ABSTRACT
Tetrahedron concept While Europe has been approving biosimilars for several years, the approach taken to approve these products has been more conservative and less structured; now that the FDA has allowed biosimilars with greater clarity, the path to biosimilar approval will change signicantly across the globe. An evidence of this suggestion is found in the recent EMA revision of its guidelines, bringing them in line with the thinking of the FDA, to allow obviating clinical trials in patients, if a scientic basis for the “safety, quality, and efcacy” can be justied without testing in patients. As I discussed in Chapter 1, the key denitions to dene critical attributes describing biosimilars are different among the agencies. The FDA does not use “quality” and suggests the use of “effectiveness” and not “efcacy.” These subtle differences have signicant meanings. The U.S. FDA has used three keywords to describe biological products: safety, purity, and potency. While the same terms are used in the demonstration of biosimilarity, there is one signicant gap in this de- nition. For a new molecular entity, purity, potency, and safety are characterization steps, not similarity testing steps; with biosimilars, every attribute is tested against a reference standard. Therefore, there is a need to add a fourth classication of attributes, IDENTITY, to the existing list of safety, purity, and potency. And this allows us to create a tetrahedron, wherein each of these categories of attributes is equally important, and must be checked off for similarity to demonstrate overall biosimilarity to qualify approval under the 351(k) statute. Figure 5.1 shows the tetrahedron of biosimilarity.
