Impact of variability on the choice of biosimilarity limits in assessing follow-on biologics.

With larger variation in biological products compared with small molecular drugs, it is suggested that the assessment of biosimilarity of follow-on biologics (FOBs) should take variability into consideration in addition to average as standard in bioequivalence tests in small molecule drugs. Recent research on assessing variability in biosimilarity of FOBs has focused on direct assessment of variances, individual biosimilar index aggregating average and variability, and comparison of the entire distributions. However, the choice of biosimilarity limits for evaluating FOBs has not been investigated in the literature. In this article, we first explore the impact of variability on biosimilarity limits for the average biosimilarity assessment. On the basis of the derived relationship between variability and biosimilarity limit that result in the same power given all other parameters fixed, we propose several scaled biosimilarity limits to incorporate highly variable biological products.