Biosimilarity is not a transitive property: implication for interchangeability, naming and pharmacovigilance

Abstract

Current regulations do not require a given biosimilar to remain similar to its reference biological over time. However, two products that were initially deemed biosimilar or interchangeable could each undergo unique patterns of drift and evolution in their manufacturing processes (divergence), ultimately resulting in two products that would be no longer biosimilar. In cases where divergence in potency, safety and immunogenicity may be present, care should be taken with multiple switches between reference and biosimilar products: each time a switch occurs, the diff erence between products could be greater. Taking into account that post-marketing comparative biosimilarity validation is not required, drift, evolution and divergence may present greater challenges when assessing biosimilar. In a marketplace with multiple biosimilars of a given reference product and in the context of interchangeability with drift and divergence, pharmacovigilance systems should be strengthened.