When the patent of a brand-name, marketed drug\nexpires, new, generic products are usually offered. Smallmolecule\ngeneric and originator drug products are expected\nto be chemically identical. Their pharmaceutical similarity\ncan be typically assessed by simple regulatory criteria such\nas the expectation that the 90 % confidence interval for the\nratio of geometric means of some pharmacokinetic parameters\nbe between 0.80 and 1.25. When such criteria are satisfied,\nthe drug products are generally considered to exhibit\ntherapeutic equivalence. They are then usually interchanged\nfreely within individual patients. Biological drugs are complex\nproteins, for instance, because of their large size, intricate\nstructure, sensitivity to environmental conditions,\ndifficult manufacturing procedures, and the possibility of\nimmunogenicity. Generic and brand-name biologic products\ncan be expected to show only similarity but not identity in\ntheir various features and clinical effects. Consequently, the\ndetermination of biosimilarity is also a complicated process\nwhich involves assessment of the totality of the evidence for\nthe close similarity of the two products. Moreover, even\nwhen biosimilarity has been established, it may not be\nassumed that the two biosimilar products can be automatically\nsubstituted by pharmacists. This generally requires\nadditional, careful considerations. Without declaring interchangeability,\na new product could be prescribed, i.e. it is\nprescribable. However, two products can be automatically\nsubstituted only if they are interchangeable. Interchangeability\nis a statistical term and it means that products can be\nused in any order in the same patient without considering the\ntreatment history. The concepts of interchangeability and\nprescribability have been widely discussed in the past but\nonly in relation to small molecule generics. In this paper we\napply these concepts to biosimilars and we discuss: definitions\nof prescribability and interchangeability and their statistical\nimplementation; the relation between bioequivalence\nand interchangeability for small-molecule drug products;\nregulatory requirements and expectations of biosimilar\nproducts in various jurisdictions; possible statistical\napproaches to establish the similarity and interchangeability\nof biologic drug products; definition of other technical terms\nsuch as switchability and automatic substitution. The paper\nwill be concluded with a discussion of the anticipated future\nuse of interchangeability of biological drug products
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