biologics vs. biosimilars

Oral drugs are almost always chemical, molecular, or small molecule drug. This kind of drug is typically synthesized in a chemical laboratory. A chemical drug is normally prepared as a pure or essentially pure homogeneous material that is then mixed with other materials to create the formulated drug that is taken by the patient. Most all oral drugs are chemical drugs, and very many injected, inhaled, and topical drugs are also chemical drugs. How about biological drugs? Biological drugs, or biologics, are made by living organisms, often through microbial, cell, or tissue cultures. Biological drugs include vaccines, antibodies, and some proteins. Biologics are not generally obtained as a pure substance, and the biologically active substance likely has some variability in its structure and composition. For example, components in the biological drug may have varying degrees of glycosylation, which is controlled by the biological organism.
The term generic drug refers to copies of a branded or reference chemical drug. Chemical drugs are normally fairly easy to copy. The structure is well defined, so it is relatively easy to duplicate the material. Chemical synthesis is not easy, but it is typically well understood. The formulation of chemical drugs, especially oral drugs, can often by imitated without undue effort. Copies of biologics are not called generics. They are called biosimilars. Copying a biological drug is much more difficult because the identity and composition of the biological drug is less clear. This lack of clarity poses a challenge to the creation of biosimilars.
If you want to create a generic of a biologic drug, more properly a biosimilar, then you need to establish bioequivalence of the new biosimilar to the branded or reference biologic. That is very hard since chemical duplication is impossible because chemical characterization of the reference material is likely incomplete. Furthermore, exact cell line and incubation conditions for the biosynthesis may also not be possible to completely replicate. Because a biosimilar will not be identical the reference biologic, you cannot treat biosimilars like generics. With generics, you assume that since the two substances are the same that they will show the same safety and efficacy. Establishing the bioequivalence of a biosimilar requires much more functional testing – testing for the safety and efficacy of biosimilar material. Bioequivalence trials are more costly, time-consuming, and rigorous for biosimilars.