Both the European Medicines Agency (EMA) and the US Food and Drug Administration (US FDA) have drafted reference papers and guidance’s for the industry for several types of NBCDs, e.g. for iron nanoparticles products. Also regulatory science initiatives have addressed lacking investigations.[1][2][3][15][16][17][18][19] For the comparability exercise the question stays to evaluate the totality of evidence for enough similarity of such test drugs with the reference product to conclude of the extent of comparability and its impact on use. Currently, the FDA follows a case-by-case approach for the evaluation of NBCD follow-on products, which is iterative, adaptive and flexible but also more general.