Biosimilar

Why "similar" and not "same"

A small-molecule generic can be chemically identical to its reference: same molecule, demonstrated by analytical chemistry plus a bioequivalence study. Biologics are produced by living cells and are large, heterogeneous and sensitive to process. Two batches of the originator's own product are not identical to each other.

"Identical" is therefore not an achievable standard. The regulatory question becomes whether remaining differences are clinically meaningful — and answering it takes a different evidence structure entirely.

The inverted evidence pyramid

For a new drug, clinical trials carry the weight. For a biosimilar, the foundation is analytical: extensive structural and functional characterisation against the reference, across many lots. Clinical work is confirmatory, sized to detect differences rather than to re-establish efficacy.

This inversion is deliberate. Analytical methods are more sensitive to the differences that matter than a clinical endpoint would be, and repeating full efficacy trials would be both uninformative and ethically questionable.

Interchangeability is a separate question

In the US, biosimilar and interchangeable are distinct designations. Interchangeability permits substitution at the pharmacy without the prescriber's involvement, and historically required additional switching data. Most other regulators never created the distinction, treating substitution as a prescribing-practice matter instead.

Why uptake disappointed

Biosimilars did not reproduce the generic price collapse. Development costs tens to hundreds of millions rather than low millions, so fewer entrants appear per molecule. Manufacturing requires biologics capacity. Originators defend with patent thickets, formulation changes and rebate structures tied to formulary position. The result is meaningful but far shallower discounting than small-molecule generics deliver.