Biologics vs Small Molecule Drugs

What are Biologics?

According to the US FDA, biological products include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins.

Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues.

Biologics are isolated from a variety of natural sources - human, animal, or microorganism - and may be produced by biotechnology methods and other cutting-edge technologies. Gene-based and cellular biologics, for example, often are at the forefront of biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available.

How do biological products differ from conventional drugs?

1. Conventional Drugs are often small molecule compounds synthesized by chemists in large factories using other chemicals as building blocks. Their molecular structures are well defined and relatively simple. Aspirin, for example, contains just 21 atoms (C9H8O4).

Biologic drugs are a different story. This class of medication is not synthesized chemically – instead they are isolated directly from living organisms, such as genetically engineered microbes or mammalian cell cultures.

2. Biologics are typically much larger molecules than those found in conventional pharmaceuticals, and in many cases their exact composition is unknown (or even unknowable). You’re unlikely to find biologic drugs in tablet form – they tend to be delicate molecules that are happiest in liquid solution.

Therefore, for biologics, "the product is the process." As the finished product cannot be fully characterized in the laboratory, manufacturers must ensure product consistency, quality, and purity by ensuring that the manufacturing process remains substantially the same over time.

3. Biological products also tend to be heat sensitive and susceptible to microbial contamination. Therefore, it is necessary to use aseptic principles from initial manufacturing steps, which is also in contrast to most conventional drugs.

Here is a good report on the differences between conventional drugs and biopharmaceuticals presented by a Novartis scientist.

I find it quite interesting that biologic drugs have similar "me-too" versions, called biosimilars, as generics to small molecule innovator drugs.

The manufacturing process of biologics is very complex and takes more time and resources.