Case studies are presented based on a review of European Public Assessment Reports from July 2012 to July 2019 to illustrate complex situations when assessing the totality of data during marketing authorization procedures, i.e. how to weigh conflicting results from different parts of the comparability exercise.

The pharmacokinetic study is emerging as a major gatekeeper in the clinical biosimilarity exercise, a hurdle that needs to be overcome and all results fully justified before further clinical data can be deemed acceptable.

The experience acquired with each biological product class, together with advances in terms of characterization techniques and progress in understanding pharmacology and disease pathogenesis, have paved the way towards reduction of clinical data requirements and are expected to continue doing so.