Individual Bioequivalence and Interchangeability: Graphical Approaches
Paul Hshieh, FDA/CBER  *Tie-Hua Ng, FDA/CBER 

Keywords: Generics, Biosimilars, individual bioequivalence, interchangeability, Bland-Altman plot, Q-Q plot, graphical approach

Hshieh and Ng (2015; JSM Proceedings, Biopharmaceutical Section, 1377-1384) proposed a new “procedure” in assessing the agreement of a new method to an old method using three graphical approaches: scatter plot, Bland-Altman plot and Q-Q plot. In this procedure, subjects are measured twice using the Old method (Old1, Old2) and once using the New method (New). In each graphical approach, the plot of Old1 vs. Old2 is used as a norm in which the plots of New vs. Old1 and New vs. Old2 can be compared with. If the new method is comparable to the old, then the plots of New vs. Old1 and New vs. Old2 should each appear similar to the plots of Old1 vs. Old2.

In this presentation, similar approaches are used to assess (i) individual bioequivalence of a generic drug and (ii) interchangeability of a proposed biosimilar product to a Reference. Here, the Reference corresponds to the Old method and the generic drug (or the proposed biosimilar product) corresponds to the New method. Crossover design is proposed and simulated and real data are used to illustrate these graphical approaches.