Biopharmaceuticals: Medicines Made by Living Cells

What is a biopharmaceutical?

A biopharmaceutical (also called a biologic) is a medicine made by living cells. Most are proteins, or are made from proteins.

Compare two kinds of drug:

• Small-molecule drug (for example aspirin): few atoms, made by chemical reactions in a factory.
• Biopharmaceutical (for example insulin): thousands of atoms, folded in a special 3D shape. The shape does the job, so it must be exact. Cells are good at building such shapes.

Because a protein can break in the stomach, most biopharmaceuticals are given by injection.

Step 1: put the human gene into a host cell

A gene is the recipe for one protein. To make human insulin in a microbe we use recombinant DNA technology (see Recombinant DNA technology):

1. Get the human insulin gene.
2. Cut open a plasmid (a small ring of DNA found in bacteria) with a molecular scissor, an enzyme.
3. Join the gene into the ring with another enzyme, a molecular glue.
4. Put the new ring into the host cell.

Host cells can be bacteria (fast, cheap), yeast (can add sugar tags) or mammal cells (best for large proteins such as antibodies). Choosing the host is a key decision.

Step 2: grow the cells in a fermenter

A fermenter (or bioreactor) is a closed steel tank. It gives the cells what they need: food (sugar, salts, amino acids), air, the right temperature (about 37 °C for many hosts) and the right pH. A stirrer mixes everything.

The tank is made germ-free (sterile) before use. One stray germ can spoil the whole batch.

Cells divide again and again. In a good tank bacteria may double every 20 to 30 minutes, so one cell becomes millions in a day. Every cell makes drug, so more cells means more medicine. Scientists watch the temperature, pH and oxygen all the time.

Step 3: purify, test and fill

After growing, the tank liquid holds cells, leftover food and many other proteins. This is the downstream processing:

1. Separate the cells (filter or spin in a centrifuge).
2. Purify the drug with columns that hold the drug or the junk (chromatography).
3. Test purity, strength and germs.
4. Fill sterile vials and store them cold.

Purity is very important. A tiny leftover of host protein can make the patient's body react. Regulators in each country check the factory and each batch before the medicine is sold.

Kinds of biopharmaceuticals and why they matter

• Insulin: controls blood sugar in diabetes.
• Vaccines (some are made from a harmless piece of a germ): train the body to fight a disease.
• Monoclonal antibody drugs: lock on to one target, used for some cancers and arthritis (see Monoclonal antibodies).
• Growth hormone and clotting factors: for children who grow slowly and for haemophilia.

Why use cells? The drug is the exact human protein, supply is large, and there is no risk of animal-organ infections. Limits: they are costly to make, need cold storage and strict clean rooms, and a few patients make antibodies against them.

Try it: spot the biologic

Predict, then check. In the 3D free play, pick Bacteria and set 6 hours. Predict how many times it multiplies, then read the tag (6 ÷ 0.5 = 12 doublings, about 4 000 times). Now pick Mammal cells at 6 hours and compare. At home: look at a medicine strip or the pack of a vaccine or insulin pen. Does the label say "recombinant" or "biological"? Is it kept in the fridge? That is a clue that it is a protein drug.

Key formulas and definitions

• Biopharmaceutical = drug made by living cells (mostly protein)
• Gene in → Ferment → Purify (G-F-P)
• Cells after n doublings = starting cells × 2ⁿ
• Number of doublings = time ÷ doubling time

Worked examples

Common mistakes

• Thinking all medicines are made by living cells. Many (like aspirin) are made by chemists.
• Forgetting to purify. A drug straight from the tank is not safe to inject.
• Thinking a bacterium naturally makes human insulin. It makes it only because we added the human gene.
• Mixing up fermenter size with doubling time: a bigger tank does not make cells divide faster.