In rapidly changing markets, how best to illustrate interchangeability of biosimilars?

Article title: Interchangeability of Biosimilars: What Level of Clinical Evidence is Needed to Support the Interchangeability Designation in the United States?

Citation: Alvarez DF et al. BioDrugs 2020;34:723–32

Publication date: September 2020

Abstract published: August 2021
Biosimilars are approved as highly similar to, but not necessarily interchangeable with, their reference biologic. As markets increasingly move towards accommodating lower-cost biosimilars and best-value biologics, how can clinicians be sure about safe switching?

Biologics are complex molecules manufactured using purified extracts from genetically engineered microorganisms and patented by the innovator company – generally for 10 years. After patent expiration, other manufacturers can market follow-on copies of the originator biologic, called biosimilars. Biosimilars cannot be considered identical to biologics due to differences in manufacturing processes – only “highly similar” – with no clinically meaningful differences.

In the USA,  interchangeability is determined by individual state laws, implying that biologics can be switched for biosimilars at pharmacy level without prescriber intervention. To be considered interchangeable, an applicant drug must demonstrate biosimilarity and evidence that it can be expected to produce the same clinical effects as the originator in any given patient and that switching would have no detectable adverse consequences.

Since biosimilarity does not automatically imply interchangeability, a recent study examined design features intended to support both regulatory designations simultaneously – incorporating elements to establish (1) biosimilarity and (2) interchangeability: (1) study participants are enrolled in a randomized, head-to-head comparator trial investigating safety and efficacy of the biosimilar versus originator; (2) participants are re-randomized in a switching study, receiving the biologic and biosimilar for at least one period of exposure each. Assessment should focus on the drugs’ pharmacokinetics and immunogenicity profiles.


The researchers concluded that performing switchover studies may not be absolutely necessary to support a designation of interchangeability. Multiple switches between biologics and biosimilars occur in routine daily clinical practice, and accumulating experience of this approach can provide a wealth of “real-world” data. In future, prospective registry studies and clinical trials (with real-world component) may obviate the need for dedicated switchover studies to establish interchangeability status.

Key takeaway

There are multiple instances of ‘real-world’ switches between biologics and biosimilars occurring in daily practice. Collating this data would provide a wealth of information relating to switching to aid in the designation of interchangeability of a given biosimilar.