Table 1.

Differences in characterization and manufacturing of biologics and small-molecule drugs.¹

	Biologics (protein-based drugs)	Small molecules (chemically based drugs)
Properties
Size	Large	Small
Structure	Complex	Simple
Degradation mechanism	Complex	Precise and known
Variability	Heterogeneous product	Single, defined structure
Manufacturing	Unique bank of living cells Unlikely to achieve identical copy	Predictable chemical and reagent reaction Identical copy can be made
Characterization	Difficult to fully characterize	Easy to fully characterize
Stability	More sensitive to storage and handling conditions	Less sensitive to storage and handling conditions
Immunogenicity	Higher potential	Lower potential

¹Biologics are protein-based drugs and can be thousands of times larger than chemically based small-molecule drugs. The amino acid chains of biologics form complex multidimensional structures. Additionally, biologics may have variations in protein folding, subunit makeup, and posttranslational modification (e.g., glycosylation), whereas small-molecule drugs have well-defined chemical structures. Thus, biologics have a higher immunogenic potential than small molecule drugs and are more sensitive to storage and handling conditions ^1,4,5. Although small-molecule drugs can be fully characterized using current analytical procedures, it is much more difficult to fully characterize biologics because they comprise a heterogeneous mixture of related molecules ⁵. Manufacturing of biologics is more complex than that of small-molecule drugs, and differences in cell lines and manufacturing processes for biologics make it unlikely for different manufacturers to make identical copies of a biologic. In contrast, identical copies of small-molecule drugs can be synthesized through predictable chemical reactions.