The evaluation of the similarity of follow-on biologics (FoB) involves differing approaches of calculations and study conditions from those applied for determining the bioequivalence (BE). Parallel group rather than crossover designs are used. Total variation is important and not just intraindividual variation. Still, a procedure applied for assessing the BE of highly-variable small molecules could be considered also for determining the similarity of FoB products. Standardized comparisons of metrics have useful properties. They yield acceptances which are much higher than contrasts without standardization. Their producer risks are independent of the variability. They have also useful clinical interpretations. The approach should be further investigated for the quantitative comparison of FoBs.