The Development Pathway for Biosimilar Biotherapeutics

Many physicians have experience using generic drugs in their practice. Generics tend to be small molecules with a relatively simple structure and are identical to licensed reference products. Generic compounds typically are synthesized using organic medicinal chemistry. Variations in the manufacturing process are unlikely to have a major impact on the final product, an outcome that is verified through analytical characterization of the generic. A biosimilar biotherapeutic is a protein. Biosimilar products are quite different from generic drugs. A biosimilar has similar quality, safety, and efficacy to a licensed reference product, but it is not necessarily identical to the reference product with regard to these properties.[1] In contrast to generic drugs, biosimilars tend to have complex structures and may differ from the reference product in their primary amino acid sequence and other features such as glycosylation and PEGylation that alter their tertiary structure (i.e., protein folding) as well as their immunogenicity.[2] These differences arise from the manufacturing process, which tends to be much more complex than that of generic drugs. Typically, a biosimilar protein is synthesized by transfecting a target cell with a DNA sequence that encodes the desired product. Often, transfected mammalian cells are required to produce complex proteins, but these cells typically have lower yields than bacterial hosts. The initial product must be purified to remove undesired proteins. As one might expect, the use of different expression systems can be associated with different post-translational protein modifications.