Biologics and Biosimilars

The assessment of and conditions for the interchangeability of biological and small-molecule drug products are very

different. Small-molecule drugs are well defined and can be exactly reproduced. If their products, brand-name and

generic, are declared to be bioequivalent then they are (most frequently but not always) therapeutically equivalent and can

be substituted and interchanged. In contrast, biological drugs are structurally and functionally complicated, can be only

imitated but not identically reproduced, are sensitive to various environmental and manufacturing conditions, are subject

to biological and immunological influences. Consequently, only high similarity but not equivalence can be demonstrated, in

various respects, between the marketed and new products. However, even the stated bio similarity of two products does not

enable their interchangeability in terms of switching and alternating. For this, additional conditions must be satisfied. There

has been no agreement on these conditions among the various jurisdictions. Legislation in the United States, and also FDA,

has set general principles. The European EMA has issued biosimilarity guidelines for several drug products. The latter permit

in some cases possible interchangeability even though the issue is under the judgment of the member states. It is desirable to

develop a general, scientific basis for the evaluation of interchangeability of biological drug products. Suitable study designs are

considered, an approach for the assessment of switching and alternating across multiple domains is presented, and a possible

criterion for the interchangeability of biological products is described.