Biologic Logic

Biogen scientists in Research Triangle Park engineer biologic medicines, which are produced by living cells, making them a challenge to develop and manufacture, but it is a process with amazing results.

RESEARCH TRIANGLE PARK — Cell culture engineer Brandon Moore removes the insulating wrap from a large glass jar that has about a half dozen plastic tubes attaching to its top. The sound of whirring pumps fills this lab at Biogen in Research Triangle Park. A clear look at the contents of the jar reveals a brown liquid, about the color of coffee with heavy cream, and it is foaming.

“This is the cell soup and that big motor up there is a kind of giant blender,” explains Moore, a cell culture engineer with Biogen, as he peers closely at the contents of his jar. “There’s mostly liquid being added to the jar so its just spinning the cells around, agitating them, to make sure they are as evenly distributed as possible.”

The container is a bioreactor—kind of a scientific super crock pot. There are dozens of them, of varying sizes, in this lab. Moore is in charge of this experiment, so you could say he’s a cell chef.

“What cells do best is divide and we want to make sure they are in the correct environment to divide,” says Moore. “So this bioreactor gives a cell everything it needs to grow and live and it’s really just like the cells in our bodies. We need oxygen, we need nutrients, and we need the correct pH, which is not too acidic and not too basic.”

Biogen operates one of the largest cell culture facilities in the world in Research Triangle Park. It is a science company but it is also a manufacturing company. Biogen produces biologic molecules, which are composed of sugars, proteins, nucleic acids, or other complex combinations. Then those molecules are turned into medicines.

While many medicines, such as aspirin, are simple chemical combinations produced in a lab, the molecules of biological medicines are large and complicated. So researchers turn to nature to do the work. In the world of biologics, it’s the cells in the soup that make the products.

“The drug is not the cell in the soup, rather the cells make the drug and then throw it out of their membranes in the media,” says Moore, as he waves his hands around the jar with brown liquid. “This jar contains the cells, the culture they live in, and the drug they secrete that we want. So what we end up with is a mix of cells and proteins that we don’t want, and proteins that we do want.”

Think of a recipe.

Once a molecule is identified to treat a disease, cells must be convinced to make it because it is too complex to be produced in a lab.

So the genome of the cell is modified to produce the desired molecule or future medicine. Meanwhile, engineers prepare a cell matrix, or cell soup, which will keep the cells alive as well as protect the special molecules that are being produced.

Once the cells are making and then secreting the special cells into the matrix, the mix must be purified to retrieve the desired cells.

If it all works, the process is expanded to increase production. What started in a dish in a lab is gradually increased to thousands of gallons, while still having the desired therapeutic effect on a disease.

“In the midst of all this, we have to make sure that the product quality attributes are always the same, so the molecule that the cells are producing remains the same as what we say it is based on these attributes in a certain range,” says Mark Chen, a manufacturing scientist with Biogen.

The special cells produced in small bioreactors are not enough to make the numbers of doses patients need as well as make Biogen a profit. So the cells are constantly being examined to see if they can produce more while still maintaining quality.

“Things change drastically as you scale up,” says Aeona Magliola, a chemical engineer with Biogen, who says there are so many ways you think of the scale, including the chemical environment. And then there’s the challenge of turning the molecule into actual medicine.

“So even after you purify the drug, you’ve got a few more challenges, including stability,” adds Magliola. “Because now the molecule is in a matrix that allows it to stay in an antibody formation, but it has to be in an environment where it is delivered to a human.”

And yet as difficult as it is, researchers say the process still amazes.

“We’re making a protein in a non-human host, and then purifying it and injecting it into a human,” says Moore. “And that body sees the protein and uses it to perform a healing function. It’s amazing.”


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