Extrapolation: Experience gained from original biologics.

ABSTRACT

Biologicals undergo modifications throughout their commercial lifecycle. Major changes can unintentionally magnify their inherent physicochemical variability. Although trials comparing the pre- and the post-change versions have been requested occasionally, analytical comparison is the most sensitive approach to anticipating clinical equivalence. Therefore, it may be concluded, by means of 'extrapolation', that non-identical versions of a given biologic will behave equally in all indications. Despite the lessons learned with original biologics, there are still controversies around the approval of biosimilars through extrapolation. Here, a comprehensive analysis of scattered information allows for an account of cases of original biologic versions approved in some indications with no patient trials involved. Healthcare professionals can be reassured that inasmuch as extrapolation has proven valid for new versions of original biologics, the same holds for biosimilars.