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The unique manufacturing, intellectual property protection, and market potential of biologic drugs has been described previously in this chapter. The remainder of this chapter will review why biologics are gaining a more prominent place in medicine, and what characteristics they possess that small molecule drugs do not or cannot. Small molecule drugs currently make up more than 90% of pharmaceutical therapeutics used for treating disease.¹¹ They are relatively easy to develop and suit their intended purposes reasonably well; a small molecule can be an effective enzyme inhibitor or receptor ligand, for example. However, there are noteworthy clinical limitations with this therapeutic approach. Typically, for a small molecule to be effective, it needs to be enveloped or be reasonably close to its target protein or transporter; the better the fit, the stronger the affinity and this often relates to how significant the drug's impact is on the human body. Small molecules bind to receptors in similar fashion and when doing so they compete with the natural ligand, which results in agonist, antagonist, or partial agonist/antagonist activity. Most cellular functions in the body, however, are mediated by proteins interacting with other proteins.¹¹

A major limitation of traditional small molecule drugs is that they simply fit into a specific destination that results in a biological perturbation, but do not necessarily receive feedback from the body after the drug change has taken place. This can be helpful for inhibiting a bacterial infection or other processes that require one‐directional activity, but it can result in unpredictability for more complex biological processes. For example, a small molecule beta‐blocker such as propranolol will continue blocking beta‐adrenergic receptors regardless of whether a patient is sitting, standing, or exercising. Another issue is that small molecule chemicals are not always site‐specific and off‐target systems can be affected. Nonselective beta‐blockers are contraindicated in some asthmatic patients for this reason; in addition to relaxing smooth muscle in the heart, they can also affect beta receptors in the lung resulting in bronchoconstriction.

Conversely, as biologic drugs can mimic normally existing (endogenous) proteins or protein interactions, they can receive feedback from biological systems in the body while producing their therapeutic activity. Biologic drugs can act more specifically and are often far more potent than small molecules. They more closely resemble naturally occurring proteins within the body and can be more effective in treating diseases. How closely a biologic drug resembles human proteins can have significant impact to its safety and efficacy. Biopharmaceuticals can generally be described by three major areas of their use²:

 Prophylactic/ preventive use such as vaccines

 Therapeutic use such as antibodies or enzymes

 Replacement use such as with growth factors or hormones