and patients. Engineers build desirable properties into analogs by tweaking their amino acid sequences in ways that force the body to process them faster or slower than plain human insulin. These new attributes give people with diabetes more options for controlling blood glucose.
Lilly agreed to take Diabetes Forecast on a tour of parts of its Indianapolis insulin production complex. Covering 1.38 million square feet, or 18 soccer fields, the Lilly facilities in Indianapolis are constantly generating Humulin and the insulin analog Humalog.
At Lilly, insulin-making E. coli is grown in 50,000-liter tanks called fermentors. There are more than 5,000 tanks on site.According to Lilly, a batch of insulin from one fermentor could produce a year's supply of insulin for thousands of people. "Our facilities are designed to produce insulin crystals in multiple metric-ton quantities," Walsh says.
The E. coli have humble beginnings. Small tubes of the bacteria have been stored in a freezer at minus 70 degrees Celsius (minus 94 degrees Fahrenheit) for decades. Lilly produced a granddaddy batch of E. coli, now referred to as the "master cell bank," sometime in the 1980s. It has gone on to seed every batch of Humulin to this day. Whenever Lilly wants a fresh stash of Humulin, workers go to the freezer, pull out a tube from the master cell bank, thaw it out, and stimulate the bacteria to grow.
Starting with a mere half gram of bacteria, the microorganisms begin to replicate prodigiously, doubling their numbers every 20 minutes or so. Once a tube gets too crowded, the bacteria are moved into larger and larger domiciles, from flask to bigger flask and from tank to bigger tank. All the microorganisms need to flourish is a source of water, sugar, salt, and nitrogen, which their handlers generously supply. In addition, the bacterial broth contains an additive that helps keep any contaminating microorganisms at bay, says Walsh. Typically, the E. coli are engineered to be resistant to a particular antibiotic, such as ampicillin, so that adding ampicillin to a broth will kill off everything but the prized protein producers. After several days of reproduction, the bacteria are now ready to start their real job—making insulin.
Until this point, the bacteria have been kept from making insulin by a repressor protein that sits near the insulin gene. To jump-start insulin production, the researchers free up the insulin gene by adding a chemical called an inducer to the giant vat of teeming bacteria. The critters promptly begin to churn out insulin, holding the protein in clumps inside themselves. After a fixed period, typically a few hours, it's time for the harvest and the hard work of isolating the insulin from mounds of bacterial trash.
The first step in the purification scheme is to separate the bacteria from the broth. That's done with a centrifuge, a machine that spins very fast, forcing the bacteria into a pellet at the bottom of a vessel. The broth is then removed and replaced with a liquid containing a substance that breaks down cell membranes, helping release the insulin from its bacterial prison.
At this point, the insulin still isn't actually insulin. It's "proinsulin," a longer inactive precursor of insulin. Insulin makers use an enzyme to carve out a section of proinsulin, leaving behind just the 51 amino acids of insulin proper. (The part that is snipped out is called C-peptide. It's a hormone in its own right, and doctors sometimes measure it in the blood of people with type 1 diabetes to see whether their bodies are still making some insulin.)
The next phase of industrial purification involves an array of giant columns made of a clear material and filled with an opaque resin. Except for their size, the columns look much like standard laboratory equipment.
When describing the girth of an industrial purification column, a smiling Lilly scientist stretched his arms out widely, bringing to mind an insulin-producing Parthenon. The columns are filled with various substances designed to separate insulin from other molecules based on differences in their electrical charge, acidity, size, and other characteristics. The insulin emerges from the columns alone.
At the end of its march through the mammoth columns, the insulin is quite pure. Yet, during processing, the insulin's chain of amino acids gets all tangled, rendering it inactive. To fix this, the researchers use yet another special mix of enzymes to iron out the wrinkles and get insulin into its proper form.
The final step before the insulin is ready for packaging is crystallization. The insulin is mixed with zinc, which helps it form stable crystals, and dried until it's nothing but a powder of glistening crystals. In due time, the crystals can be rehydrated in solution and poured into the vials, cartridges, and pens that are shipped around the globe.
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