A timely recommendation to the european medicines agency and the FDA on rationalizing comparative clinical efficacy testing of biosimilars

Biosimilars, copies of biological therapeutic proteins, for which regulatory guidelines were established 19 years ago in the EU and 15 years ago in the US, based on the understanding that comparative testing with reference products should reduce the time and cost burden for their approval, enabling their accessibility, availability, and affordability. So far, the EMA has approved 86 biosimilars comprising 27 molecules, including peptides, and the US has approved 57 biosimilars representing 17 molecules, excluding peptides. Except in a few instances in the EU, the cost of these products to patients remains high, and the choice of more than 100 available biological drugs still needs to be fulfilled due entirely to their high development cost, primarily attributed to comparative clinical efficacy testing (CCET). While the MHRA has concluded that such trials are unnecessary, the EMA is getting ready to modify the basis of these trials, and it is anticipated that the US FDA will follow the plan, finally making biosimilars accessible. This paper outlines the scientific rationale behind the futility of CCETs and advises the EMA to include these recommendations in a forthcoming report to resolve the fate of CCETs.