The Power of Biologics

Since the 1980s, Amgen has been revolutionizing treatment for patients with serious illnesses worldwide by recreating human proteins into biologic medicines.

A biologic is a large molecule which is made in living cells by adding a piece of DNA to a cell. The cell then either copies or translates the DNA piece into a protein which becomes the biologic medicine. Biologic medicines include therapeutic proteins and monoclonal antibodies (mAbs). They are often 200 to 1,000 times the size of a small molecule or chemical drug and are far more complex structurally. Due to both their large size and sensitivity, biologic medicines are almost always injected into the patient’s body.


The foundation of biologic medicines lies in recombinant DNA technology, which involves genetically engineering a cell. The technology to genetically engineer DNA in the cells is intricate, sensitive and often specific to a particular medicine. For instance, unlike small molecule drugs and generics that are manufactured via pure chemical synthesis, biologic medicines undergo several post-translational modifications when manufactured in living cells, meaning changes are made like additions of sugars to the protein structure. Consequently, these post-translational modifications introduce variability among biologics. 

Biologics are also highly sensitive to things like temperature and pH, making them more difficult to characterize and produce on a large scale. Even minor alterations may lead to changes in cell behavior and differences in the structure, stability or other quality aspects of the end product. Any of these differences have the potential to affect the treatment’s safety, efficacy and shelf life, and to increase the risk of an unwanted immune response. 1

 

Amgen’s Heritage in Developing Biologics

Fu-Kuen Lin, a research scientist at Amgen, was the first to clone a gene for a complex biologic, erythropoietin, in 1983.2 Amgen and Lin received the 1995 Discoverers Award from Pharmaceutical Research and Manufacturers of America for the development of the first man-made injectable version of erythropoietin.3

Since the discovery of a cloned copy of erythropoietin, Amgen has continued to develop innovative biologic medicines that have changed the way we treat cancer, rheumatoid arthritis, osteoporosis and other serious illnesses. Examples of other biologic medicines include vaccines, blood components, insulin and monoclonal antibodies (mAbs), all of which have been instrumental in treating millions of patients with serious diseases worldwide.

Comparison of Molecular Mass of Small Molecule (Chemical) Drugs Versus Large Biologics

GCSF: Granulocyte Colony-Stimulating Factor; HGH: Human Growth Hormone
EPO: Erythropoiesis-stimulating agent; mAbs: monoclonal Antibodies

Definitions

Biologic Medicine

A biologic medicine, often referred to as a “large molecule drug,” is made in genetically modified cells. Biologic medicines include therapeutic proteins, DNA and monoclonal antibodies (mAbs). Biologics have been instrumental in treating serious diseases like inflammatory bowel disease (IBD), rheumatoid arthritis, psoriasis, hepatitis C, diabetes and various cancers. Commonly known biologics include Herceptin®, a medicine used to treat HER2+ breast cancer.

Small Molecule Drugs (Chemical Medicines)

Small molecule drugs are manufactured through chemical synthesis by combining specific chemical ingredients in a well-defined and predictable process. They have smaller molecular weight (<900 Daltons) with a well-defined molecular structure that is independent of the manufacturing process.5,6  Commonly known small molecule drugs include Aspirin, Lipitor®, Zocor® and Prilosec®.

Glossary
Cancer

Biotechnology has contributed to significant advances in cancer treatment, including hormone therapies, biologics and targeted therapies such as monoclonal antibodies (mAbs) that have revolutionized oncology supportive care for immune-compromised patients on chemotherapy.

Inflammation

With the advent of biologics, treatment of rheumatoid arthritis (RA) has transformed from managing symptoms to aiming for disease remission by inhibiting specifically targeted biochemical pathways of inflammation.4