Laszlo Endrenyi
University of Toronto, Canada
Title: Interchangeability, switch ability and substitution of biosimilars drug products
Biography
Biography: Laszlo Endrenyi
Abstract
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.