By Tom Ricci
The commercial drug pipeline has made a dramatic shift from conventional small-molecule drugs to biologic-based pharmaceuticals in the past five years. This new class of protein-based pharmaceuticals is believed to be inherently safer than small molecule drugs and will enable longer innovator exclusivity because today it is not possible to create an identical copy of the drug, taking biogenerics out of the picture. And, while a few “biosimilar” drugs have been approved in Europe, they have not been approved in the U.S. and the FDA has yet to define regulations as to how biosimilar drugs will be evaluated and regulated.
Protein-based biomolecules have exhibited great promise for their therapeutic potential. However, they are much larger than small molecule compounds (up to 145,000 Daltons for biologics vs. 100 to 1,000 Daltons for small molecules) and very complex structurally. Even a small change to a single amino acid side chain on the protein can profoundly alter biological activity of the molecule. Because of their size and complexity, biologic drugs are difficult to define in molecular terms and can be inconsistent in their exact composition. This leads to difficulties in the assurance of product quality in terms of safety and efficacy.
Protein therapeutics differ from small molecules in several ways: They may contain intrinsic infectious agents, aseptic techniques are required during production; they usually are heterogeneous in composition; they may contain numerous process and product-related impurities; changes in the manufacturing process can cause changes in product composition; and their exact structure may be unknown.